MDedge Dermatology

The Diagnosis: Congenital Hemangioma

Surgical resection of the mass was performed at 4 months of age without complication (Figure 1). Histopathology revealed a lobular endothelial cell proliferation within a densely fibrotic stroma, multiple thin-walled vessels, and negative immunoreactivity to glucose transporter type 1 (GLUT-1)(Figures 2 and 3). Combined with the patient’s clinical history and findings on imaging (Figure 4), the most accurate diagnosis was a congenital hemangioma (CH). The mass was determined to be a noninvoluting congenital hemangioma (NICH).

A variety of vascular anomalies manifest in newborns and can be differentiated by the patient’s clinical history—particularly whether the lesion is present at birth or develops after birth. Imaging and histopathology of the lesion(s) may be utilized when clinical examination alone is not sufficient to make a diagnosis. Histopathology and immunohistochemistry further aid in differentiating the type of vascular lesion.

Overall, vascular anomalies are classified broadly into 2 categories based on their pathogenesis: tumors and malformations. Vascular tumors are composed of proliferating endothelial cells that have the potential to resolve spontaneously over time. Examples include CH, infantile hemangioma (IH), kaposiform hemangioendothelioma (KHE), and tufted angioma (TA). In contrast, vascular malformations (ie, arteriovenous malformations) are composed of dysplastic vessels with normal endothelial cell turnover and do not resolve without intervention.¹

Congenital hemangiomas are rare vascular tumors that are fully developed at birth. These tumors proliferate in utero, enabling prenatal detection via ultrasonography as early as 12 weeks’ gestation for large heterogeneous vascular masses.^2-4 Congenital hemangiomas are described as solitary, well-circumscribed, raised, violaceous lesions most commonly located in the head and neck region.^4-6 Histopathologically, they are characterized by lobules of proliferating capillaries surrounded by fibrous stroma and dysplastic vascular channels.^6,7

Congenital hemangiomas are categorized based on their postnatal involution patterns.2 Fetally involuting CH both develops and begins regression in utero and often is completely regressed at birth.⁸ Rapidly involuting CH begins regression in the first few weeks of life and usually is completely involuted by 14 months of age.6,9-11 Conversely, NICH does not regress, often requiring surgical excision due to functional and cosmetic issues.^12,13 Partially involuting CH is intermediary, beginning as rapidly involuting but not involuting completely and persisting as lesions that resemble NICH.^14-16 Although generally benign and asymptomatic, these tumors can cause transient thrombocytopenia and coagulopathy at birth, as seen in our patient.^17,18

Infantile hemangioma is the most common vascular tumor of infancy.^19-21 Although a precursor lesion may be present at birth, generally this tumor becomes apparent after the first few weeks of life as a solitary vascular plaque or nodule with a predilection for the head and neck.^22-25 Once it arises, IH quickly enters a period of rapid growth, followed by a period of slower continued growth, with most reaching maximum size by 3 months.²² Thereafter, IH enters a slow period of involution (range, 3–9 years)²⁶; more recent data suggest near resolution by 5 years of age.²⁷ Infantile hemangioma is categorized based on its depth in the skin and subcutaneous tissues and can be classified as superficial, mixed, or deep.^22,24,28,29 Superficial IH appears as a red plaque and may exhibit lobulation, while deep IH can be identified as flesh-colored or blue subcutaneous masses. Mixed IH may manifest with both superficial and deep features depending on the extent of its involvement in the dermal and subcutaneous layers. The pattern of involvement may be focal, segmental, or indeterminate.²⁴ In contrast, CH typically is a solitary vascular mass with prominent telangiectases, nodules, and radiating veins.⁶ Histologically, IH is composed of proliferative plump endothelial cells that form capillaries, and the lesion stains positively for GLUT-1, whereas CH does not.³⁰

Kaposiform hemangioendothelioma is classified as a locally aggressive vascular tumor that manifests either prenatally or in early infancy.³¹ It is described as a solitary, ill-defined, firm, purple plaque most commonly located on the extremities and retroperitoneum.^32-34 Histopathologically, these lesions are characterized by dilated lymphatic channels and irregular sheets or lobules of spindle-shaped endothelial cells infiltrating the dermis and subcutaneous fat.^33,35 In contrast to CH, KHE lesions show immunoreactivity to the markers podoplanin, lymphatic vessel endothelial receptor 1, and prospero homeobox 1 protein.^36,37 Notably, 70% of these tumors are complicated by the presence of Kasabach-Merritt phenomenon, a potentially life-threatening emergency that occurs when platelets are trapped within a vascular tumor, leading to the consumption of clotting factors, intralesional bleeding, and rapid enlargement of the tumor.³² The Kasabach-Merritt phenomenon manifests clinically as microangiopathic hemolytic anemia, severe thrombocytopenia, and disseminated intravascular coagulation. ³⁸ Although CH lesions also can be associated with thrombocytopenia and coagulopathy, they generally are mild and self-limited.¹⁸

Tufted angioma is a vascular tumor that arises within the first 5 years of life as firm violaceous papules or plaques, often with associated hyperhidrosis or hypertrichosis.^39,40 Although TA grows slowly for a period of time, it eventually stabilizes and persists, rarely regressing completely.⁴¹ These tumors share many similarities with KHE, and it has been suggested that they may be part of the same spectrum. 42 As with KHE, TA lesions show immunoreactivity to the markers podoplanin, lymphatic vessel endothelial receptor 1, and prospero homeobox 1 protein, which are negative in CH.^36,37 Although TA also can be complicated by Kasabach-Merritt phenomenon, the incidence is much lower (up to 38%).^43,44 As such, TAs tend to be recognized as more superficial benign lesions. However, they still can cause notable cosmetic and functional impairment and should be monitored closely, especially in the presence of associated symptoms or complications.

Arteriovenous malformation is a vascular lesion that results from errors during the embryonic development of vascular channels.⁴⁵ Although present at birth, it may not become clinically apparent until later in life. Arteriovenous malformations enlarge postnatally, and their growth is proportional to the developmental growth of the affected individual rather than the result of endothelial proliferation.⁴⁶ In infants, AVM may manifest as a faint vascular stain that can evolve over time into a pink patch associated with a palpable thrill during adolescence. ⁴ On Doppler flow imaging, AVMs are identified as fast-flow anomalies arising from an abnormal communication between high-pressure arterial systems and low-pressure venous systems without the presence of a capillary bed.⁴⁷ One of the differentiating factors between AVM and CH is that AVMs do not regress spontaneously and tend to have high recurrence rates, even with intervention. ⁴⁸ In contrast, CH can be categorized based on its postnatal involution pattern. Another distinguishing factor is that AVMs tend to be larger and more invasive than CHs.⁴⁶ Therefore, early diagnosis and intervention are crucial to prevent complications such as bleeding, seizures, or neurologic deficits associated with AVMs.¹

The Diagnosis: Congenital Hemangioma

Surgical resection of the mass was performed at 4 months of age without complication (Figure 1). Histopathology revealed a lobular endothelial cell proliferation within a densely fibrotic stroma, multiple thin-walled vessels, and negative immunoreactivity to glucose transporter type 1 (GLUT-1)(Figures 2 and 3). Combined with the patient’s clinical history and findings on imaging (Figure 4), the most accurate diagnosis was a congenital hemangioma (CH). The mass was determined to be a noninvoluting congenital hemangioma (NICH).

A variety of vascular anomalies manifest in newborns and can be differentiated by the patient’s clinical history—particularly whether the lesion is present at birth or develops after birth. Imaging and histopathology of the lesion(s) may be utilized when clinical examination alone is not sufficient to make a diagnosis. Histopathology and immunohistochemistry further aid in differentiating the type of vascular lesion.

Overall, vascular anomalies are classified broadly into 2 categories based on their pathogenesis: tumors and malformations. Vascular tumors are composed of proliferating endothelial cells that have the potential to resolve spontaneously over time. Examples include CH, infantile hemangioma (IH), kaposiform hemangioendothelioma (KHE), and tufted angioma (TA). In contrast, vascular malformations (ie, arteriovenous malformations) are composed of dysplastic vessels with normal endothelial cell turnover and do not resolve without intervention.¹

Congenital hemangiomas are rare vascular tumors that are fully developed at birth. These tumors proliferate in utero, enabling prenatal detection via ultrasonography as early as 12 weeks’ gestation for large heterogeneous vascular masses.^2-4 Congenital hemangiomas are described as solitary, well-circumscribed, raised, violaceous lesions most commonly located in the head and neck region.^4-6 Histopathologically, they are characterized by lobules of proliferating capillaries surrounded by fibrous stroma and dysplastic vascular channels.^6,7

Congenital hemangiomas are categorized based on their postnatal involution patterns.2 Fetally involuting CH both develops and begins regression in utero and often is completely regressed at birth.⁸ Rapidly involuting CH begins regression in the first few weeks of life and usually is completely involuted by 14 months of age.6,9-11 Conversely, NICH does not regress, often requiring surgical excision due to functional and cosmetic issues.^12,13 Partially involuting CH is intermediary, beginning as rapidly involuting but not involuting completely and persisting as lesions that resemble NICH.^14-16 Although generally benign and asymptomatic, these tumors can cause transient thrombocytopenia and coagulopathy at birth, as seen in our patient.^17,18

Infantile hemangioma is the most common vascular tumor of infancy.^19-21 Although a precursor lesion may be present at birth, generally this tumor becomes apparent after the first few weeks of life as a solitary vascular plaque or nodule with a predilection for the head and neck.^22-25 Once it arises, IH quickly enters a period of rapid growth, followed by a period of slower continued growth, with most reaching maximum size by 3 months.²² Thereafter, IH enters a slow period of involution (range, 3–9 years)²⁶; more recent data suggest near resolution by 5 years of age.²⁷ Infantile hemangioma is categorized based on its depth in the skin and subcutaneous tissues and can be classified as superficial, mixed, or deep.^22,24,28,29 Superficial IH appears as a red plaque and may exhibit lobulation, while deep IH can be identified as flesh-colored or blue subcutaneous masses. Mixed IH may manifest with both superficial and deep features depending on the extent of its involvement in the dermal and subcutaneous layers. The pattern of involvement may be focal, segmental, or indeterminate.²⁴ In contrast, CH typically is a solitary vascular mass with prominent telangiectases, nodules, and radiating veins.⁶ Histologically, IH is composed of proliferative plump endothelial cells that form capillaries, and the lesion stains positively for GLUT-1, whereas CH does not.³⁰

Kaposiform hemangioendothelioma is classified as a locally aggressive vascular tumor that manifests either prenatally or in early infancy.³¹ It is described as a solitary, ill-defined, firm, purple plaque most commonly located on the extremities and retroperitoneum.^32-34 Histopathologically, these lesions are characterized by dilated lymphatic channels and irregular sheets or lobules of spindle-shaped endothelial cells infiltrating the dermis and subcutaneous fat.^33,35 In contrast to CH, KHE lesions show immunoreactivity to the markers podoplanin, lymphatic vessel endothelial receptor 1, and prospero homeobox 1 protein.^36,37 Notably, 70% of these tumors are complicated by the presence of Kasabach-Merritt phenomenon, a potentially life-threatening emergency that occurs when platelets are trapped within a vascular tumor, leading to the consumption of clotting factors, intralesional bleeding, and rapid enlargement of the tumor.³² The Kasabach-Merritt phenomenon manifests clinically as microangiopathic hemolytic anemia, severe thrombocytopenia, and disseminated intravascular coagulation. ³⁸ Although CH lesions also can be associated with thrombocytopenia and coagulopathy, they generally are mild and self-limited.¹⁸

Tufted angioma is a vascular tumor that arises within the first 5 years of life as firm violaceous papules or plaques, often with associated hyperhidrosis or hypertrichosis.^39,40 Although TA grows slowly for a period of time, it eventually stabilizes and persists, rarely regressing completely.⁴¹ These tumors share many similarities with KHE, and it has been suggested that they may be part of the same spectrum. 42 As with KHE, TA lesions show immunoreactivity to the markers podoplanin, lymphatic vessel endothelial receptor 1, and prospero homeobox 1 protein, which are negative in CH.^36,37 Although TA also can be complicated by Kasabach-Merritt phenomenon, the incidence is much lower (up to 38%).^43,44 As such, TAs tend to be recognized as more superficial benign lesions. However, they still can cause notable cosmetic and functional impairment and should be monitored closely, especially in the presence of associated symptoms or complications.

Arteriovenous malformation is a vascular lesion that results from errors during the embryonic development of vascular channels.⁴⁵ Although present at birth, it may not become clinically apparent until later in life. Arteriovenous malformations enlarge postnatally, and their growth is proportional to the developmental growth of the affected individual rather than the result of endothelial proliferation.⁴⁶ In infants, AVM may manifest as a faint vascular stain that can evolve over time into a pink patch associated with a palpable thrill during adolescence. ⁴ On Doppler flow imaging, AVMs are identified as fast-flow anomalies arising from an abnormal communication between high-pressure arterial systems and low-pressure venous systems without the presence of a capillary bed.⁴⁷ One of the differentiating factors between AVM and CH is that AVMs do not regress spontaneously and tend to have high recurrence rates, even with intervention. ⁴⁸ In contrast, CH can be categorized based on its postnatal involution pattern. Another distinguishing factor is that AVMs tend to be larger and more invasive than CHs.⁴⁶ Therefore, early diagnosis and intervention are crucial to prevent complications such as bleeding, seizures, or neurologic deficits associated with AVMs.¹

The Diagnosis: Congenital Hemangioma

Surgical resection of the mass was performed at 4 months of age without complication (Figure 1). Histopathology revealed a lobular endothelial cell proliferation within a densely fibrotic stroma, multiple thin-walled vessels, and negative immunoreactivity to glucose transporter type 1 (GLUT-1)(Figures 2 and 3). Combined with the patient’s clinical history and findings on imaging (Figure 4), the most accurate diagnosis was a congenital hemangioma (CH). The mass was determined to be a noninvoluting congenital hemangioma (NICH).

A variety of vascular anomalies manifest in newborns and can be differentiated by the patient’s clinical history—particularly whether the lesion is present at birth or develops after birth. Imaging and histopathology of the lesion(s) may be utilized when clinical examination alone is not sufficient to make a diagnosis. Histopathology and immunohistochemistry further aid in differentiating the type of vascular lesion.

Overall, vascular anomalies are classified broadly into 2 categories based on their pathogenesis: tumors and malformations. Vascular tumors are composed of proliferating endothelial cells that have the potential to resolve spontaneously over time. Examples include CH, infantile hemangioma (IH), kaposiform hemangioendothelioma (KHE), and tufted angioma (TA). In contrast, vascular malformations (ie, arteriovenous malformations) are composed of dysplastic vessels with normal endothelial cell turnover and do not resolve without intervention.¹

Congenital hemangiomas are rare vascular tumors that are fully developed at birth. These tumors proliferate in utero, enabling prenatal detection via ultrasonography as early as 12 weeks’ gestation for large heterogeneous vascular masses.^2-4 Congenital hemangiomas are described as solitary, well-circumscribed, raised, violaceous lesions most commonly located in the head and neck region.^4-6 Histopathologically, they are characterized by lobules of proliferating capillaries surrounded by fibrous stroma and dysplastic vascular channels.^6,7

Congenital hemangiomas are categorized based on their postnatal involution patterns.2 Fetally involuting CH both develops and begins regression in utero and often is completely regressed at birth.⁸ Rapidly involuting CH begins regression in the first few weeks of life and usually is completely involuted by 14 months of age.6,9-11 Conversely, NICH does not regress, often requiring surgical excision due to functional and cosmetic issues.^12,13 Partially involuting CH is intermediary, beginning as rapidly involuting but not involuting completely and persisting as lesions that resemble NICH.^14-16 Although generally benign and asymptomatic, these tumors can cause transient thrombocytopenia and coagulopathy at birth, as seen in our patient.^17,18

Infantile hemangioma is the most common vascular tumor of infancy.^19-21 Although a precursor lesion may be present at birth, generally this tumor becomes apparent after the first few weeks of life as a solitary vascular plaque or nodule with a predilection for the head and neck.^22-25 Once it arises, IH quickly enters a period of rapid growth, followed by a period of slower continued growth, with most reaching maximum size by 3 months.²² Thereafter, IH enters a slow period of involution (range, 3–9 years)²⁶; more recent data suggest near resolution by 5 years of age.²⁷ Infantile hemangioma is categorized based on its depth in the skin and subcutaneous tissues and can be classified as superficial, mixed, or deep.^22,24,28,29 Superficial IH appears as a red plaque and may exhibit lobulation, while deep IH can be identified as flesh-colored or blue subcutaneous masses. Mixed IH may manifest with both superficial and deep features depending on the extent of its involvement in the dermal and subcutaneous layers. The pattern of involvement may be focal, segmental, or indeterminate.²⁴ In contrast, CH typically is a solitary vascular mass with prominent telangiectases, nodules, and radiating veins.⁶ Histologically, IH is composed of proliferative plump endothelial cells that form capillaries, and the lesion stains positively for GLUT-1, whereas CH does not.³⁰

Kaposiform hemangioendothelioma is classified as a locally aggressive vascular tumor that manifests either prenatally or in early infancy.³¹ It is described as a solitary, ill-defined, firm, purple plaque most commonly located on the extremities and retroperitoneum.^32-34 Histopathologically, these lesions are characterized by dilated lymphatic channels and irregular sheets or lobules of spindle-shaped endothelial cells infiltrating the dermis and subcutaneous fat.^33,35 In contrast to CH, KHE lesions show immunoreactivity to the markers podoplanin, lymphatic vessel endothelial receptor 1, and prospero homeobox 1 protein.^36,37 Notably, 70% of these tumors are complicated by the presence of Kasabach-Merritt phenomenon, a potentially life-threatening emergency that occurs when platelets are trapped within a vascular tumor, leading to the consumption of clotting factors, intralesional bleeding, and rapid enlargement of the tumor.³² The Kasabach-Merritt phenomenon manifests clinically as microangiopathic hemolytic anemia, severe thrombocytopenia, and disseminated intravascular coagulation. ³⁸ Although CH lesions also can be associated with thrombocytopenia and coagulopathy, they generally are mild and self-limited.¹⁸

Tufted angioma is a vascular tumor that arises within the first 5 years of life as firm violaceous papules or plaques, often with associated hyperhidrosis or hypertrichosis.^39,40 Although TA grows slowly for a period of time, it eventually stabilizes and persists, rarely regressing completely.⁴¹ These tumors share many similarities with KHE, and it has been suggested that they may be part of the same spectrum. 42 As with KHE, TA lesions show immunoreactivity to the markers podoplanin, lymphatic vessel endothelial receptor 1, and prospero homeobox 1 protein, which are negative in CH.^36,37 Although TA also can be complicated by Kasabach-Merritt phenomenon, the incidence is much lower (up to 38%).^43,44 As such, TAs tend to be recognized as more superficial benign lesions. However, they still can cause notable cosmetic and functional impairment and should be monitored closely, especially in the presence of associated symptoms or complications.

Arteriovenous malformation is a vascular lesion that results from errors during the embryonic development of vascular channels.⁴⁵ Although present at birth, it may not become clinically apparent until later in life. Arteriovenous malformations enlarge postnatally, and their growth is proportional to the developmental growth of the affected individual rather than the result of endothelial proliferation.⁴⁶ In infants, AVM may manifest as a faint vascular stain that can evolve over time into a pink patch associated with a palpable thrill during adolescence. ⁴ On Doppler flow imaging, AVMs are identified as fast-flow anomalies arising from an abnormal communication between high-pressure arterial systems and low-pressure venous systems without the presence of a capillary bed.⁴⁷ One of the differentiating factors between AVM and CH is that AVMs do not regress spontaneously and tend to have high recurrence rates, even with intervention. ⁴⁸ In contrast, CH can be categorized based on its postnatal involution pattern. Another distinguishing factor is that AVMs tend to be larger and more invasive than CHs.⁴⁶ Therefore, early diagnosis and intervention are crucial to prevent complications such as bleeding, seizures, or neurologic deficits associated with AVMs.¹

TOPLINE:

The tyrosine kinase 2 (TYK2) inhibitor TAK-279 demonstrated superiority to placebo in patients with active psoriatic arthritis (PsA), according to phase 2 trial results.

METHODOLOGY:

• Eligible patients were over 18 years old, had PsA for over 6 months, met the classification criteria for PsA, and had at least three swollen and tender joints despite prior nonsteroidal anti-inflammatory drug, disease-modifying antirheumatic drug, or biologic treatment.
• A total of 290 patients were randomized 1:1:1:1 to receive placebo, oral TAK-279 5 mg, 15 mg, or 30 mg once daily.
• The primary endpoint was a 20% improvement in the American College of Rheumatology response criteria (ACR20) at 12 weeks.

TAKEAWAY:

• More than half of patients assigned to TAK-279 15 mg (53.3%) and TAK-279 30 mg (54.2%) achieved ACR20 at 12 weeks, compared with 29.2% of those assigned to placebo.
• Psoriasis Area and Severity Index 75 response rates were also higher in patients assigned to TAK-279 30 mg (45.7%) or 15 mg (28.3%) than those in placebo (15.4%).
• Treatment-emergent adverse events (TEAEs) of any kind were numerically higher in the 30-mg group, though serious TEAEs were similar across all treatment arms.
• The most frequent adverse events were nasal pharyngitis, upper respiratory tract infections, headache, and rash, with rash being most common in the TAK-279 30-mg group.

IN PRACTICE:

“There are few targeted oral therapies for active PSA available currently,” said lead author Alan Kivitz, MD, Altoona Center for Clinical Research, Duncansville, Pennsylvania, “and [TAK-279], which was well tolerated and demonstrated superior efficacy versus placebo, may be a promising targeted oral therapy for patients with PsA.”
 

SOURCE:

Dr. Kivitz presented the study findings at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting, held in Vienna.

LIMITATIONS:

The study was a phase 2 trial, and larger studies in active PsA are needed (and currently being planned).
 

DISCLOSURES:

The phase 2 trial was funded by Nimbus and Takeda. Dr. Kivitz has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie, Amgen, Eli Lilly, GlaxoSmithKline, Pfizer, and UCB. He has stock or stock options in Pfizer, Amgen, GlaxoSmithKline, Gilead, Novartis, and Pfizer and has received consultant fees from Fresenius Kabi, Genzyme, Gilead, Grunenthal, GlaxoSmithKline, Horizon, Janssen, Pfizer, Selecta, SynAct Pharma, and Takeda. He has been part of a board or advisory board for ChemoCentryx, Horizon, Janssen, Novartis, Princeton Biopartners, and UCB. Other authors also disclosed many relationships with pharmaceutical companies.

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

TOPLINE:

The tyrosine kinase 2 (TYK2) inhibitor TAK-279 demonstrated superiority to placebo in patients with active psoriatic arthritis (PsA), according to phase 2 trial results.

METHODOLOGY:

• Eligible patients were over 18 years old, had PsA for over 6 months, met the classification criteria for PsA, and had at least three swollen and tender joints despite prior nonsteroidal anti-inflammatory drug, disease-modifying antirheumatic drug, or biologic treatment.
• A total of 290 patients were randomized 1:1:1:1 to receive placebo, oral TAK-279 5 mg, 15 mg, or 30 mg once daily.
• The primary endpoint was a 20% improvement in the American College of Rheumatology response criteria (ACR20) at 12 weeks.

TAKEAWAY:

• More than half of patients assigned to TAK-279 15 mg (53.3%) and TAK-279 30 mg (54.2%) achieved ACR20 at 12 weeks, compared with 29.2% of those assigned to placebo.
• Psoriasis Area and Severity Index 75 response rates were also higher in patients assigned to TAK-279 30 mg (45.7%) or 15 mg (28.3%) than those in placebo (15.4%).
• Treatment-emergent adverse events (TEAEs) of any kind were numerically higher in the 30-mg group, though serious TEAEs were similar across all treatment arms.
• The most frequent adverse events were nasal pharyngitis, upper respiratory tract infections, headache, and rash, with rash being most common in the TAK-279 30-mg group.

IN PRACTICE:

“There are few targeted oral therapies for active PSA available currently,” said lead author Alan Kivitz, MD, Altoona Center for Clinical Research, Duncansville, Pennsylvania, “and [TAK-279], which was well tolerated and demonstrated superior efficacy versus placebo, may be a promising targeted oral therapy for patients with PsA.”
 

SOURCE:

Dr. Kivitz presented the study findings at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting, held in Vienna.

LIMITATIONS:

The study was a phase 2 trial, and larger studies in active PsA are needed (and currently being planned).
 

DISCLOSURES:

The phase 2 trial was funded by Nimbus and Takeda. Dr. Kivitz has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie, Amgen, Eli Lilly, GlaxoSmithKline, Pfizer, and UCB. He has stock or stock options in Pfizer, Amgen, GlaxoSmithKline, Gilead, Novartis, and Pfizer and has received consultant fees from Fresenius Kabi, Genzyme, Gilead, Grunenthal, GlaxoSmithKline, Horizon, Janssen, Pfizer, Selecta, SynAct Pharma, and Takeda. He has been part of a board or advisory board for ChemoCentryx, Horizon, Janssen, Novartis, Princeton Biopartners, and UCB. Other authors also disclosed many relationships with pharmaceutical companies.

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

TOPLINE:

The tyrosine kinase 2 (TYK2) inhibitor TAK-279 demonstrated superiority to placebo in patients with active psoriatic arthritis (PsA), according to phase 2 trial results.

METHODOLOGY:

• Eligible patients were over 18 years old, had PsA for over 6 months, met the classification criteria for PsA, and had at least three swollen and tender joints despite prior nonsteroidal anti-inflammatory drug, disease-modifying antirheumatic drug, or biologic treatment.
• A total of 290 patients were randomized 1:1:1:1 to receive placebo, oral TAK-279 5 mg, 15 mg, or 30 mg once daily.
• The primary endpoint was a 20% improvement in the American College of Rheumatology response criteria (ACR20) at 12 weeks.

TAKEAWAY:

• More than half of patients assigned to TAK-279 15 mg (53.3%) and TAK-279 30 mg (54.2%) achieved ACR20 at 12 weeks, compared with 29.2% of those assigned to placebo.
• Psoriasis Area and Severity Index 75 response rates were also higher in patients assigned to TAK-279 30 mg (45.7%) or 15 mg (28.3%) than those in placebo (15.4%).
• Treatment-emergent adverse events (TEAEs) of any kind were numerically higher in the 30-mg group, though serious TEAEs were similar across all treatment arms.
• The most frequent adverse events were nasal pharyngitis, upper respiratory tract infections, headache, and rash, with rash being most common in the TAK-279 30-mg group.

IN PRACTICE:

“There are few targeted oral therapies for active PSA available currently,” said lead author Alan Kivitz, MD, Altoona Center for Clinical Research, Duncansville, Pennsylvania, “and [TAK-279], which was well tolerated and demonstrated superior efficacy versus placebo, may be a promising targeted oral therapy for patients with PsA.”
 

SOURCE:

Dr. Kivitz presented the study findings at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting, held in Vienna.

LIMITATIONS:

The study was a phase 2 trial, and larger studies in active PsA are needed (and currently being planned).
 

DISCLOSURES:

The phase 2 trial was funded by Nimbus and Takeda. Dr. Kivitz has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie, Amgen, Eli Lilly, GlaxoSmithKline, Pfizer, and UCB. He has stock or stock options in Pfizer, Amgen, GlaxoSmithKline, Gilead, Novartis, and Pfizer and has received consultant fees from Fresenius Kabi, Genzyme, Gilead, Grunenthal, GlaxoSmithKline, Horizon, Janssen, Pfizer, Selecta, SynAct Pharma, and Takeda. He has been part of a board or advisory board for ChemoCentryx, Horizon, Janssen, Novartis, Princeton Biopartners, and UCB. Other authors also disclosed many relationships with pharmaceutical companies.

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

TOPLINE:

Treatment of patients with active psoriatic arthritis with sonelokimab — an interleukin (IL)-17A- and IL-17F-inhibiting nanobody — led to a higher percentage of patients with 50% or greater improvement in American College of Rheumatology response criteria (ACR50) compared with the placebo in a phase 2 trial.

METHODOLOGY:

• Sonelokimab is a 40-kDa nanobody that binds to IL-17A, IL-17F, and albumin.
• Eligible patients were at least 18 years old with active PsA (at least three swollen and three tender joints) and had a psoriasis diagnosis.
• A total of 207 patients were randomized 1:1:1:1 to every 4 weeks receive placebo, sonelokimab 60 mg with no induction (NI) period, sonelokimab 60 mg with induction, and sonelokimab 120 mg with induction.
• Induction was once every 2 weeks up to week 8 of the trial.
• The primary endpoint was meeting ACR20 response criteria at 12 weeks.

TAKEAWAY:

• About 46% of patients in the sonelokimab 120-mg and 60-mg groups achieved ACR50, compared with 36.6% in the sonelokimab 60-mg NI group and 20% of those assigned to placebo.
• ACR20 and 90% or greater reduction in Psoriasis Area and Severity Index score response rates were higher in all three sonelokimab groups than in the placebo group.
• There were no unexpected safety findings during the trial, and no cases of inflammatory bowel disease or major cardiovascular events.
• There were two cases of oral candidiasis, which did not lead to study discontinuation.

IN PRACTICE:

These data “support further exploration in phase 3 trials of sonelokimab to evaluate its potential for the treatment of PsA,” the authors noted in the presentation.

SOURCE:

Iain B. McInnes, MD, PhD, of the University of Glasgow, Glasgow, Scotland, presented these phase 2 trial results at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Congress, held in Vienna.

LIMITATIONS:

The results are from a phase 2 trial, and more research is needed.

DISCLOSURES:

MoonLake Immunotherapeutics funded the research. Dr. McInnes disclosed relationships with AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Causeway Therapeutics, Cabaletta Bio, Compugen, Evelo, Gilead, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, MoonLake Immunotherapeutics, Pfizer, Sanofi Regeneron, and UCB. Other authors also disclosed many relationships with pharmaceutical companies.

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

TOPLINE:

Treatment of patients with active psoriatic arthritis with sonelokimab — an interleukin (IL)-17A- and IL-17F-inhibiting nanobody — led to a higher percentage of patients with 50% or greater improvement in American College of Rheumatology response criteria (ACR50) compared with the placebo in a phase 2 trial.

METHODOLOGY:

• Sonelokimab is a 40-kDa nanobody that binds to IL-17A, IL-17F, and albumin.
• Eligible patients were at least 18 years old with active PsA (at least three swollen and three tender joints) and had a psoriasis diagnosis.
• A total of 207 patients were randomized 1:1:1:1 to every 4 weeks receive placebo, sonelokimab 60 mg with no induction (NI) period, sonelokimab 60 mg with induction, and sonelokimab 120 mg with induction.
• Induction was once every 2 weeks up to week 8 of the trial.
• The primary endpoint was meeting ACR20 response criteria at 12 weeks.

TAKEAWAY:

• About 46% of patients in the sonelokimab 120-mg and 60-mg groups achieved ACR50, compared with 36.6% in the sonelokimab 60-mg NI group and 20% of those assigned to placebo.
• ACR20 and 90% or greater reduction in Psoriasis Area and Severity Index score response rates were higher in all three sonelokimab groups than in the placebo group.
• There were no unexpected safety findings during the trial, and no cases of inflammatory bowel disease or major cardiovascular events.
• There were two cases of oral candidiasis, which did not lead to study discontinuation.

IN PRACTICE:

These data “support further exploration in phase 3 trials of sonelokimab to evaluate its potential for the treatment of PsA,” the authors noted in the presentation.

SOURCE:

Iain B. McInnes, MD, PhD, of the University of Glasgow, Glasgow, Scotland, presented these phase 2 trial results at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Congress, held in Vienna.

LIMITATIONS:

The results are from a phase 2 trial, and more research is needed.

DISCLOSURES:

MoonLake Immunotherapeutics funded the research. Dr. McInnes disclosed relationships with AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Causeway Therapeutics, Cabaletta Bio, Compugen, Evelo, Gilead, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, MoonLake Immunotherapeutics, Pfizer, Sanofi Regeneron, and UCB. Other authors also disclosed many relationships with pharmaceutical companies.

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

TOPLINE:

Treatment of patients with active psoriatic arthritis with sonelokimab — an interleukin (IL)-17A- and IL-17F-inhibiting nanobody — led to a higher percentage of patients with 50% or greater improvement in American College of Rheumatology response criteria (ACR50) compared with the placebo in a phase 2 trial.

METHODOLOGY:

• Sonelokimab is a 40-kDa nanobody that binds to IL-17A, IL-17F, and albumin.
• Eligible patients were at least 18 years old with active PsA (at least three swollen and three tender joints) and had a psoriasis diagnosis.
• A total of 207 patients were randomized 1:1:1:1 to every 4 weeks receive placebo, sonelokimab 60 mg with no induction (NI) period, sonelokimab 60 mg with induction, and sonelokimab 120 mg with induction.
• Induction was once every 2 weeks up to week 8 of the trial.
• The primary endpoint was meeting ACR20 response criteria at 12 weeks.

TAKEAWAY:

• About 46% of patients in the sonelokimab 120-mg and 60-mg groups achieved ACR50, compared with 36.6% in the sonelokimab 60-mg NI group and 20% of those assigned to placebo.
• ACR20 and 90% or greater reduction in Psoriasis Area and Severity Index score response rates were higher in all three sonelokimab groups than in the placebo group.
• There were no unexpected safety findings during the trial, and no cases of inflammatory bowel disease or major cardiovascular events.
• There were two cases of oral candidiasis, which did not lead to study discontinuation.

IN PRACTICE:

These data “support further exploration in phase 3 trials of sonelokimab to evaluate its potential for the treatment of PsA,” the authors noted in the presentation.

SOURCE:

Iain B. McInnes, MD, PhD, of the University of Glasgow, Glasgow, Scotland, presented these phase 2 trial results at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Congress, held in Vienna.

LIMITATIONS:

The results are from a phase 2 trial, and more research is needed.

DISCLOSURES:

MoonLake Immunotherapeutics funded the research. Dr. McInnes disclosed relationships with AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Causeway Therapeutics, Cabaletta Bio, Compugen, Evelo, Gilead, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, MoonLake Immunotherapeutics, Pfizer, Sanofi Regeneron, and UCB. Other authors also disclosed many relationships with pharmaceutical companies.

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

The Food and Drug Administration (FDA) has issued new draft guidance that does not require additional switching studies for biosimilars seeking interchangeability. These studies were previously recommended to demonstrate that switching between the biosimilar and its reference product showed no greater risk than using the reference product alone.

“The recommendations in today’s draft guidance, when finalized, will provide clarity and transparency about the FDA’s thinking and align the review and approval process with existing and emerging science,” said Sarah Yim, MD, director of the FDA’s Office of Therapeutic Biologics and Biosimilars in a statement on June 20. “We have gained valuable experience reviewing both biosimilar and interchangeable biosimilar medications over the past 10 years. Both biosimilars and interchangeable biosimilars meet the same high standard of biosimilarity for FDA approval and both are as safe and effective as the reference product.”

An interchangeable status allows a biosimilar product to be swapped with the reference product without involvement from the prescribing provider, depending on state law.

While switching studies were not required under previous FDA guidance, the 2019 document did state that the agency “expects that applications generally will include data from a switching study or studies in one or more appropriate conditions of use.”

However, of the 13 biosimilars that received interchangeability status, 9 did not include switching study data.

“Experience has shown that, for the products approved as biosimilars to date, the risk in terms of safety or diminished efficacy is insignificant following single or multiple switches between a reference product and a biosimilar product,” the FDA stated. The agency’s investigators also conducted a systematic review of switching studies, which found no differences in risk for death, serious adverse events, and treatment discontinuations in participants switched between biosimilars and reference products and those that remained on reference products.

“Additionally, today’s analytical tools can accurately evaluate the structure and effects [of] biologic products, both in the lab (in vitro) and in living organisms (in vivo) with more precision and sensitivity than switching studies,” the agency noted.

The FDA is now calling for commentary on these draft recommendations to be submitted by Aug. 20, 2024.

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

The Food and Drug Administration (FDA) has issued new draft guidance that does not require additional switching studies for biosimilars seeking interchangeability. These studies were previously recommended to demonstrate that switching between the biosimilar and its reference product showed no greater risk than using the reference product alone.

“The recommendations in today’s draft guidance, when finalized, will provide clarity and transparency about the FDA’s thinking and align the review and approval process with existing and emerging science,” said Sarah Yim, MD, director of the FDA’s Office of Therapeutic Biologics and Biosimilars in a statement on June 20. “We have gained valuable experience reviewing both biosimilar and interchangeable biosimilar medications over the past 10 years. Both biosimilars and interchangeable biosimilars meet the same high standard of biosimilarity for FDA approval and both are as safe and effective as the reference product.”

An interchangeable status allows a biosimilar product to be swapped with the reference product without involvement from the prescribing provider, depending on state law.

While switching studies were not required under previous FDA guidance, the 2019 document did state that the agency “expects that applications generally will include data from a switching study or studies in one or more appropriate conditions of use.”

However, of the 13 biosimilars that received interchangeability status, 9 did not include switching study data.

“Experience has shown that, for the products approved as biosimilars to date, the risk in terms of safety or diminished efficacy is insignificant following single or multiple switches between a reference product and a biosimilar product,” the FDA stated. The agency’s investigators also conducted a systematic review of switching studies, which found no differences in risk for death, serious adverse events, and treatment discontinuations in participants switched between biosimilars and reference products and those that remained on reference products.

“Additionally, today’s analytical tools can accurately evaluate the structure and effects [of] biologic products, both in the lab (in vitro) and in living organisms (in vivo) with more precision and sensitivity than switching studies,” the agency noted.

The FDA is now calling for commentary on these draft recommendations to be submitted by Aug. 20, 2024.

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

The Food and Drug Administration (FDA) has issued new draft guidance that does not require additional switching studies for biosimilars seeking interchangeability. These studies were previously recommended to demonstrate that switching between the biosimilar and its reference product showed no greater risk than using the reference product alone.

“The recommendations in today’s draft guidance, when finalized, will provide clarity and transparency about the FDA’s thinking and align the review and approval process with existing and emerging science,” said Sarah Yim, MD, director of the FDA’s Office of Therapeutic Biologics and Biosimilars in a statement on June 20. “We have gained valuable experience reviewing both biosimilar and interchangeable biosimilar medications over the past 10 years. Both biosimilars and interchangeable biosimilars meet the same high standard of biosimilarity for FDA approval and both are as safe and effective as the reference product.”

An interchangeable status allows a biosimilar product to be swapped with the reference product without involvement from the prescribing provider, depending on state law.

While switching studies were not required under previous FDA guidance, the 2019 document did state that the agency “expects that applications generally will include data from a switching study or studies in one or more appropriate conditions of use.”

However, of the 13 biosimilars that received interchangeability status, 9 did not include switching study data.

“Experience has shown that, for the products approved as biosimilars to date, the risk in terms of safety or diminished efficacy is insignificant following single or multiple switches between a reference product and a biosimilar product,” the FDA stated. The agency’s investigators also conducted a systematic review of switching studies, which found no differences in risk for death, serious adverse events, and treatment discontinuations in participants switched between biosimilars and reference products and those that remained on reference products.

“Additionally, today’s analytical tools can accurately evaluate the structure and effects [of] biologic products, both in the lab (in vitro) and in living organisms (in vivo) with more precision and sensitivity than switching studies,” the agency noted.

The FDA is now calling for commentary on these draft recommendations to be submitted by Aug. 20, 2024.

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

In this real-life study, Patruno and colleagues found that dupilumab worked well but more slowly in patients with a higher body mass index (BMI). On the basis of these findings, if patients are not in a hurry, the standard dose of dupilumab should eventually work, regardless of BMI. If patients are in a hurry to see improvement, perhaps dose escalation could be considered for patients with a high BMI, or perhaps topical triamcinolone could be used to speed time-to–initial resolution in the high-BMI population.

In the very well-done study by Silverberg and colleagues, tapinarof was effective, well tolerated, and generally safe for atopic dermatitis in adults and children. Great! Topical tapinarof should soon be another good option for our patients with atopic dermatitis. How valuable will it be? We already have topical corticosteroids that are very effective for atopic dermatitis, and we have multiple other nonsteroidal topical agents, including topical calcineurin inhibitors and topical ruxolitinib. 

Perhaps the biggest limitation of all these treatments is poor adherence to topical treatment. I'm not sure how effective even highly effective nonsteroidal topicals will be for patients who did not respond to topical steroids when the primary reason for topical steroid failure is poor treatment adherence. I'd love to see the development of a once-a-week or once-a-month topical therapy that would address the poor-adherence hurdle.

Abrocitinib is an effective treatment for improving atopic dermatitis. Although atopic dermatitis is a chronic condition requiring long-term management, we'd like to minimize exposure to the drug to avoid side effects. Thyssen and colleagues described the effectiveness of two maintenance treatment regimens: continuing 200 mg/d or reducing the dose to 100 mg/d. Both regimens prevented flares more than did placebo. This study also provided information on safety of the maintenance regimens. Rates of herpetic infections were low across all the groups, but unlike the two treatment groups, there were no cases of herpes simplex infection in the patients in the placebo arm.
 

In this real-life study, Patruno and colleagues found that dupilumab worked well but more slowly in patients with a higher body mass index (BMI). On the basis of these findings, if patients are not in a hurry, the standard dose of dupilumab should eventually work, regardless of BMI. If patients are in a hurry to see improvement, perhaps dose escalation could be considered for patients with a high BMI, or perhaps topical triamcinolone could be used to speed time-to–initial resolution in the high-BMI population.

In the very well-done study by Silverberg and colleagues, tapinarof was effective, well tolerated, and generally safe for atopic dermatitis in adults and children. Great! Topical tapinarof should soon be another good option for our patients with atopic dermatitis. How valuable will it be? We already have topical corticosteroids that are very effective for atopic dermatitis, and we have multiple other nonsteroidal topical agents, including topical calcineurin inhibitors and topical ruxolitinib. 

Perhaps the biggest limitation of all these treatments is poor adherence to topical treatment. I'm not sure how effective even highly effective nonsteroidal topicals will be for patients who did not respond to topical steroids when the primary reason for topical steroid failure is poor treatment adherence. I'd love to see the development of a once-a-week or once-a-month topical therapy that would address the poor-adherence hurdle.

Abrocitinib is an effective treatment for improving atopic dermatitis. Although atopic dermatitis is a chronic condition requiring long-term management, we'd like to minimize exposure to the drug to avoid side effects. Thyssen and colleagues described the effectiveness of two maintenance treatment regimens: continuing 200 mg/d or reducing the dose to 100 mg/d. Both regimens prevented flares more than did placebo. This study also provided information on safety of the maintenance regimens. Rates of herpetic infections were low across all the groups, but unlike the two treatment groups, there were no cases of herpes simplex infection in the patients in the placebo arm.
 

In this real-life study, Patruno and colleagues found that dupilumab worked well but more slowly in patients with a higher body mass index (BMI). On the basis of these findings, if patients are not in a hurry, the standard dose of dupilumab should eventually work, regardless of BMI. If patients are in a hurry to see improvement, perhaps dose escalation could be considered for patients with a high BMI, or perhaps topical triamcinolone could be used to speed time-to–initial resolution in the high-BMI population.

In the very well-done study by Silverberg and colleagues, tapinarof was effective, well tolerated, and generally safe for atopic dermatitis in adults and children. Great! Topical tapinarof should soon be another good option for our patients with atopic dermatitis. How valuable will it be? We already have topical corticosteroids that are very effective for atopic dermatitis, and we have multiple other nonsteroidal topical agents, including topical calcineurin inhibitors and topical ruxolitinib. 

Perhaps the biggest limitation of all these treatments is poor adherence to topical treatment. I'm not sure how effective even highly effective nonsteroidal topicals will be for patients who did not respond to topical steroids when the primary reason for topical steroid failure is poor treatment adherence. I'd love to see the development of a once-a-week or once-a-month topical therapy that would address the poor-adherence hurdle.

Abrocitinib is an effective treatment for improving atopic dermatitis. Although atopic dermatitis is a chronic condition requiring long-term management, we'd like to minimize exposure to the drug to avoid side effects. Thyssen and colleagues described the effectiveness of two maintenance treatment regimens: continuing 200 mg/d or reducing the dose to 100 mg/d. Both regimens prevented flares more than did placebo. This study also provided information on safety of the maintenance regimens. Rates of herpetic infections were low across all the groups, but unlike the two treatment groups, there were no cases of herpes simplex infection in the patients in the placebo arm.
 

Federal health officials with the US Centers for Disease Control and Prevention (CDC) have issued an alert, warning health professionals and the public about an increased risk for dengue virus infections in the United States.

The global incidence of dengue in 2024 is the highest on record, reported the agency.

In the Americas, more than 9.7 million cases of dengue have been reported in the first 6 months of 2024 — more than double the 4.6 million cases reported in all of 2023.

In the United States, Puerto Rico has declared a public health emergency, with 1498 dengue cases reported so far and a “higher-than-expected” number of dengue cases having been identified among US travelers in the first half of this year at 745 cases, according to the alert.

The CDC reports 197 dengue cases in Florida, 134 in New York, 50 in Massachusetts, 40 in California, 14 in Colorado, nine in Arizona, and eight in the District of Columbia, among others.

Transmitted by infected Aedes genus mosquitoes, dengue is the most common arboviral disease globally and is a nationally notifiable disease in the United States.

The six US territories and freely associated states with frequent or continuous dengue transmission are Puerto Rico, American Samoa, the US Virgin Islands, the Federated States of Micronesia, the Republic of the Marshall Islands, and the Republic of Palau.
 

Monitoring for Dengue

With rising global and domestic cases of dengue, the CDC urges healthcare providers to monitor for dengue:

• Maintain a high index of suspicion in patients with fever who have been in areas with frequent or continuous dengue transmission within 14 days before illness onset.
• Order diagnostic tests for acute dengue infection such as reverse transcription polymerase chain reaction and immunoglobulin M (IgM) antibody tests or nonstructural protein 1 antigen tests and IgM antibody tests.
• Ensure timely reporting of dengue cases to public health authorities.
• Promote mosquito bite prevention measures among people living in or visiting areas with frequent or continuous dengue transmission.

Roughly one in four dengue virus infections are symptomatic and can be mild or severe. Symptoms begin after an incubation period of about 5-7 days.

Symptoms include fever accompanied by nonspecific signs and symptoms such as nausea, vomiting, rash, muscle aches, joint pain, bone pain, pain behind the eyes, headache, or low white blood cell counts.
 

Disease Progression

Warning signs that may predict progression to severe disease include abdominal pain or tenderness, persistent vomiting, clinical fluid accumulation, mucosal bleeding, lethargy or restlessness, and progressive increase in hematocrit or liver enlargement.

One in 20 people with symptomatic dengue will develop severe disease, with bleeding, shock, or respiratory distress caused by plasma leakage or end-organ impairment.

Infants aged a year or younger, pregnant people, adults aged 65 years or older, people with certain medical conditions, and those with previous dengue infections are at increased risk for severe dengue.

“Healthcare providers should be prepared to recognize, diagnose, manage, and report dengue cases to health authorities; public health partners should investigate cases and disseminate clear prevention messages to the public,” the alert stated.

The CDC is actively implementing several strategies to address the increase in cases of dengue in the United States. In early April, the agency launched a program-led emergency response and is providing monthly situational updates on dengue to partners, stakeholders, and jurisdictions.

The CDC is also expanding laboratory capacity to improve laboratory testing approaches; collaborating with state, tribal, local, and territorial health departments to strengthen dengue surveillance and recommend prevention strategies; and working to educate the public on dengue prevention.

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

Federal health officials with the US Centers for Disease Control and Prevention (CDC) have issued an alert, warning health professionals and the public about an increased risk for dengue virus infections in the United States.

The global incidence of dengue in 2024 is the highest on record, reported the agency.

In the Americas, more than 9.7 million cases of dengue have been reported in the first 6 months of 2024 — more than double the 4.6 million cases reported in all of 2023.

In the United States, Puerto Rico has declared a public health emergency, with 1498 dengue cases reported so far and a “higher-than-expected” number of dengue cases having been identified among US travelers in the first half of this year at 745 cases, according to the alert.

The CDC reports 197 dengue cases in Florida, 134 in New York, 50 in Massachusetts, 40 in California, 14 in Colorado, nine in Arizona, and eight in the District of Columbia, among others.

Transmitted by infected Aedes genus mosquitoes, dengue is the most common arboviral disease globally and is a nationally notifiable disease in the United States.

The six US territories and freely associated states with frequent or continuous dengue transmission are Puerto Rico, American Samoa, the US Virgin Islands, the Federated States of Micronesia, the Republic of the Marshall Islands, and the Republic of Palau.
 

Monitoring for Dengue

With rising global and domestic cases of dengue, the CDC urges healthcare providers to monitor for dengue:

• Maintain a high index of suspicion in patients with fever who have been in areas with frequent or continuous dengue transmission within 14 days before illness onset.
• Order diagnostic tests for acute dengue infection such as reverse transcription polymerase chain reaction and immunoglobulin M (IgM) antibody tests or nonstructural protein 1 antigen tests and IgM antibody tests.
• Ensure timely reporting of dengue cases to public health authorities.
• Promote mosquito bite prevention measures among people living in or visiting areas with frequent or continuous dengue transmission.

Roughly one in four dengue virus infections are symptomatic and can be mild or severe. Symptoms begin after an incubation period of about 5-7 days.

Symptoms include fever accompanied by nonspecific signs and symptoms such as nausea, vomiting, rash, muscle aches, joint pain, bone pain, pain behind the eyes, headache, or low white blood cell counts.
 

Disease Progression

Warning signs that may predict progression to severe disease include abdominal pain or tenderness, persistent vomiting, clinical fluid accumulation, mucosal bleeding, lethargy or restlessness, and progressive increase in hematocrit or liver enlargement.

One in 20 people with symptomatic dengue will develop severe disease, with bleeding, shock, or respiratory distress caused by plasma leakage or end-organ impairment.

Infants aged a year or younger, pregnant people, adults aged 65 years or older, people with certain medical conditions, and those with previous dengue infections are at increased risk for severe dengue.

“Healthcare providers should be prepared to recognize, diagnose, manage, and report dengue cases to health authorities; public health partners should investigate cases and disseminate clear prevention messages to the public,” the alert stated.

The CDC is actively implementing several strategies to address the increase in cases of dengue in the United States. In early April, the agency launched a program-led emergency response and is providing monthly situational updates on dengue to partners, stakeholders, and jurisdictions.

The CDC is also expanding laboratory capacity to improve laboratory testing approaches; collaborating with state, tribal, local, and territorial health departments to strengthen dengue surveillance and recommend prevention strategies; and working to educate the public on dengue prevention.

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

Federal health officials with the US Centers for Disease Control and Prevention (CDC) have issued an alert, warning health professionals and the public about an increased risk for dengue virus infections in the United States.

The global incidence of dengue in 2024 is the highest on record, reported the agency.

In the Americas, more than 9.7 million cases of dengue have been reported in the first 6 months of 2024 — more than double the 4.6 million cases reported in all of 2023.

In the United States, Puerto Rico has declared a public health emergency, with 1498 dengue cases reported so far and a “higher-than-expected” number of dengue cases having been identified among US travelers in the first half of this year at 745 cases, according to the alert.

The CDC reports 197 dengue cases in Florida, 134 in New York, 50 in Massachusetts, 40 in California, 14 in Colorado, nine in Arizona, and eight in the District of Columbia, among others.

Transmitted by infected Aedes genus mosquitoes, dengue is the most common arboviral disease globally and is a nationally notifiable disease in the United States.

The six US territories and freely associated states with frequent or continuous dengue transmission are Puerto Rico, American Samoa, the US Virgin Islands, the Federated States of Micronesia, the Republic of the Marshall Islands, and the Republic of Palau.
 

Monitoring for Dengue

With rising global and domestic cases of dengue, the CDC urges healthcare providers to monitor for dengue:

• Maintain a high index of suspicion in patients with fever who have been in areas with frequent or continuous dengue transmission within 14 days before illness onset.
• Order diagnostic tests for acute dengue infection such as reverse transcription polymerase chain reaction and immunoglobulin M (IgM) antibody tests or nonstructural protein 1 antigen tests and IgM antibody tests.
• Ensure timely reporting of dengue cases to public health authorities.
• Promote mosquito bite prevention measures among people living in or visiting areas with frequent or continuous dengue transmission.

Roughly one in four dengue virus infections are symptomatic and can be mild or severe. Symptoms begin after an incubation period of about 5-7 days.

Symptoms include fever accompanied by nonspecific signs and symptoms such as nausea, vomiting, rash, muscle aches, joint pain, bone pain, pain behind the eyes, headache, or low white blood cell counts.
 

Disease Progression

Warning signs that may predict progression to severe disease include abdominal pain or tenderness, persistent vomiting, clinical fluid accumulation, mucosal bleeding, lethargy or restlessness, and progressive increase in hematocrit or liver enlargement.

One in 20 people with symptomatic dengue will develop severe disease, with bleeding, shock, or respiratory distress caused by plasma leakage or end-organ impairment.

Infants aged a year or younger, pregnant people, adults aged 65 years or older, people with certain medical conditions, and those with previous dengue infections are at increased risk for severe dengue.

“Healthcare providers should be prepared to recognize, diagnose, manage, and report dengue cases to health authorities; public health partners should investigate cases and disseminate clear prevention messages to the public,” the alert stated.

The CDC is actively implementing several strategies to address the increase in cases of dengue in the United States. In early April, the agency launched a program-led emergency response and is providing monthly situational updates on dengue to partners, stakeholders, and jurisdictions.

The CDC is also expanding laboratory capacity to improve laboratory testing approaches; collaborating with state, tribal, local, and territorial health departments to strengthen dengue surveillance and recommend prevention strategies; and working to educate the public on dengue prevention.

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

Key clinical point: Patients with atopic dermatitis (AD) who had many or severe flares were more likely to report higher disease severity and impairment in quality of life than those who had no or few flares.

Major finding: Patients with 1-5, 6-10, or >10 flares had higher median Patient-Oriented SCORing for Atopic Dermatitis (29.7, 36.3, and 42.9, respectively) and Dermatology Life Quality Index (3, 4, and 7, respectively) scores than those without flares.

Study details: This Danish population-based study included 1557 patients with AD who had 0 (n = 57), 1-5 (n = 698), 6-10 (n = 324), or >10 (n = 478) flares during the past 12 months.

Disclosures: The study was funded by Almirall S.A., Barcelona, Spain. Three authors declared being employees of Almirall, whereas the remaining authors reported having various ties with Almirall and other sources.

Source: Nielsen M-L, Nymand LK, Domenech Pena A, et al. Characterization of patients with atopic dermatitis based on flare patterns and severity of disease: A Danish population-based study. J Eur Acad Dermatol Venereol. 2024 (May 30). doi: 10.1111/jdv.20160 Source

Key clinical point: Patients with atopic dermatitis (AD) who had many or severe flares were more likely to report higher disease severity and impairment in quality of life than those who had no or few flares.

Major finding: Patients with 1-5, 6-10, or >10 flares had higher median Patient-Oriented SCORing for Atopic Dermatitis (29.7, 36.3, and 42.9, respectively) and Dermatology Life Quality Index (3, 4, and 7, respectively) scores than those without flares.

Study details: This Danish population-based study included 1557 patients with AD who had 0 (n = 57), 1-5 (n = 698), 6-10 (n = 324), or >10 (n = 478) flares during the past 12 months.

Disclosures: The study was funded by Almirall S.A., Barcelona, Spain. Three authors declared being employees of Almirall, whereas the remaining authors reported having various ties with Almirall and other sources.

Source: Nielsen M-L, Nymand LK, Domenech Pena A, et al. Characterization of patients with atopic dermatitis based on flare patterns and severity of disease: A Danish population-based study. J Eur Acad Dermatol Venereol. 2024 (May 30). doi: 10.1111/jdv.20160 Source

Key clinical point: Patients with atopic dermatitis (AD) who had many or severe flares were more likely to report higher disease severity and impairment in quality of life than those who had no or few flares.

Major finding: Patients with 1-5, 6-10, or >10 flares had higher median Patient-Oriented SCORing for Atopic Dermatitis (29.7, 36.3, and 42.9, respectively) and Dermatology Life Quality Index (3, 4, and 7, respectively) scores than those without flares.

Study details: This Danish population-based study included 1557 patients with AD who had 0 (n = 57), 1-5 (n = 698), 6-10 (n = 324), or >10 (n = 478) flares during the past 12 months.

Disclosures: The study was funded by Almirall S.A., Barcelona, Spain. Three authors declared being employees of Almirall, whereas the remaining authors reported having various ties with Almirall and other sources.

Source: Nielsen M-L, Nymand LK, Domenech Pena A, et al. Characterization of patients with atopic dermatitis based on flare patterns and severity of disease: A Danish population-based study. J Eur Acad Dermatol Venereol. 2024 (May 30). doi: 10.1111/jdv.20160 Source

Key clinical point: Patients with atopic dermatitis (AD) who had many or severe flares were more likely to report higher disease severity and impairment in quality of life than those who had no or few flares.

Major finding: Patients with 1-5, 6-10, or >10 flares had higher median Patient-Oriented SCORing for Atopic Dermatitis (29.7, 36.3, and 42.9, respectively) and Dermatology Life Quality Index (3, 4, and 7, respectively) scores than those without flares.

Study details: This Danish population-based study included 1557 patients with AD who had 0 (n = 57), 1-5 (n = 698), 6-10 (n = 324), or >10 (n = 478) flares during the past 12 months.

Disclosures: The study was funded by Almirall S.A., Barcelona, Spain. Three authors declared being employees of Almirall, whereas the remaining authors reported having various ties with Almirall and other sources.

Source: Nielsen M-L, Nymand LK, Domenech Pena A, et al. Characterization of patients with atopic dermatitis based on flare patterns and severity of disease: A Danish population-based study. J Eur Acad Dermatol Venereol. 2024 (May 30). doi: 10.1111/jdv.20160 Source

Key clinical point: Patients with atopic dermatitis (AD) who had many or severe flares were more likely to report higher disease severity and impairment in quality of life than those who had no or few flares.

Major finding: Patients with 1-5, 6-10, or >10 flares had higher median Patient-Oriented SCORing for Atopic Dermatitis (29.7, 36.3, and 42.9, respectively) and Dermatology Life Quality Index (3, 4, and 7, respectively) scores than those without flares.

Study details: This Danish population-based study included 1557 patients with AD who had 0 (n = 57), 1-5 (n = 698), 6-10 (n = 324), or >10 (n = 478) flares during the past 12 months.

Disclosures: The study was funded by Almirall S.A., Barcelona, Spain. Three authors declared being employees of Almirall, whereas the remaining authors reported having various ties with Almirall and other sources.

Source: Nielsen M-L, Nymand LK, Domenech Pena A, et al. Characterization of patients with atopic dermatitis based on flare patterns and severity of disease: A Danish population-based study. J Eur Acad Dermatol Venereol. 2024 (May 30). doi: 10.1111/jdv.20160 Source

Key clinical point: Patients with atopic dermatitis (AD) who had many or severe flares were more likely to report higher disease severity and impairment in quality of life than those who had no or few flares.

Major finding: Patients with 1-5, 6-10, or >10 flares had higher median Patient-Oriented SCORing for Atopic Dermatitis (29.7, 36.3, and 42.9, respectively) and Dermatology Life Quality Index (3, 4, and 7, respectively) scores than those without flares.

Study details: This Danish population-based study included 1557 patients with AD who had 0 (n = 57), 1-5 (n = 698), 6-10 (n = 324), or >10 (n = 478) flares during the past 12 months.

Disclosures: The study was funded by Almirall S.A., Barcelona, Spain. Three authors declared being employees of Almirall, whereas the remaining authors reported having various ties with Almirall and other sources.

Source: Nielsen M-L, Nymand LK, Domenech Pena A, et al. Characterization of patients with atopic dermatitis based on flare patterns and severity of disease: A Danish population-based study. J Eur Acad Dermatol Venereol. 2024 (May 30). doi: 10.1111/jdv.20160 Source

Key clinical point: Patients with polycystic ovary syndrome (PCOS) had a significantly increased risk for atopic dermatitis (AD), and patients with AD had a significantly increased risk for PCOS.

Major finding: The risk of developing AD was significantly higher in patients with PCOS (adjusted odds ratio [aOR] 1.99; P < .001) than in control participants. Similarly, the risk of developing PCOS was significantly higher in patients with AD (aOR 1.86; P < .001) than in control participants.

Study details: This nested case-control study included 3234 participants with PCOS who were matched with 12,936 control participants without PCOS using nearest-neighbor propensity-score matching, of whom 293 (4.55%) with PCOS and 588 (9.06%) without PCOS had AD.

Disclosures: This study did not disclose any source of funding. The authors declared no conflicts of interest.

Source: Kim IH, Andrade LF, Haq Z, et al. Association of polycystic ovary syndrome with atopic dermatitis: A case control study. Arch Dermatol Res. 2024;316:258. doi: 10.1007/s00403-024-03102-0 Source

Key clinical point: Patients with polycystic ovary syndrome (PCOS) had a significantly increased risk for atopic dermatitis (AD), and patients with AD had a significantly increased risk for PCOS.

Major finding: The risk of developing AD was significantly higher in patients with PCOS (adjusted odds ratio [aOR] 1.99; P < .001) than in control participants. Similarly, the risk of developing PCOS was significantly higher in patients with AD (aOR 1.86; P < .001) than in control participants.

Study details: This nested case-control study included 3234 participants with PCOS who were matched with 12,936 control participants without PCOS using nearest-neighbor propensity-score matching, of whom 293 (4.55%) with PCOS and 588 (9.06%) without PCOS had AD.

Disclosures: This study did not disclose any source of funding. The authors declared no conflicts of interest.

Source: Kim IH, Andrade LF, Haq Z, et al. Association of polycystic ovary syndrome with atopic dermatitis: A case control study. Arch Dermatol Res. 2024;316:258. doi: 10.1007/s00403-024-03102-0 Source

Key clinical point: Patients with polycystic ovary syndrome (PCOS) had a significantly increased risk for atopic dermatitis (AD), and patients with AD had a significantly increased risk for PCOS.

Major finding: The risk of developing AD was significantly higher in patients with PCOS (adjusted odds ratio [aOR] 1.99; P < .001) than in control participants. Similarly, the risk of developing PCOS was significantly higher in patients with AD (aOR 1.86; P < .001) than in control participants.

Study details: This nested case-control study included 3234 participants with PCOS who were matched with 12,936 control participants without PCOS using nearest-neighbor propensity-score matching, of whom 293 (4.55%) with PCOS and 588 (9.06%) without PCOS had AD.

Disclosures: This study did not disclose any source of funding. The authors declared no conflicts of interest.

Source: Kim IH, Andrade LF, Haq Z, et al. Association of polycystic ovary syndrome with atopic dermatitis: A case control study. Arch Dermatol Res. 2024;316:258. doi: 10.1007/s00403-024-03102-0 Source

Key clinical point: Patients with moderate to severe atopic dermatitis (AD) who initially responded to a 12-week induction with 200 mg abrocitinib had a low risk for flares during the 40-week maintenance period, irrespective of whether the dose was continued or stepped down to 100 mg.

Major finding: The range of probabilities of not flaring were 6%-82%, 31%-92%, and 14%-34% in patients who received 100 mg abrocitinib, 200 mg abrocitinib, and placebo, respectively. An increased percentage change in the Eczema Area and Severity Index score from baseline to randomization and an Investigator's Global Assessment score of 0 at randomization (both P < .001) were predictors of not flaring.

Study details: This post hoc analysis of the JADE REGIMEN trial included 798 patients with moderate to severe AD who responded to 200 mg abrocitinib induction therapy and were randomly assigned to receive abrocitinib (200 or 100 mg) or placebo during the maintenance period.

Disclosures: This study was funded by Pfizer Inc. Four authors declared being employees and shareholders of Pfizer Inc. Other authors declared having other ties with various sources, including Pfizer Inc.

Source: Thyssen JP, Silverberg JI, Ruano J, et al. Optimizing maintenance therapy in responders to abrocitinib induction: A post hoc analysis of JADE REGIMEN. J Eur Acad Dermatol Venereol. 2024 (May 16). doi: 10.1111/jdv.20095 Source

Key clinical point: Patients with moderate to severe atopic dermatitis (AD) who initially responded to a 12-week induction with 200 mg abrocitinib had a low risk for flares during the 40-week maintenance period, irrespective of whether the dose was continued or stepped down to 100 mg.

Major finding: The range of probabilities of not flaring were 6%-82%, 31%-92%, and 14%-34% in patients who received 100 mg abrocitinib, 200 mg abrocitinib, and placebo, respectively. An increased percentage change in the Eczema Area and Severity Index score from baseline to randomization and an Investigator's Global Assessment score of 0 at randomization (both P < .001) were predictors of not flaring.

Study details: This post hoc analysis of the JADE REGIMEN trial included 798 patients with moderate to severe AD who responded to 200 mg abrocitinib induction therapy and were randomly assigned to receive abrocitinib (200 or 100 mg) or placebo during the maintenance period.

Disclosures: This study was funded by Pfizer Inc. Four authors declared being employees and shareholders of Pfizer Inc. Other authors declared having other ties with various sources, including Pfizer Inc.

Source: Thyssen JP, Silverberg JI, Ruano J, et al. Optimizing maintenance therapy in responders to abrocitinib induction: A post hoc analysis of JADE REGIMEN. J Eur Acad Dermatol Venereol. 2024 (May 16). doi: 10.1111/jdv.20095 Source

Key clinical point: Patients with moderate to severe atopic dermatitis (AD) who initially responded to a 12-week induction with 200 mg abrocitinib had a low risk for flares during the 40-week maintenance period, irrespective of whether the dose was continued or stepped down to 100 mg.

Major finding: The range of probabilities of not flaring were 6%-82%, 31%-92%, and 14%-34% in patients who received 100 mg abrocitinib, 200 mg abrocitinib, and placebo, respectively. An increased percentage change in the Eczema Area and Severity Index score from baseline to randomization and an Investigator's Global Assessment score of 0 at randomization (both P < .001) were predictors of not flaring.

Study details: This post hoc analysis of the JADE REGIMEN trial included 798 patients with moderate to severe AD who responded to 200 mg abrocitinib induction therapy and were randomly assigned to receive abrocitinib (200 or 100 mg) or placebo during the maintenance period.

Disclosures: This study was funded by Pfizer Inc. Four authors declared being employees and shareholders of Pfizer Inc. Other authors declared having other ties with various sources, including Pfizer Inc.

Source: Thyssen JP, Silverberg JI, Ruano J, et al. Optimizing maintenance therapy in responders to abrocitinib induction: A post hoc analysis of JADE REGIMEN. J Eur Acad Dermatol Venereol. 2024 (May 16). doi: 10.1111/jdv.20095 Source