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A 10-year-old with a red bump on her lower lip
The patient’s history and examination are consistent with a diagnosis of pyogenic granuloma. Specifically, the history of rapid growth, friable nature, associated bleeding, and hemorrhagic crusting point to pyogenic granuloma as the most likely diagnosis.
Pyogenic granuloma is an acquired benign vascular growth of the skin or mucous membranes.1 It most frequently occurs in children and young adults and most commonly affects the skin of the head, trunk, and extremities.2 Common mucosal sites include the gingiva, lips, and tongue.2 The etiology of pyogenic granuloma is unknown, though it is thought to be a process akin to the overgrowth of granulation tissue.3,4 Expression of angiogenic factors and subsequent vascular hyperplasia are also implicated as key players in the pathogenesis of pyogenic granuloma.1,4 In addition, several associated factors and inciting triggers have been proposed including trauma, infections, and hormonal fluctuations.3-5 However, the majority of patients do not report predisposing factors or a history of prior trauma at the site.3,6
Clinically, pyogenic granuloma usually presents as a painless, erythematous, dome-shaped friable papule or nodule that easily bleeds and may ulcerate. It typically undergoes a period of growth over weeks to months followed by stabilization. Occasionally, pyogenic granulomas will spontaneously involute, though most do not.7 Pyogenic granuloma may occur within an existing capillary malformation, such as a port wine stain, spontaneously or as a sequela of laser treatment.8,9 Diagnosis of pyogenic granuloma can typically be made clinically on the basis of history and exam. Dermoscopic evaluation of pyogenic granuloma will reveal a homogeneous papule with a surrounding white-brown collarette, and potentially white intersecting lines.10 Histopathologic evaluation may be necessary to differentiate lesions from conditions that may mimic pyogenic granuloma.
What’s on the differential?
The differential diagnosis for pyogenic granuloma consists of Spitz nevus, cherry hemangioma, amelanotic melanoma, and glomus tumor.
Spitz nevus
Spitz nevus (spindle and epithelial cell nevus) is a benign melanocytic lesion that classically appears as a sharply circumscribed, smooth, dome-shaped, pink-red, or brown papule or plaque. There is typically a history of rapid growth over several months followed by stabilization. It usually presents in childhood or adolescence and is most commonly located on the face and extremities. While there are similarities in the appearance of Spitz nevi and pyogenic granuloma, Spitz nevi are not usually friable nor associated with bleeding as in our patient. Furthermore, on dermoscopy, Spitz nevus typically exhibits a starburst pattern with regularly distributed dotted vessels, or a peripheral globular pattern with reticular depigmentation. The definitive diagnosis of Spitz nevi relies on histopathologic evaluation, which is critical for discriminating Spitz nevi from melanoma.
Cherry hemangioma
Cherry angiomas are the most common type of acquired benign vascular proliferation. They present as small, bright red or violaceous macules or papules. However, they typically appear in early to midadulthood and increase in number with age. The age of our patient and solitary presentation of the lesion make this diagnosis unlikely. In addition, cherry angiomas are not usually associated with bleeding. It is important to note that, depending on the age of the patient, pyogenic granuloma may also be confused with infantile hemangioma. Infantile hemangiomas may become bright red papules, nodules, or plaques that appear in early infancy. They characteristically involute, which does not typically happen with pyogenic granuloma.
Amelanotic melanoma
Amelanotic melanoma is an uncommon variant of melanoma with little to no pigmentation. It may appear as a skin-colored to light-brown, pink, or red macule, papule, or nodule. The lesion may be asymmetric with irregular and well-defined borders. The variable and uncharacteristic appearance of this melanoma variant makes it diagnostically challenging and it is often confused with benign lesions including pyogenic granuloma. Dermoscopy can help distinguish amelanotic melanoma from other benign conditions, and will reveal areas of pink to white, polymorphous vessels and crystalline structures. However, ultimately biopsy and histopathological evaluation is necessary for accurate diagnosis.
Glomus tumor
Glomus tumors are rare, benign neoplasms originating from cells of the glomus body that presents as a red-purple, vascular papule or nodule. They are usually found in areas rich in glomus bodies, such as the subungual regions, fingertips, palms, wrists, and forearms. Glomus tumors are typically associated with tenderness, paroxysmal pain, and cold sensitivity. They do not bleed or ulcerate. While pyogenic granuloma may be confused for glomus tumor when present on the fingers or extremities, the location of the lesion in our patient is not consistent with a diagnosis of glomus tumor.
Management and disease course
Management with procedural or topical interventions is usually pursued for pyogenic granuloma because of frequent bleeding and ulceration of lesions. The most common approach is simple excision by a scoop or shave technique, with or without curettage and most commonly with electrocautery of the base. Other options include full-thickness excision, destruction with laser therapy, cryotherapy, or topical treatments (for example, timolol).11 Lesion recurrence can occur with both surgical and nonsurgical management.11 Regardless of management technique, it is useful to obtain histopathologic evaluation of tissue for accurate diagnosis.
Our patient underwent surgical destruction of her lower-lip lesion with shave excision followed by electrocautery. The surgical specimen was sent for pathology, which confirmed the diagnosis of pyogenic granuloma. The patient experienced no complications from the procedure and did not have recurrence of the lesion.
Ms. Sui is a research associate in the department of dermatology, division of pediatric and adolescent dermatology, University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Neither Ms. Sui nor Dr. Eichenfield have any relevant financial disclosures.
References
1. Lin RL and Janniger CK. Cutis. 2004 Oct;74(4):229-33.
2. Harris MN et al. J Am Acad Dermatol. 2000 Jun;42(6):1012-6.
3. Pagliai KA and Cohen BA. Pediatr Dermatol. 2004 Jan-Feb;21(1):10-3.
4. Kamal R et al. J Oral Maxillofac Pathol. 2012 Jan;16(1):79-82.
5. Requena L and Sangueza OP. J Am Acad Dermatol. 1997 Dec;37(6):887-919.
6. Patrice SJ et al. Pediatr Dermatol. 1991 Dec;8(4):267-76.
7. Luba MC et al. Am Fam Physician. 2003 Feb 15;67(4):729-38.
8. Swerlick RA and Cooper PH. J Am Acad Dermatol. 1983 May;8(5):627-30.
9. Sheehan DJ and Lesher JL Jr. Cutis. 2004 Mar;73(3):175-80.
10. Zaballos P et al. Br J Dermatol. 2006 Jun;154(6):1108-11.
11. Lee J et al. J Plast Reconstr Aesthet Surg. 2011 Sep;64(9):1216-20. .
The patient’s history and examination are consistent with a diagnosis of pyogenic granuloma. Specifically, the history of rapid growth, friable nature, associated bleeding, and hemorrhagic crusting point to pyogenic granuloma as the most likely diagnosis.
Pyogenic granuloma is an acquired benign vascular growth of the skin or mucous membranes.1 It most frequently occurs in children and young adults and most commonly affects the skin of the head, trunk, and extremities.2 Common mucosal sites include the gingiva, lips, and tongue.2 The etiology of pyogenic granuloma is unknown, though it is thought to be a process akin to the overgrowth of granulation tissue.3,4 Expression of angiogenic factors and subsequent vascular hyperplasia are also implicated as key players in the pathogenesis of pyogenic granuloma.1,4 In addition, several associated factors and inciting triggers have been proposed including trauma, infections, and hormonal fluctuations.3-5 However, the majority of patients do not report predisposing factors or a history of prior trauma at the site.3,6
Clinically, pyogenic granuloma usually presents as a painless, erythematous, dome-shaped friable papule or nodule that easily bleeds and may ulcerate. It typically undergoes a period of growth over weeks to months followed by stabilization. Occasionally, pyogenic granulomas will spontaneously involute, though most do not.7 Pyogenic granuloma may occur within an existing capillary malformation, such as a port wine stain, spontaneously or as a sequela of laser treatment.8,9 Diagnosis of pyogenic granuloma can typically be made clinically on the basis of history and exam. Dermoscopic evaluation of pyogenic granuloma will reveal a homogeneous papule with a surrounding white-brown collarette, and potentially white intersecting lines.10 Histopathologic evaluation may be necessary to differentiate lesions from conditions that may mimic pyogenic granuloma.
What’s on the differential?
The differential diagnosis for pyogenic granuloma consists of Spitz nevus, cherry hemangioma, amelanotic melanoma, and glomus tumor.
Spitz nevus
Spitz nevus (spindle and epithelial cell nevus) is a benign melanocytic lesion that classically appears as a sharply circumscribed, smooth, dome-shaped, pink-red, or brown papule or plaque. There is typically a history of rapid growth over several months followed by stabilization. It usually presents in childhood or adolescence and is most commonly located on the face and extremities. While there are similarities in the appearance of Spitz nevi and pyogenic granuloma, Spitz nevi are not usually friable nor associated with bleeding as in our patient. Furthermore, on dermoscopy, Spitz nevus typically exhibits a starburst pattern with regularly distributed dotted vessels, or a peripheral globular pattern with reticular depigmentation. The definitive diagnosis of Spitz nevi relies on histopathologic evaluation, which is critical for discriminating Spitz nevi from melanoma.
Cherry hemangioma
Cherry angiomas are the most common type of acquired benign vascular proliferation. They present as small, bright red or violaceous macules or papules. However, they typically appear in early to midadulthood and increase in number with age. The age of our patient and solitary presentation of the lesion make this diagnosis unlikely. In addition, cherry angiomas are not usually associated with bleeding. It is important to note that, depending on the age of the patient, pyogenic granuloma may also be confused with infantile hemangioma. Infantile hemangiomas may become bright red papules, nodules, or plaques that appear in early infancy. They characteristically involute, which does not typically happen with pyogenic granuloma.
Amelanotic melanoma
Amelanotic melanoma is an uncommon variant of melanoma with little to no pigmentation. It may appear as a skin-colored to light-brown, pink, or red macule, papule, or nodule. The lesion may be asymmetric with irregular and well-defined borders. The variable and uncharacteristic appearance of this melanoma variant makes it diagnostically challenging and it is often confused with benign lesions including pyogenic granuloma. Dermoscopy can help distinguish amelanotic melanoma from other benign conditions, and will reveal areas of pink to white, polymorphous vessels and crystalline structures. However, ultimately biopsy and histopathological evaluation is necessary for accurate diagnosis.
Glomus tumor
Glomus tumors are rare, benign neoplasms originating from cells of the glomus body that presents as a red-purple, vascular papule or nodule. They are usually found in areas rich in glomus bodies, such as the subungual regions, fingertips, palms, wrists, and forearms. Glomus tumors are typically associated with tenderness, paroxysmal pain, and cold sensitivity. They do not bleed or ulcerate. While pyogenic granuloma may be confused for glomus tumor when present on the fingers or extremities, the location of the lesion in our patient is not consistent with a diagnosis of glomus tumor.
Management and disease course
Management with procedural or topical interventions is usually pursued for pyogenic granuloma because of frequent bleeding and ulceration of lesions. The most common approach is simple excision by a scoop or shave technique, with or without curettage and most commonly with electrocautery of the base. Other options include full-thickness excision, destruction with laser therapy, cryotherapy, or topical treatments (for example, timolol).11 Lesion recurrence can occur with both surgical and nonsurgical management.11 Regardless of management technique, it is useful to obtain histopathologic evaluation of tissue for accurate diagnosis.
Our patient underwent surgical destruction of her lower-lip lesion with shave excision followed by electrocautery. The surgical specimen was sent for pathology, which confirmed the diagnosis of pyogenic granuloma. The patient experienced no complications from the procedure and did not have recurrence of the lesion.
Ms. Sui is a research associate in the department of dermatology, division of pediatric and adolescent dermatology, University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Neither Ms. Sui nor Dr. Eichenfield have any relevant financial disclosures.
References
1. Lin RL and Janniger CK. Cutis. 2004 Oct;74(4):229-33.
2. Harris MN et al. J Am Acad Dermatol. 2000 Jun;42(6):1012-6.
3. Pagliai KA and Cohen BA. Pediatr Dermatol. 2004 Jan-Feb;21(1):10-3.
4. Kamal R et al. J Oral Maxillofac Pathol. 2012 Jan;16(1):79-82.
5. Requena L and Sangueza OP. J Am Acad Dermatol. 1997 Dec;37(6):887-919.
6. Patrice SJ et al. Pediatr Dermatol. 1991 Dec;8(4):267-76.
7. Luba MC et al. Am Fam Physician. 2003 Feb 15;67(4):729-38.
8. Swerlick RA and Cooper PH. J Am Acad Dermatol. 1983 May;8(5):627-30.
9. Sheehan DJ and Lesher JL Jr. Cutis. 2004 Mar;73(3):175-80.
10. Zaballos P et al. Br J Dermatol. 2006 Jun;154(6):1108-11.
11. Lee J et al. J Plast Reconstr Aesthet Surg. 2011 Sep;64(9):1216-20. .
The patient’s history and examination are consistent with a diagnosis of pyogenic granuloma. Specifically, the history of rapid growth, friable nature, associated bleeding, and hemorrhagic crusting point to pyogenic granuloma as the most likely diagnosis.
Pyogenic granuloma is an acquired benign vascular growth of the skin or mucous membranes.1 It most frequently occurs in children and young adults and most commonly affects the skin of the head, trunk, and extremities.2 Common mucosal sites include the gingiva, lips, and tongue.2 The etiology of pyogenic granuloma is unknown, though it is thought to be a process akin to the overgrowth of granulation tissue.3,4 Expression of angiogenic factors and subsequent vascular hyperplasia are also implicated as key players in the pathogenesis of pyogenic granuloma.1,4 In addition, several associated factors and inciting triggers have been proposed including trauma, infections, and hormonal fluctuations.3-5 However, the majority of patients do not report predisposing factors or a history of prior trauma at the site.3,6
Clinically, pyogenic granuloma usually presents as a painless, erythematous, dome-shaped friable papule or nodule that easily bleeds and may ulcerate. It typically undergoes a period of growth over weeks to months followed by stabilization. Occasionally, pyogenic granulomas will spontaneously involute, though most do not.7 Pyogenic granuloma may occur within an existing capillary malformation, such as a port wine stain, spontaneously or as a sequela of laser treatment.8,9 Diagnosis of pyogenic granuloma can typically be made clinically on the basis of history and exam. Dermoscopic evaluation of pyogenic granuloma will reveal a homogeneous papule with a surrounding white-brown collarette, and potentially white intersecting lines.10 Histopathologic evaluation may be necessary to differentiate lesions from conditions that may mimic pyogenic granuloma.
What’s on the differential?
The differential diagnosis for pyogenic granuloma consists of Spitz nevus, cherry hemangioma, amelanotic melanoma, and glomus tumor.
Spitz nevus
Spitz nevus (spindle and epithelial cell nevus) is a benign melanocytic lesion that classically appears as a sharply circumscribed, smooth, dome-shaped, pink-red, or brown papule or plaque. There is typically a history of rapid growth over several months followed by stabilization. It usually presents in childhood or adolescence and is most commonly located on the face and extremities. While there are similarities in the appearance of Spitz nevi and pyogenic granuloma, Spitz nevi are not usually friable nor associated with bleeding as in our patient. Furthermore, on dermoscopy, Spitz nevus typically exhibits a starburst pattern with regularly distributed dotted vessels, or a peripheral globular pattern with reticular depigmentation. The definitive diagnosis of Spitz nevi relies on histopathologic evaluation, which is critical for discriminating Spitz nevi from melanoma.
Cherry hemangioma
Cherry angiomas are the most common type of acquired benign vascular proliferation. They present as small, bright red or violaceous macules or papules. However, they typically appear in early to midadulthood and increase in number with age. The age of our patient and solitary presentation of the lesion make this diagnosis unlikely. In addition, cherry angiomas are not usually associated with bleeding. It is important to note that, depending on the age of the patient, pyogenic granuloma may also be confused with infantile hemangioma. Infantile hemangiomas may become bright red papules, nodules, or plaques that appear in early infancy. They characteristically involute, which does not typically happen with pyogenic granuloma.
Amelanotic melanoma
Amelanotic melanoma is an uncommon variant of melanoma with little to no pigmentation. It may appear as a skin-colored to light-brown, pink, or red macule, papule, or nodule. The lesion may be asymmetric with irregular and well-defined borders. The variable and uncharacteristic appearance of this melanoma variant makes it diagnostically challenging and it is often confused with benign lesions including pyogenic granuloma. Dermoscopy can help distinguish amelanotic melanoma from other benign conditions, and will reveal areas of pink to white, polymorphous vessels and crystalline structures. However, ultimately biopsy and histopathological evaluation is necessary for accurate diagnosis.
Glomus tumor
Glomus tumors are rare, benign neoplasms originating from cells of the glomus body that presents as a red-purple, vascular papule or nodule. They are usually found in areas rich in glomus bodies, such as the subungual regions, fingertips, palms, wrists, and forearms. Glomus tumors are typically associated with tenderness, paroxysmal pain, and cold sensitivity. They do not bleed or ulcerate. While pyogenic granuloma may be confused for glomus tumor when present on the fingers or extremities, the location of the lesion in our patient is not consistent with a diagnosis of glomus tumor.
Management and disease course
Management with procedural or topical interventions is usually pursued for pyogenic granuloma because of frequent bleeding and ulceration of lesions. The most common approach is simple excision by a scoop or shave technique, with or without curettage and most commonly with electrocautery of the base. Other options include full-thickness excision, destruction with laser therapy, cryotherapy, or topical treatments (for example, timolol).11 Lesion recurrence can occur with both surgical and nonsurgical management.11 Regardless of management technique, it is useful to obtain histopathologic evaluation of tissue for accurate diagnosis.
Our patient underwent surgical destruction of her lower-lip lesion with shave excision followed by electrocautery. The surgical specimen was sent for pathology, which confirmed the diagnosis of pyogenic granuloma. The patient experienced no complications from the procedure and did not have recurrence of the lesion.
Ms. Sui is a research associate in the department of dermatology, division of pediatric and adolescent dermatology, University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Neither Ms. Sui nor Dr. Eichenfield have any relevant financial disclosures.
References
1. Lin RL and Janniger CK. Cutis. 2004 Oct;74(4):229-33.
2. Harris MN et al. J Am Acad Dermatol. 2000 Jun;42(6):1012-6.
3. Pagliai KA and Cohen BA. Pediatr Dermatol. 2004 Jan-Feb;21(1):10-3.
4. Kamal R et al. J Oral Maxillofac Pathol. 2012 Jan;16(1):79-82.
5. Requena L and Sangueza OP. J Am Acad Dermatol. 1997 Dec;37(6):887-919.
6. Patrice SJ et al. Pediatr Dermatol. 1991 Dec;8(4):267-76.
7. Luba MC et al. Am Fam Physician. 2003 Feb 15;67(4):729-38.
8. Swerlick RA and Cooper PH. J Am Acad Dermatol. 1983 May;8(5):627-30.
9. Sheehan DJ and Lesher JL Jr. Cutis. 2004 Mar;73(3):175-80.
10. Zaballos P et al. Br J Dermatol. 2006 Jun;154(6):1108-11.
11. Lee J et al. J Plast Reconstr Aesthet Surg. 2011 Sep;64(9):1216-20. .
Apremilast alleviates severe psoriasis in some children, data show
not controlled by topical therapy, according to the results of a phase 3 trial.
“Unfortunately, there are limited treatment options for pediatric patients with moderate to severe plaque psoriasis” who do not respond to or cannot use topical therapy, said study investigator Anna Belloni Fortina, MD, speaking at the annual meeting of the European Academy of Dermatology and Venereology.
“In this randomized, placebo-controlled trial, oral apremilast demonstrated effectiveness and was well tolerated,” added Dr. Belloni Fortina, of Azienda Ospedale Università Padova (Italy). “I underline oral because for children, oral administration is better than the injection treatment.”
Key findings
Dubbed the SPROUT study, the trial set a primary endpoint of the percentage of children with a Physician’s Global Assessment (sPGA) response after 16 weeks of treatment or placebo. The sPGA is a 5-point scale ranging from 0 (clear) to 4 (severe). The study enrolled children with an sPGA greater than or equal to 3. Response was defined as a sPGA score of 0 or 1, indicating clear or almost clear skin, with at least a 2-point reduction from baseline values.
At week 16, the primary endpoint was met by 33% of 163 children treated with apremilast versus 11% of 82 children who had been given a placebo, a treatment difference of 21.7% (95% confidence interval, 11.2%-32.1%).
A greater proportion of children treated with apremilast also achieved a major secondary endpoint, a 75% or greater reduction in the Psoriasis Area and Severity Index (PASI-75) (45.4% vs. 16.1%), a treatment difference of 29.4% (95% CI, 17.8%-40.9%).
Results unaffected by weight and age
Regarding apremilast, “it’s important to underline that patients were dosed according to their weight,” Dr. Belloni Fortina said.
A dose of 20 mg twice daily was given to children who weighed between 20 kg and less than 50 kg, and a 30-mg twice-daily dose was given to those who weighed greater than or equal to 50 kg.
When the data were analyzed according to weight, proportionately more children on apremilast saw a sPGA response: 47.4% versus 21.8% in the lower weight and dose range and 19.2% versus 1.6% in the higher weight and dose range.
As for PASI-75, a greater proportion of children on apremilast also responded in both the lower and upper weight ranges, a respective 52.4% and 38.7% of patients, compared with 21.4% and 11% of those treated with placebo.
Data were also evaluated according to age, with a younger (aged 6-11 years) and older (age 12-17 years) group. The mean age of children was 12 years overall. Results showed a similar pattern for weight: The psoriasis of more children treated with apremilast was reduced by both measures, sPGA response, and PASI-75.
Safety of apremilast in children
“The overall safety profile during the placebo-controlled phase was comparable with the known safety profile of apremilast,” Dr. Belloni Fontina reported. “No new safety signals were identified.”
The rate of any adverse event was substantially higher in children given the active treatment, however, at 65% versus 41.3% for placebo.
Rates of severe and serious adverse events were low, at around 1.3%, and similar between the groups.
There was also a low rate of withdrawal because of side effects, although this was higher in the apremilast group (3.1% vs. 1.3%).
The primary reason for withdrawal of apremilast treatment were the most commonly reported adverse events: gastrointestinal disorders, including diarrhea, nausea, upper and lower abdominal pain, and vomiting. Headache, pyrexia, and nasopharyngitis were also reported.
Despite being common, most treatment-related adverse effects resolved within 3 days, Dr. Belloni Fontina said.
Expect further data
Further data from the trial are to be expected, because only the 16-week primary endpoint results have been released so far. The trial also included a 36-week extension phase, during which all children who had originally been randomly assigned to placebo were now eligible to be treated with apremilast, and all those who were originally given the active treatment were able to continue. This extension treatment period means that data will be available for a full year of treatment, and there will also be a further 2-week observational follow-up at the end of the trial.
The study was funded by Amgen. Dr. Belloni Fontina reported acting as an investigator and advisory board member for and receiving honoraria from Amgen, Galderma, Leo Pharma, and Pfizer. She also reported speaking on behalf of Pierre-Fabre and Galderma.
A version of this article first appeared on Medscape.com.
not controlled by topical therapy, according to the results of a phase 3 trial.
“Unfortunately, there are limited treatment options for pediatric patients with moderate to severe plaque psoriasis” who do not respond to or cannot use topical therapy, said study investigator Anna Belloni Fortina, MD, speaking at the annual meeting of the European Academy of Dermatology and Venereology.
“In this randomized, placebo-controlled trial, oral apremilast demonstrated effectiveness and was well tolerated,” added Dr. Belloni Fortina, of Azienda Ospedale Università Padova (Italy). “I underline oral because for children, oral administration is better than the injection treatment.”
Key findings
Dubbed the SPROUT study, the trial set a primary endpoint of the percentage of children with a Physician’s Global Assessment (sPGA) response after 16 weeks of treatment or placebo. The sPGA is a 5-point scale ranging from 0 (clear) to 4 (severe). The study enrolled children with an sPGA greater than or equal to 3. Response was defined as a sPGA score of 0 or 1, indicating clear or almost clear skin, with at least a 2-point reduction from baseline values.
At week 16, the primary endpoint was met by 33% of 163 children treated with apremilast versus 11% of 82 children who had been given a placebo, a treatment difference of 21.7% (95% confidence interval, 11.2%-32.1%).
A greater proportion of children treated with apremilast also achieved a major secondary endpoint, a 75% or greater reduction in the Psoriasis Area and Severity Index (PASI-75) (45.4% vs. 16.1%), a treatment difference of 29.4% (95% CI, 17.8%-40.9%).
Results unaffected by weight and age
Regarding apremilast, “it’s important to underline that patients were dosed according to their weight,” Dr. Belloni Fortina said.
A dose of 20 mg twice daily was given to children who weighed between 20 kg and less than 50 kg, and a 30-mg twice-daily dose was given to those who weighed greater than or equal to 50 kg.
When the data were analyzed according to weight, proportionately more children on apremilast saw a sPGA response: 47.4% versus 21.8% in the lower weight and dose range and 19.2% versus 1.6% in the higher weight and dose range.
As for PASI-75, a greater proportion of children on apremilast also responded in both the lower and upper weight ranges, a respective 52.4% and 38.7% of patients, compared with 21.4% and 11% of those treated with placebo.
Data were also evaluated according to age, with a younger (aged 6-11 years) and older (age 12-17 years) group. The mean age of children was 12 years overall. Results showed a similar pattern for weight: The psoriasis of more children treated with apremilast was reduced by both measures, sPGA response, and PASI-75.
Safety of apremilast in children
“The overall safety profile during the placebo-controlled phase was comparable with the known safety profile of apremilast,” Dr. Belloni Fontina reported. “No new safety signals were identified.”
The rate of any adverse event was substantially higher in children given the active treatment, however, at 65% versus 41.3% for placebo.
Rates of severe and serious adverse events were low, at around 1.3%, and similar between the groups.
There was also a low rate of withdrawal because of side effects, although this was higher in the apremilast group (3.1% vs. 1.3%).
The primary reason for withdrawal of apremilast treatment were the most commonly reported adverse events: gastrointestinal disorders, including diarrhea, nausea, upper and lower abdominal pain, and vomiting. Headache, pyrexia, and nasopharyngitis were also reported.
Despite being common, most treatment-related adverse effects resolved within 3 days, Dr. Belloni Fontina said.
Expect further data
Further data from the trial are to be expected, because only the 16-week primary endpoint results have been released so far. The trial also included a 36-week extension phase, during which all children who had originally been randomly assigned to placebo were now eligible to be treated with apremilast, and all those who were originally given the active treatment were able to continue. This extension treatment period means that data will be available for a full year of treatment, and there will also be a further 2-week observational follow-up at the end of the trial.
The study was funded by Amgen. Dr. Belloni Fontina reported acting as an investigator and advisory board member for and receiving honoraria from Amgen, Galderma, Leo Pharma, and Pfizer. She also reported speaking on behalf of Pierre-Fabre and Galderma.
A version of this article first appeared on Medscape.com.
not controlled by topical therapy, according to the results of a phase 3 trial.
“Unfortunately, there are limited treatment options for pediatric patients with moderate to severe plaque psoriasis” who do not respond to or cannot use topical therapy, said study investigator Anna Belloni Fortina, MD, speaking at the annual meeting of the European Academy of Dermatology and Venereology.
“In this randomized, placebo-controlled trial, oral apremilast demonstrated effectiveness and was well tolerated,” added Dr. Belloni Fortina, of Azienda Ospedale Università Padova (Italy). “I underline oral because for children, oral administration is better than the injection treatment.”
Key findings
Dubbed the SPROUT study, the trial set a primary endpoint of the percentage of children with a Physician’s Global Assessment (sPGA) response after 16 weeks of treatment or placebo. The sPGA is a 5-point scale ranging from 0 (clear) to 4 (severe). The study enrolled children with an sPGA greater than or equal to 3. Response was defined as a sPGA score of 0 or 1, indicating clear or almost clear skin, with at least a 2-point reduction from baseline values.
At week 16, the primary endpoint was met by 33% of 163 children treated with apremilast versus 11% of 82 children who had been given a placebo, a treatment difference of 21.7% (95% confidence interval, 11.2%-32.1%).
A greater proportion of children treated with apremilast also achieved a major secondary endpoint, a 75% or greater reduction in the Psoriasis Area and Severity Index (PASI-75) (45.4% vs. 16.1%), a treatment difference of 29.4% (95% CI, 17.8%-40.9%).
Results unaffected by weight and age
Regarding apremilast, “it’s important to underline that patients were dosed according to their weight,” Dr. Belloni Fortina said.
A dose of 20 mg twice daily was given to children who weighed between 20 kg and less than 50 kg, and a 30-mg twice-daily dose was given to those who weighed greater than or equal to 50 kg.
When the data were analyzed according to weight, proportionately more children on apremilast saw a sPGA response: 47.4% versus 21.8% in the lower weight and dose range and 19.2% versus 1.6% in the higher weight and dose range.
As for PASI-75, a greater proportion of children on apremilast also responded in both the lower and upper weight ranges, a respective 52.4% and 38.7% of patients, compared with 21.4% and 11% of those treated with placebo.
Data were also evaluated according to age, with a younger (aged 6-11 years) and older (age 12-17 years) group. The mean age of children was 12 years overall. Results showed a similar pattern for weight: The psoriasis of more children treated with apremilast was reduced by both measures, sPGA response, and PASI-75.
Safety of apremilast in children
“The overall safety profile during the placebo-controlled phase was comparable with the known safety profile of apremilast,” Dr. Belloni Fontina reported. “No new safety signals were identified.”
The rate of any adverse event was substantially higher in children given the active treatment, however, at 65% versus 41.3% for placebo.
Rates of severe and serious adverse events were low, at around 1.3%, and similar between the groups.
There was also a low rate of withdrawal because of side effects, although this was higher in the apremilast group (3.1% vs. 1.3%).
The primary reason for withdrawal of apremilast treatment were the most commonly reported adverse events: gastrointestinal disorders, including diarrhea, nausea, upper and lower abdominal pain, and vomiting. Headache, pyrexia, and nasopharyngitis were also reported.
Despite being common, most treatment-related adverse effects resolved within 3 days, Dr. Belloni Fontina said.
Expect further data
Further data from the trial are to be expected, because only the 16-week primary endpoint results have been released so far. The trial also included a 36-week extension phase, during which all children who had originally been randomly assigned to placebo were now eligible to be treated with apremilast, and all those who were originally given the active treatment were able to continue. This extension treatment period means that data will be available for a full year of treatment, and there will also be a further 2-week observational follow-up at the end of the trial.
The study was funded by Amgen. Dr. Belloni Fontina reported acting as an investigator and advisory board member for and receiving honoraria from Amgen, Galderma, Leo Pharma, and Pfizer. She also reported speaking on behalf of Pierre-Fabre and Galderma.
A version of this article first appeared on Medscape.com.
FROM EADV 2022
Uncombable hair syndrome: One gene, variants responsible for many cases
that manifests during infancy, investigators have reported.
The findings are from a cohort study published in JAMA Dermatology, which involved 107 unrelated children and adults suspected of having UHS, as well as family members, all of whom were recruited from January 2013 to December 2021. Genetic analyses were conducted in Germany from January 2014 to December 2021 with exome sequencing.
Study builds on prior research
Senior author Regina C. Betz, MD, professor of dermatogenetics at the Institute of Human Genetics, University Hospital Bonn, Germany, said that in 2016, she and her coinvestigators authored a study on the molecular genetics of UHS. That study, which involved 18 people with UHS, identified variants in three genes – PADI3, TCHH, and TGM3 – that encode proteins that play a role in the formation of the hair shaft. The investigators described how a deficiency in the shaping and mechanical strengthening of the hair shaft occurs in the UHS phenotype, which is characterized by dry, frizzy, and wiry hair that cannot be combed flat.
As a result of that previous work, “we base the assignment or confirmation of a clinical diagnosis of UHS on molecular genetic diagnostics,” the authors write in the new study, rather than on the clinical appearance of the hair and the physical examination of the patient, with confirmation on microscopical examination of the hair shaft.
Social media as instrument in finding study participants
Following the 2016 study, Dr. Betz and colleagues were contacted by many clinicians and by the public through Facebook and other social media platforms with details about possible cases of UHS, an autosomal recessive disorder. Through these contacts, blood samples, saliva, or DNA was sent to the investigators’ laboratory from 89 unrelated index patients (69 female patients, 20 male patients) suspected of having UHS. This resulted in the identification of pathogenic variants in 69 cases, the investigators write.
“In the first study, we had 18 patients, and then we tried to collect as many as possible” to determine the main mechanism behind UHS, Dr. Betz said. One question is whether there are additional genes responsible for UHS, she noted. “Even now, we are not sure, because in 25% [of cases in the new study], we didn’t find any mutation in the three known genes.”
The current study resulted in the discovery of eight novel pathogenic variants in PADI3, which are responsible for 71.0% (76) of the 107 cases. Of those, “6 were single observations and 2 were observed in 3 and 2 individuals, respectively,” the investigators write.
Children can grow out of this disorder, but it can also persist into adulthood, Dr. Betz noted. Communication that investigators had with parents of the children with UHS revealed that these children are often the targets of bullying by other children, she added.
She and her and colleagues will continue this research and are currently studying adults who have UHS.
Research leads to possible treatment pathways
Jeff Donovan, MD, FRCPC, FAAD, a dermatologist and medical director of the Donovan Hair Clinic in Whistler, British Columbia, described these findings as fundamental to understanding UHS and creating pathways to possible treatments.
The study “identifies more about the genetic basis of this challenging condition,” said Dr. Donovan, who is also clinical instructor in the department of dermatology at the University of British Columbia, Vancouver, and president of the Canadian Hair Loss Foundation. “We really need this type of information in order to have any sort of clue in terms of how to treat it,” he told this news organization.
“In the hair loss world, it’s pretty clear that if you can understand the genetic basis of things, or the basic science of a condition, whether it’s the basic genetics or the basic immunology, you give yourself the best chance to develop good treatments,” said Dr. Donovan.
The article provides advanced genetic information of the condition, such that geneticists can test for at least three markers if they are suspecting UHS, Dr. Donovan observed.
Condition can lead to bullying
Dr. Donovan also commented that UHS can have a detrimental impact on children with regard to socializing with their peers. “Having hair that sticks out and is very full like this is challenging because kids do get teased,” he said.
“It is often the parents who are the most affected” when a child aged 2-5 years has a hair condition such as UHS. But at age 5-9, “children are developing self-identity and an understanding of various aspects of self-esteem and what they look like and what others look like. And that’s where the teasing really starts. And that’s where it does become troublesome.”
Dr. Betz and Dr. Donovan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
that manifests during infancy, investigators have reported.
The findings are from a cohort study published in JAMA Dermatology, which involved 107 unrelated children and adults suspected of having UHS, as well as family members, all of whom were recruited from January 2013 to December 2021. Genetic analyses were conducted in Germany from January 2014 to December 2021 with exome sequencing.
Study builds on prior research
Senior author Regina C. Betz, MD, professor of dermatogenetics at the Institute of Human Genetics, University Hospital Bonn, Germany, said that in 2016, she and her coinvestigators authored a study on the molecular genetics of UHS. That study, which involved 18 people with UHS, identified variants in three genes – PADI3, TCHH, and TGM3 – that encode proteins that play a role in the formation of the hair shaft. The investigators described how a deficiency in the shaping and mechanical strengthening of the hair shaft occurs in the UHS phenotype, which is characterized by dry, frizzy, and wiry hair that cannot be combed flat.
As a result of that previous work, “we base the assignment or confirmation of a clinical diagnosis of UHS on molecular genetic diagnostics,” the authors write in the new study, rather than on the clinical appearance of the hair and the physical examination of the patient, with confirmation on microscopical examination of the hair shaft.
Social media as instrument in finding study participants
Following the 2016 study, Dr. Betz and colleagues were contacted by many clinicians and by the public through Facebook and other social media platforms with details about possible cases of UHS, an autosomal recessive disorder. Through these contacts, blood samples, saliva, or DNA was sent to the investigators’ laboratory from 89 unrelated index patients (69 female patients, 20 male patients) suspected of having UHS. This resulted in the identification of pathogenic variants in 69 cases, the investigators write.
“In the first study, we had 18 patients, and then we tried to collect as many as possible” to determine the main mechanism behind UHS, Dr. Betz said. One question is whether there are additional genes responsible for UHS, she noted. “Even now, we are not sure, because in 25% [of cases in the new study], we didn’t find any mutation in the three known genes.”
The current study resulted in the discovery of eight novel pathogenic variants in PADI3, which are responsible for 71.0% (76) of the 107 cases. Of those, “6 were single observations and 2 were observed in 3 and 2 individuals, respectively,” the investigators write.
Children can grow out of this disorder, but it can also persist into adulthood, Dr. Betz noted. Communication that investigators had with parents of the children with UHS revealed that these children are often the targets of bullying by other children, she added.
She and her and colleagues will continue this research and are currently studying adults who have UHS.
Research leads to possible treatment pathways
Jeff Donovan, MD, FRCPC, FAAD, a dermatologist and medical director of the Donovan Hair Clinic in Whistler, British Columbia, described these findings as fundamental to understanding UHS and creating pathways to possible treatments.
The study “identifies more about the genetic basis of this challenging condition,” said Dr. Donovan, who is also clinical instructor in the department of dermatology at the University of British Columbia, Vancouver, and president of the Canadian Hair Loss Foundation. “We really need this type of information in order to have any sort of clue in terms of how to treat it,” he told this news organization.
“In the hair loss world, it’s pretty clear that if you can understand the genetic basis of things, or the basic science of a condition, whether it’s the basic genetics or the basic immunology, you give yourself the best chance to develop good treatments,” said Dr. Donovan.
The article provides advanced genetic information of the condition, such that geneticists can test for at least three markers if they are suspecting UHS, Dr. Donovan observed.
Condition can lead to bullying
Dr. Donovan also commented that UHS can have a detrimental impact on children with regard to socializing with their peers. “Having hair that sticks out and is very full like this is challenging because kids do get teased,” he said.
“It is often the parents who are the most affected” when a child aged 2-5 years has a hair condition such as UHS. But at age 5-9, “children are developing self-identity and an understanding of various aspects of self-esteem and what they look like and what others look like. And that’s where the teasing really starts. And that’s where it does become troublesome.”
Dr. Betz and Dr. Donovan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
that manifests during infancy, investigators have reported.
The findings are from a cohort study published in JAMA Dermatology, which involved 107 unrelated children and adults suspected of having UHS, as well as family members, all of whom were recruited from January 2013 to December 2021. Genetic analyses were conducted in Germany from January 2014 to December 2021 with exome sequencing.
Study builds on prior research
Senior author Regina C. Betz, MD, professor of dermatogenetics at the Institute of Human Genetics, University Hospital Bonn, Germany, said that in 2016, she and her coinvestigators authored a study on the molecular genetics of UHS. That study, which involved 18 people with UHS, identified variants in three genes – PADI3, TCHH, and TGM3 – that encode proteins that play a role in the formation of the hair shaft. The investigators described how a deficiency in the shaping and mechanical strengthening of the hair shaft occurs in the UHS phenotype, which is characterized by dry, frizzy, and wiry hair that cannot be combed flat.
As a result of that previous work, “we base the assignment or confirmation of a clinical diagnosis of UHS on molecular genetic diagnostics,” the authors write in the new study, rather than on the clinical appearance of the hair and the physical examination of the patient, with confirmation on microscopical examination of the hair shaft.
Social media as instrument in finding study participants
Following the 2016 study, Dr. Betz and colleagues were contacted by many clinicians and by the public through Facebook and other social media platforms with details about possible cases of UHS, an autosomal recessive disorder. Through these contacts, blood samples, saliva, or DNA was sent to the investigators’ laboratory from 89 unrelated index patients (69 female patients, 20 male patients) suspected of having UHS. This resulted in the identification of pathogenic variants in 69 cases, the investigators write.
“In the first study, we had 18 patients, and then we tried to collect as many as possible” to determine the main mechanism behind UHS, Dr. Betz said. One question is whether there are additional genes responsible for UHS, she noted. “Even now, we are not sure, because in 25% [of cases in the new study], we didn’t find any mutation in the three known genes.”
The current study resulted in the discovery of eight novel pathogenic variants in PADI3, which are responsible for 71.0% (76) of the 107 cases. Of those, “6 were single observations and 2 were observed in 3 and 2 individuals, respectively,” the investigators write.
Children can grow out of this disorder, but it can also persist into adulthood, Dr. Betz noted. Communication that investigators had with parents of the children with UHS revealed that these children are often the targets of bullying by other children, she added.
She and her and colleagues will continue this research and are currently studying adults who have UHS.
Research leads to possible treatment pathways
Jeff Donovan, MD, FRCPC, FAAD, a dermatologist and medical director of the Donovan Hair Clinic in Whistler, British Columbia, described these findings as fundamental to understanding UHS and creating pathways to possible treatments.
The study “identifies more about the genetic basis of this challenging condition,” said Dr. Donovan, who is also clinical instructor in the department of dermatology at the University of British Columbia, Vancouver, and president of the Canadian Hair Loss Foundation. “We really need this type of information in order to have any sort of clue in terms of how to treat it,” he told this news organization.
“In the hair loss world, it’s pretty clear that if you can understand the genetic basis of things, or the basic science of a condition, whether it’s the basic genetics or the basic immunology, you give yourself the best chance to develop good treatments,” said Dr. Donovan.
The article provides advanced genetic information of the condition, such that geneticists can test for at least three markers if they are suspecting UHS, Dr. Donovan observed.
Condition can lead to bullying
Dr. Donovan also commented that UHS can have a detrimental impact on children with regard to socializing with their peers. “Having hair that sticks out and is very full like this is challenging because kids do get teased,” he said.
“It is often the parents who are the most affected” when a child aged 2-5 years has a hair condition such as UHS. But at age 5-9, “children are developing self-identity and an understanding of various aspects of self-esteem and what they look like and what others look like. And that’s where the teasing really starts. And that’s where it does become troublesome.”
Dr. Betz and Dr. Donovan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA DERMATOLOGY
Tralokinumab earns EU recommendation to expand age range for atopic dermatitis to include adolescents
Tralokinumab has received a positive opinion from the European Medicine Agency’s Committee for Medicinal Products for Human Use to extend use to adolescents aged 12 years and older with moderate-to-severe atopic dermatitis (AD) who are candidates for systemic therapy, according to a statement from the manufacturer.
The positive CHMP opinion, issued on Sept. 15, recommends extending the use of tralokinumab (Adtralza), an interleukin-13 antagonist, to adolescents aged 12-17 years in the EU. The positive opinion recommends an initial dose of 600 mg administered subcutaneously followed by 300 mg every other week, the dosing recommended for adults.
In December 2021, tralokinumab was approved for adults with moderate to severe AD in the United States, where it is marketed as Adbry. It is also approved for adults in the EU, Great Britain, Canada, the United Arab Emirates, and Switzerland. It is not currently approved for treatment of adolescents in any country, according to the LEO Pharma statement.
A regulatory filing with the U.S. Food and Drug Administration is in progress, the company said, and an additional study of tralokinumab for individuals aged 12 years and older is underway, according to the manufacturer.
The CHMP opinion was supported by data from a phase 3 study (ECZTRA 6) that assessed safety and efficacy of 150-mg or 300-mg doses of tralokinumab, compared with placebo in adolescents with moderate-to-severe AD, the company statement said. The primary outcomes were an Investigator Global Assessment score of clear or almost clear skin (IGA 0/1) and an improvement of at least a 75% on the Eczema Area and Severity Index score (EASI-75). In the study, presented as a poster at a meeting in October 2021, a total of 195 adolescents aged 12-17 with moderate to severe AD who were candidates for systemic therapy were randomly assigned to tralokinumab and 94 to placebo.
At 16 weeks, 21.4% and 17.5% of patients who received 150 mg and 300 mg, respectively, of tralokinumab had IGA scores of 0 or 1, compared with 4.3% of those on placebo (P < .001, P = .002, respectively vs. placebo). In addition, 28.6% and 27.8% of the 150-mg and 300-mg tralokinumab groups, respectively, achieved EASI-75, compared with 6.4% of placebo patients (P < .001, P = .001, respectively, compared with placebo).
Adverse events were similar between the groups, and most were mild or moderate; overall safety profiles were similar to those seen in adult patients.
The European Commission will review the positive opinion and make a final decision.
The research was supported by LEO Pharma.
A version of this article first appeared on Medscape.com.
Tralokinumab has received a positive opinion from the European Medicine Agency’s Committee for Medicinal Products for Human Use to extend use to adolescents aged 12 years and older with moderate-to-severe atopic dermatitis (AD) who are candidates for systemic therapy, according to a statement from the manufacturer.
The positive CHMP opinion, issued on Sept. 15, recommends extending the use of tralokinumab (Adtralza), an interleukin-13 antagonist, to adolescents aged 12-17 years in the EU. The positive opinion recommends an initial dose of 600 mg administered subcutaneously followed by 300 mg every other week, the dosing recommended for adults.
In December 2021, tralokinumab was approved for adults with moderate to severe AD in the United States, where it is marketed as Adbry. It is also approved for adults in the EU, Great Britain, Canada, the United Arab Emirates, and Switzerland. It is not currently approved for treatment of adolescents in any country, according to the LEO Pharma statement.
A regulatory filing with the U.S. Food and Drug Administration is in progress, the company said, and an additional study of tralokinumab for individuals aged 12 years and older is underway, according to the manufacturer.
The CHMP opinion was supported by data from a phase 3 study (ECZTRA 6) that assessed safety and efficacy of 150-mg or 300-mg doses of tralokinumab, compared with placebo in adolescents with moderate-to-severe AD, the company statement said. The primary outcomes were an Investigator Global Assessment score of clear or almost clear skin (IGA 0/1) and an improvement of at least a 75% on the Eczema Area and Severity Index score (EASI-75). In the study, presented as a poster at a meeting in October 2021, a total of 195 adolescents aged 12-17 with moderate to severe AD who were candidates for systemic therapy were randomly assigned to tralokinumab and 94 to placebo.
At 16 weeks, 21.4% and 17.5% of patients who received 150 mg and 300 mg, respectively, of tralokinumab had IGA scores of 0 or 1, compared with 4.3% of those on placebo (P < .001, P = .002, respectively vs. placebo). In addition, 28.6% and 27.8% of the 150-mg and 300-mg tralokinumab groups, respectively, achieved EASI-75, compared with 6.4% of placebo patients (P < .001, P = .001, respectively, compared with placebo).
Adverse events were similar between the groups, and most were mild or moderate; overall safety profiles were similar to those seen in adult patients.
The European Commission will review the positive opinion and make a final decision.
The research was supported by LEO Pharma.
A version of this article first appeared on Medscape.com.
Tralokinumab has received a positive opinion from the European Medicine Agency’s Committee for Medicinal Products for Human Use to extend use to adolescents aged 12 years and older with moderate-to-severe atopic dermatitis (AD) who are candidates for systemic therapy, according to a statement from the manufacturer.
The positive CHMP opinion, issued on Sept. 15, recommends extending the use of tralokinumab (Adtralza), an interleukin-13 antagonist, to adolescents aged 12-17 years in the EU. The positive opinion recommends an initial dose of 600 mg administered subcutaneously followed by 300 mg every other week, the dosing recommended for adults.
In December 2021, tralokinumab was approved for adults with moderate to severe AD in the United States, where it is marketed as Adbry. It is also approved for adults in the EU, Great Britain, Canada, the United Arab Emirates, and Switzerland. It is not currently approved for treatment of adolescents in any country, according to the LEO Pharma statement.
A regulatory filing with the U.S. Food and Drug Administration is in progress, the company said, and an additional study of tralokinumab for individuals aged 12 years and older is underway, according to the manufacturer.
The CHMP opinion was supported by data from a phase 3 study (ECZTRA 6) that assessed safety and efficacy of 150-mg or 300-mg doses of tralokinumab, compared with placebo in adolescents with moderate-to-severe AD, the company statement said. The primary outcomes were an Investigator Global Assessment score of clear or almost clear skin (IGA 0/1) and an improvement of at least a 75% on the Eczema Area and Severity Index score (EASI-75). In the study, presented as a poster at a meeting in October 2021, a total of 195 adolescents aged 12-17 with moderate to severe AD who were candidates for systemic therapy were randomly assigned to tralokinumab and 94 to placebo.
At 16 weeks, 21.4% and 17.5% of patients who received 150 mg and 300 mg, respectively, of tralokinumab had IGA scores of 0 or 1, compared with 4.3% of those on placebo (P < .001, P = .002, respectively vs. placebo). In addition, 28.6% and 27.8% of the 150-mg and 300-mg tralokinumab groups, respectively, achieved EASI-75, compared with 6.4% of placebo patients (P < .001, P = .001, respectively, compared with placebo).
Adverse events were similar between the groups, and most were mild or moderate; overall safety profiles were similar to those seen in adult patients.
The European Commission will review the positive opinion and make a final decision.
The research was supported by LEO Pharma.
A version of this article first appeared on Medscape.com.
A White male presented with a 1-month history of recurrent, widespread, painful sores
Coinfection of staphylococci and streptococci can make it more challenging to treat. Lesions typically begin as a vesicle that enlarges and forms an ulcer with a hemorrhagic crust. Even with treatment, the depth of the lesions may result in scarring. Shins and dorsal feet are nearly always involved. Systemic involvement is rare.
Open wounds, bites, or dermatoses are risk factors for the development of ecthyma. Additionally, poor hygiene and malnutrition play a major role in inoculation and severity of the disease. Poor hygiene may serve as the initiating factor for infection, but malnutrition permits further development because of the body’s inability to mount a sufficient immune response. Intravenous drug users and patients with HIV tend to be affected.
When diagnosing ecthyma, it is important to correlate clinical signs with a bacterial culture. This condition can be difficult to treat because of both coinfection and growing antibiotic resistance in staphylococcal and streptococcal species. Specifically, S. aureus has been found to be resistant to beta-lactam antibiotics for many years, with methicillin-resistant S. aureus (MRSA) being first detected in 1961. While a variety of antibiotics are indicated, the prescription should be tailored to cover the cultured organism.
Topical antibiotics are sufficient for more superficial lesions. Both topical and oral antibiotics may be recommended for ecthyma as the infection can spread more deeply into the skin, eventually causing a cellulitis. Treatment protocol for oral agents varies based on which drug is indicated. This patient was seen in the emergency room. His white blood cell count was elevated at 9 × 109/L. He was started empirically on amoxicillin/clavulanate (Augmentin) and ciprofloxacin. Bacterial cultures grew out Streptococcus pyogenes.
The case and photos were submitted by Lucas Shapiro, BS, Nova Southeastern University College of Osteopathic Medicine, Fort Lauderdale, Fla., and Susannah Berke, MD, Three Rivers Dermatology, Coraopolis, Pa. Dr. Bilu Martin edited the column. Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].
References
1. Kwak Y et al. Infect Chemother. 2017 Dec;49(4):301-25.
2. Pereira LB. An Bras Dermatol. 2014 Mar-Apr;89(2):293-9.
3. Wasserzug O et al. Clin Infect Dis. 2009 May 1;48(9):1213-9.
Coinfection of staphylococci and streptococci can make it more challenging to treat. Lesions typically begin as a vesicle that enlarges and forms an ulcer with a hemorrhagic crust. Even with treatment, the depth of the lesions may result in scarring. Shins and dorsal feet are nearly always involved. Systemic involvement is rare.
Open wounds, bites, or dermatoses are risk factors for the development of ecthyma. Additionally, poor hygiene and malnutrition play a major role in inoculation and severity of the disease. Poor hygiene may serve as the initiating factor for infection, but malnutrition permits further development because of the body’s inability to mount a sufficient immune response. Intravenous drug users and patients with HIV tend to be affected.
When diagnosing ecthyma, it is important to correlate clinical signs with a bacterial culture. This condition can be difficult to treat because of both coinfection and growing antibiotic resistance in staphylococcal and streptococcal species. Specifically, S. aureus has been found to be resistant to beta-lactam antibiotics for many years, with methicillin-resistant S. aureus (MRSA) being first detected in 1961. While a variety of antibiotics are indicated, the prescription should be tailored to cover the cultured organism.
Topical antibiotics are sufficient for more superficial lesions. Both topical and oral antibiotics may be recommended for ecthyma as the infection can spread more deeply into the skin, eventually causing a cellulitis. Treatment protocol for oral agents varies based on which drug is indicated. This patient was seen in the emergency room. His white blood cell count was elevated at 9 × 109/L. He was started empirically on amoxicillin/clavulanate (Augmentin) and ciprofloxacin. Bacterial cultures grew out Streptococcus pyogenes.
The case and photos were submitted by Lucas Shapiro, BS, Nova Southeastern University College of Osteopathic Medicine, Fort Lauderdale, Fla., and Susannah Berke, MD, Three Rivers Dermatology, Coraopolis, Pa. Dr. Bilu Martin edited the column. Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].
References
1. Kwak Y et al. Infect Chemother. 2017 Dec;49(4):301-25.
2. Pereira LB. An Bras Dermatol. 2014 Mar-Apr;89(2):293-9.
3. Wasserzug O et al. Clin Infect Dis. 2009 May 1;48(9):1213-9.
Coinfection of staphylococci and streptococci can make it more challenging to treat. Lesions typically begin as a vesicle that enlarges and forms an ulcer with a hemorrhagic crust. Even with treatment, the depth of the lesions may result in scarring. Shins and dorsal feet are nearly always involved. Systemic involvement is rare.
Open wounds, bites, or dermatoses are risk factors for the development of ecthyma. Additionally, poor hygiene and malnutrition play a major role in inoculation and severity of the disease. Poor hygiene may serve as the initiating factor for infection, but malnutrition permits further development because of the body’s inability to mount a sufficient immune response. Intravenous drug users and patients with HIV tend to be affected.
When diagnosing ecthyma, it is important to correlate clinical signs with a bacterial culture. This condition can be difficult to treat because of both coinfection and growing antibiotic resistance in staphylococcal and streptococcal species. Specifically, S. aureus has been found to be resistant to beta-lactam antibiotics for many years, with methicillin-resistant S. aureus (MRSA) being first detected in 1961. While a variety of antibiotics are indicated, the prescription should be tailored to cover the cultured organism.
Topical antibiotics are sufficient for more superficial lesions. Both topical and oral antibiotics may be recommended for ecthyma as the infection can spread more deeply into the skin, eventually causing a cellulitis. Treatment protocol for oral agents varies based on which drug is indicated. This patient was seen in the emergency room. His white blood cell count was elevated at 9 × 109/L. He was started empirically on amoxicillin/clavulanate (Augmentin) and ciprofloxacin. Bacterial cultures grew out Streptococcus pyogenes.
The case and photos were submitted by Lucas Shapiro, BS, Nova Southeastern University College of Osteopathic Medicine, Fort Lauderdale, Fla., and Susannah Berke, MD, Three Rivers Dermatology, Coraopolis, Pa. Dr. Bilu Martin edited the column. Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].
References
1. Kwak Y et al. Infect Chemother. 2017 Dec;49(4):301-25.
2. Pereira LB. An Bras Dermatol. 2014 Mar-Apr;89(2):293-9.
3. Wasserzug O et al. Clin Infect Dis. 2009 May 1;48(9):1213-9.
New science reveals the best way to take a pill
I want to tell you a story about forgetfulness and haste, and how the combination of the two can lead to frightening consequences. A few years ago, I was lying in bed about to turn out the light when I realized I’d forgotten to take “my pill.”
Like some 161 million other American adults, I was then a consumer of a prescription medication. Being conscientious, I got up, retrieved said pill, and tossed it back. Being lazy, I didn’t bother to grab a glass of water to help the thing go down. Instead, I promptly returned to bed, threw a pillow over my head, and prepared for sleep.
Within seconds, I began to feel a burning sensation in my chest. After about a minute, that burn became a crippling pain. Not wanting to alarm my wife, I went into the living room, where I spent the next 30 minutes doubled over in agony. Was I having a heart attack? I phoned my sister, a hospitalist in Texas. She advised me to take myself to the ED to get checked out.
If only I’d known then about “Duke.” He could have told me how critical body posture is when people swallow pills.
Who’s Duke?
Duke is a computer representation of a 34-year-old, anatomically normal human male created by computer scientists at the IT’IS Foundation, a nonprofit group based in Switzerland that works on a variety of projects in health care technology. Using Duke, Rajat Mittal, PhD, a professor of medicine at the Johns Hopkins University, Baltimore, created a computer model called “StomachSim” to explore the process of digestion.
Their research, published in the journal Physics of Fluids, turned up several surprising findings about the dynamics of swallowing pills – the most common way medication is used worldwide.
Dr. Mittal said he chose to study the stomach because the functions of most other organ systems, from the heart to the brain, have already attracted plenty of attention from scientists.
“As I was looking to initiate research in some new directions, the implications of stomach biomechanics on important conditions such as diabetes, obesity, and gastroparesis became apparent to me,” he said. “It was clear that bioengineering research in this arena lags other more ‘sexy’ areas such as cardiovascular flows by at least 20 years, and there seemed to be a great opportunity to do impactful work.”
Your posture may help a pill work better
Several well-known things affect a pill’s ability to disperse its contents into the gut and be used by the body, such as the stomach’s contents (a heavy breakfast, a mix of liquids like juice, milk, and coffee) and the motion of the organ’s walls. But Dr. Mittal’s group learned that Duke’s posture also played a major role.
The researchers ran Duke through computer simulations in varying postures: upright, leaning right, leaning left, and leaning back, while keeping all the other parts of their analyses (like the things mentioned above) the same.
They found that posture determined as much as 83% of how quickly a pill disperses into the intestines. The most efficient position was leaning right. The least was leaning left, which prevented the pill from reaching the antrum, or bottom section of the stomach, and thus kept all but traces of the dissolved drug from entering the duodenum, where the stomach joins the small intestine. (Interestingly, Jews who observe Passover are advised to recline to the left during the meal as a symbol of freedom and leisure.)
That makes sense if you think about the stomach’s shape, which looks kind of like a bean, curving from the left to the right side of the body. Because of gravity, your position will change where the pill lands.
a condition in which the stomach loses the ability to empty properly.
How this could help people
Among the groups most likely to benefit from such studies, Dr. Mittal said, are the elderly – who both take a lot of pills and are more prone to trouble swallowing because of age-related changes in their esophagus – and the bedridden, who can’t easily shift their posture. The findings may also lead to improvements in the ability to treat people with gastroparesis, a particular problem for people with diabetes.
Future studies with Duke and similar simulations will look at how the GI system digests proteins, carbohydrates, and fatty meals, Dr. Mittal said.
In the meantime, Dr. Mittal offered the following advice: “Standing or sitting upright after taking a pill is fine. If you have to take a pill lying down, stay on your back or on your right side. Avoid lying on your left side after taking a pill.”
As for what happened to me, any gastroenterologist reading this has figured out that my condition was not heart-related. Instead, I likely was having a bout of pill esophagitis, irritation that can result from medications that aggravate the mucosa of the food tube. Although painful, esophagitis isn’t life-threatening. After about an hour, the pain began to subside, and by the next morning I was fine, with only a faint ache in my chest to remind me of my earlier torment. (Researchers noted an increase in the condition early in the COVID-19 pandemic, linked to the antibiotic doxycycline.)
And, in the interest of accuracy, my pill problem began above the stomach. Nothing in the Hopkins research suggests that the alignment of the esophagus plays a role in how drugs disperse in the gut – unless, of course, it prevents those pills from reaching the stomach in the first place.
A version of this article first appeared on WebMD.com.
I want to tell you a story about forgetfulness and haste, and how the combination of the two can lead to frightening consequences. A few years ago, I was lying in bed about to turn out the light when I realized I’d forgotten to take “my pill.”
Like some 161 million other American adults, I was then a consumer of a prescription medication. Being conscientious, I got up, retrieved said pill, and tossed it back. Being lazy, I didn’t bother to grab a glass of water to help the thing go down. Instead, I promptly returned to bed, threw a pillow over my head, and prepared for sleep.
Within seconds, I began to feel a burning sensation in my chest. After about a minute, that burn became a crippling pain. Not wanting to alarm my wife, I went into the living room, where I spent the next 30 minutes doubled over in agony. Was I having a heart attack? I phoned my sister, a hospitalist in Texas. She advised me to take myself to the ED to get checked out.
If only I’d known then about “Duke.” He could have told me how critical body posture is when people swallow pills.
Who’s Duke?
Duke is a computer representation of a 34-year-old, anatomically normal human male created by computer scientists at the IT’IS Foundation, a nonprofit group based in Switzerland that works on a variety of projects in health care technology. Using Duke, Rajat Mittal, PhD, a professor of medicine at the Johns Hopkins University, Baltimore, created a computer model called “StomachSim” to explore the process of digestion.
Their research, published in the journal Physics of Fluids, turned up several surprising findings about the dynamics of swallowing pills – the most common way medication is used worldwide.
Dr. Mittal said he chose to study the stomach because the functions of most other organ systems, from the heart to the brain, have already attracted plenty of attention from scientists.
“As I was looking to initiate research in some new directions, the implications of stomach biomechanics on important conditions such as diabetes, obesity, and gastroparesis became apparent to me,” he said. “It was clear that bioengineering research in this arena lags other more ‘sexy’ areas such as cardiovascular flows by at least 20 years, and there seemed to be a great opportunity to do impactful work.”
Your posture may help a pill work better
Several well-known things affect a pill’s ability to disperse its contents into the gut and be used by the body, such as the stomach’s contents (a heavy breakfast, a mix of liquids like juice, milk, and coffee) and the motion of the organ’s walls. But Dr. Mittal’s group learned that Duke’s posture also played a major role.
The researchers ran Duke through computer simulations in varying postures: upright, leaning right, leaning left, and leaning back, while keeping all the other parts of their analyses (like the things mentioned above) the same.
They found that posture determined as much as 83% of how quickly a pill disperses into the intestines. The most efficient position was leaning right. The least was leaning left, which prevented the pill from reaching the antrum, or bottom section of the stomach, and thus kept all but traces of the dissolved drug from entering the duodenum, where the stomach joins the small intestine. (Interestingly, Jews who observe Passover are advised to recline to the left during the meal as a symbol of freedom and leisure.)
That makes sense if you think about the stomach’s shape, which looks kind of like a bean, curving from the left to the right side of the body. Because of gravity, your position will change where the pill lands.
a condition in which the stomach loses the ability to empty properly.
How this could help people
Among the groups most likely to benefit from such studies, Dr. Mittal said, are the elderly – who both take a lot of pills and are more prone to trouble swallowing because of age-related changes in their esophagus – and the bedridden, who can’t easily shift their posture. The findings may also lead to improvements in the ability to treat people with gastroparesis, a particular problem for people with diabetes.
Future studies with Duke and similar simulations will look at how the GI system digests proteins, carbohydrates, and fatty meals, Dr. Mittal said.
In the meantime, Dr. Mittal offered the following advice: “Standing or sitting upright after taking a pill is fine. If you have to take a pill lying down, stay on your back or on your right side. Avoid lying on your left side after taking a pill.”
As for what happened to me, any gastroenterologist reading this has figured out that my condition was not heart-related. Instead, I likely was having a bout of pill esophagitis, irritation that can result from medications that aggravate the mucosa of the food tube. Although painful, esophagitis isn’t life-threatening. After about an hour, the pain began to subside, and by the next morning I was fine, with only a faint ache in my chest to remind me of my earlier torment. (Researchers noted an increase in the condition early in the COVID-19 pandemic, linked to the antibiotic doxycycline.)
And, in the interest of accuracy, my pill problem began above the stomach. Nothing in the Hopkins research suggests that the alignment of the esophagus plays a role in how drugs disperse in the gut – unless, of course, it prevents those pills from reaching the stomach in the first place.
A version of this article first appeared on WebMD.com.
I want to tell you a story about forgetfulness and haste, and how the combination of the two can lead to frightening consequences. A few years ago, I was lying in bed about to turn out the light when I realized I’d forgotten to take “my pill.”
Like some 161 million other American adults, I was then a consumer of a prescription medication. Being conscientious, I got up, retrieved said pill, and tossed it back. Being lazy, I didn’t bother to grab a glass of water to help the thing go down. Instead, I promptly returned to bed, threw a pillow over my head, and prepared for sleep.
Within seconds, I began to feel a burning sensation in my chest. After about a minute, that burn became a crippling pain. Not wanting to alarm my wife, I went into the living room, where I spent the next 30 minutes doubled over in agony. Was I having a heart attack? I phoned my sister, a hospitalist in Texas. She advised me to take myself to the ED to get checked out.
If only I’d known then about “Duke.” He could have told me how critical body posture is when people swallow pills.
Who’s Duke?
Duke is a computer representation of a 34-year-old, anatomically normal human male created by computer scientists at the IT’IS Foundation, a nonprofit group based in Switzerland that works on a variety of projects in health care technology. Using Duke, Rajat Mittal, PhD, a professor of medicine at the Johns Hopkins University, Baltimore, created a computer model called “StomachSim” to explore the process of digestion.
Their research, published in the journal Physics of Fluids, turned up several surprising findings about the dynamics of swallowing pills – the most common way medication is used worldwide.
Dr. Mittal said he chose to study the stomach because the functions of most other organ systems, from the heart to the brain, have already attracted plenty of attention from scientists.
“As I was looking to initiate research in some new directions, the implications of stomach biomechanics on important conditions such as diabetes, obesity, and gastroparesis became apparent to me,” he said. “It was clear that bioengineering research in this arena lags other more ‘sexy’ areas such as cardiovascular flows by at least 20 years, and there seemed to be a great opportunity to do impactful work.”
Your posture may help a pill work better
Several well-known things affect a pill’s ability to disperse its contents into the gut and be used by the body, such as the stomach’s contents (a heavy breakfast, a mix of liquids like juice, milk, and coffee) and the motion of the organ’s walls. But Dr. Mittal’s group learned that Duke’s posture also played a major role.
The researchers ran Duke through computer simulations in varying postures: upright, leaning right, leaning left, and leaning back, while keeping all the other parts of their analyses (like the things mentioned above) the same.
They found that posture determined as much as 83% of how quickly a pill disperses into the intestines. The most efficient position was leaning right. The least was leaning left, which prevented the pill from reaching the antrum, or bottom section of the stomach, and thus kept all but traces of the dissolved drug from entering the duodenum, where the stomach joins the small intestine. (Interestingly, Jews who observe Passover are advised to recline to the left during the meal as a symbol of freedom and leisure.)
That makes sense if you think about the stomach’s shape, which looks kind of like a bean, curving from the left to the right side of the body. Because of gravity, your position will change where the pill lands.
a condition in which the stomach loses the ability to empty properly.
How this could help people
Among the groups most likely to benefit from such studies, Dr. Mittal said, are the elderly – who both take a lot of pills and are more prone to trouble swallowing because of age-related changes in their esophagus – and the bedridden, who can’t easily shift their posture. The findings may also lead to improvements in the ability to treat people with gastroparesis, a particular problem for people with diabetes.
Future studies with Duke and similar simulations will look at how the GI system digests proteins, carbohydrates, and fatty meals, Dr. Mittal said.
In the meantime, Dr. Mittal offered the following advice: “Standing or sitting upright after taking a pill is fine. If you have to take a pill lying down, stay on your back or on your right side. Avoid lying on your left side after taking a pill.”
As for what happened to me, any gastroenterologist reading this has figured out that my condition was not heart-related. Instead, I likely was having a bout of pill esophagitis, irritation that can result from medications that aggravate the mucosa of the food tube. Although painful, esophagitis isn’t life-threatening. After about an hour, the pain began to subside, and by the next morning I was fine, with only a faint ache in my chest to remind me of my earlier torment. (Researchers noted an increase in the condition early in the COVID-19 pandemic, linked to the antibiotic doxycycline.)
And, in the interest of accuracy, my pill problem began above the stomach. Nothing in the Hopkins research suggests that the alignment of the esophagus plays a role in how drugs disperse in the gut – unless, of course, it prevents those pills from reaching the stomach in the first place.
A version of this article first appeared on WebMD.com.
Brodalumab suicide risk similar to other biologics, postmarket study finds
.
The Food and Drug Administration approved brodalumab (Siliq) in 2017 for treatment of moderate to severe plaque psoriasis with a boxed warning for suicidal ideation and behavior and an associated Risk Evaluation and Mitigation Strategies (REMS) program indicating an increased risk of suicidality.
Half a decade later, “the available worldwide data do not support the notion that brodalumab has a unique risk of increased suicides,” senior investigator John Koo, MD, and coinvestigators at the University of California, San Francisco, wrote in a preproof article in JAAD International, noting that postmarketing data are “often considered a better reflection of real-world outcomes than clinical trials.”
The researchers extracted data through the end of 2021 on the number of completed suicides for brodalumab and ten other biologics approved for psoriasis from the FDA’s Adverse Events Reporting System (FAERS), an international publicly available database. The researchers included suicide data on the biologics for all indications.
The authors contacted pharmaceutical companies to determine the total number of patients prescribed each drug, securing mostly “best estimates” data on 5 of the 11 biologics available for psoriasis. The researchers then calculated the number of completed suicides per total number of prescribed patients.
For brodalumab, across 20,871 total prescriptions, there was only one verifiable suicide. It occurred in a Japanese man with terminal cancer and no nearby relatives 36 days after his first dose. The suicide rate for brodalumab was similar to that of ixekizumab, secukinumab, infliximab, and adalimumab.
“Brodalumab is a very efficacious agent and may have the fastest onset of action, yet its usage is minimal compared to the other agents because of this ‘black box’ warning ... despite the fact that it’s the least expensive of any biologic,” Dr. Koo, professor of dermatology and director of the Psoriasis and Skin Treatment Center, University of California, San Francisco, said in an interview.
Dr. Koo, who is board-certified in both dermatology and psychiatry, said he believes the boxed warning was never warranted. All three of the verified completed suicides that occurred during clinical trials of brodalumab for psoriasis were in people who had underlying psychiatric disorders or significant stressors, such as going to jail in one case, and depression and significant isolation in another, he said.
(An analysis of psychiatric adverse events during the psoriasis clinical trials, involving more than 4,000 patients, was published online Oct. 4, 2017, in the Journal of the American Academy of Dermatology.
George Han, MD, PhD, associate professor and director of research and teledermatology at the Zucker School of Medicine at Hofstra/Northwell, New Hyde Park, N.Y., who was not involved in the research, said the new data is reassuring.
“We sometimes put it into context [in thinking and counseling about risk] that in the trials for brodalumab, the number of suicide attempts [versus completed suicides] was not an outlier,” he said. “But it’s hard to know what to make of that, so this piece of knowledge that the postmarketing data show there’s no safety signal should give people a lot of reassurance.”
Dr. Han said he has used the medication, a fully human anti-interleukin 17 receptor A monoclonal antibody, in many patients who “have not done so well on other biologics and it’s been a lifesaver ... a couple who have switched over have maintained the longest level of clearance they’ve had with anything. It’s quite striking.”
The efficacy stems at least partly from its mechanism of blocking all cytokines in the IL-17 family – including those involved in the “feedback loops that perpetuate psoriasis” – rather than just one as other biologics do, Dr. Han said.
Usage of the drug has been hindered by the black box warning and REMS program, not only because of the extra steps required and hesitation potentially evoked, but because samples are not available, and because the “formulary access is not what it could have been otherwise,” he noted.
The Siliq REMS patient enrollment form requires patients to pledge awareness of the fact that suicidal thoughts and behaviors have occurred in treated patients and that they should seek medical attention if they experience suicidal thoughts or new or worsening depression, anxiety, or other mood changes. Prescribers must be certified with the program and must pledge on each enrollment form that they have counseled their patients.
The box warning states that there is no established causal association between treatment with brodalumab and increased risk for suicidal ideation and behaviors (SIB).
Individuals with psoriasis are an “already vulnerable population” who have been shown in reviews and meta-analyses to have a higher prevalence of depression and a higher risk of SIB than those without the disease, Dr. Koo and colleagues wrote in a narrative review published in Cutis .
Regardless of therapy, they wrote in the review, dermatologists should assess for any history of depression and SIB, and evaluate for signs and symptoms of current depression and SIB, referring patients as necessary to primary care or mental health care.
In the psoriasis trials, brodalumab treatment appeared to improve symptoms of depression and anxiety – a finding consistent with the effects reported for other biologic therapies, they wrote.
The first author on the newly published preproof is Samuel Yeroushalmi, BS, a fourth-year medical student at George Washington University, Washington.
Siliq is marketed by Valeant Pharmaceuticals.
Dr. Koo disclosed that he is an adviser/consultant/speaker for numerous pharmaceutical companies, but not those that were involved in the development of brodalumab. Dr. Han said he has relationships with numerous companies, including those that have developed brodalumab and other biologic agents used for psoriasis. The authors declared funding sources as none.
.
The Food and Drug Administration approved brodalumab (Siliq) in 2017 for treatment of moderate to severe plaque psoriasis with a boxed warning for suicidal ideation and behavior and an associated Risk Evaluation and Mitigation Strategies (REMS) program indicating an increased risk of suicidality.
Half a decade later, “the available worldwide data do not support the notion that brodalumab has a unique risk of increased suicides,” senior investigator John Koo, MD, and coinvestigators at the University of California, San Francisco, wrote in a preproof article in JAAD International, noting that postmarketing data are “often considered a better reflection of real-world outcomes than clinical trials.”
The researchers extracted data through the end of 2021 on the number of completed suicides for brodalumab and ten other biologics approved for psoriasis from the FDA’s Adverse Events Reporting System (FAERS), an international publicly available database. The researchers included suicide data on the biologics for all indications.
The authors contacted pharmaceutical companies to determine the total number of patients prescribed each drug, securing mostly “best estimates” data on 5 of the 11 biologics available for psoriasis. The researchers then calculated the number of completed suicides per total number of prescribed patients.
For brodalumab, across 20,871 total prescriptions, there was only one verifiable suicide. It occurred in a Japanese man with terminal cancer and no nearby relatives 36 days after his first dose. The suicide rate for brodalumab was similar to that of ixekizumab, secukinumab, infliximab, and adalimumab.
“Brodalumab is a very efficacious agent and may have the fastest onset of action, yet its usage is minimal compared to the other agents because of this ‘black box’ warning ... despite the fact that it’s the least expensive of any biologic,” Dr. Koo, professor of dermatology and director of the Psoriasis and Skin Treatment Center, University of California, San Francisco, said in an interview.
Dr. Koo, who is board-certified in both dermatology and psychiatry, said he believes the boxed warning was never warranted. All three of the verified completed suicides that occurred during clinical trials of brodalumab for psoriasis were in people who had underlying psychiatric disorders or significant stressors, such as going to jail in one case, and depression and significant isolation in another, he said.
(An analysis of psychiatric adverse events during the psoriasis clinical trials, involving more than 4,000 patients, was published online Oct. 4, 2017, in the Journal of the American Academy of Dermatology.
George Han, MD, PhD, associate professor and director of research and teledermatology at the Zucker School of Medicine at Hofstra/Northwell, New Hyde Park, N.Y., who was not involved in the research, said the new data is reassuring.
“We sometimes put it into context [in thinking and counseling about risk] that in the trials for brodalumab, the number of suicide attempts [versus completed suicides] was not an outlier,” he said. “But it’s hard to know what to make of that, so this piece of knowledge that the postmarketing data show there’s no safety signal should give people a lot of reassurance.”
Dr. Han said he has used the medication, a fully human anti-interleukin 17 receptor A monoclonal antibody, in many patients who “have not done so well on other biologics and it’s been a lifesaver ... a couple who have switched over have maintained the longest level of clearance they’ve had with anything. It’s quite striking.”
The efficacy stems at least partly from its mechanism of blocking all cytokines in the IL-17 family – including those involved in the “feedback loops that perpetuate psoriasis” – rather than just one as other biologics do, Dr. Han said.
Usage of the drug has been hindered by the black box warning and REMS program, not only because of the extra steps required and hesitation potentially evoked, but because samples are not available, and because the “formulary access is not what it could have been otherwise,” he noted.
The Siliq REMS patient enrollment form requires patients to pledge awareness of the fact that suicidal thoughts and behaviors have occurred in treated patients and that they should seek medical attention if they experience suicidal thoughts or new or worsening depression, anxiety, or other mood changes. Prescribers must be certified with the program and must pledge on each enrollment form that they have counseled their patients.
The box warning states that there is no established causal association between treatment with brodalumab and increased risk for suicidal ideation and behaviors (SIB).
Individuals with psoriasis are an “already vulnerable population” who have been shown in reviews and meta-analyses to have a higher prevalence of depression and a higher risk of SIB than those without the disease, Dr. Koo and colleagues wrote in a narrative review published in Cutis .
Regardless of therapy, they wrote in the review, dermatologists should assess for any history of depression and SIB, and evaluate for signs and symptoms of current depression and SIB, referring patients as necessary to primary care or mental health care.
In the psoriasis trials, brodalumab treatment appeared to improve symptoms of depression and anxiety – a finding consistent with the effects reported for other biologic therapies, they wrote.
The first author on the newly published preproof is Samuel Yeroushalmi, BS, a fourth-year medical student at George Washington University, Washington.
Siliq is marketed by Valeant Pharmaceuticals.
Dr. Koo disclosed that he is an adviser/consultant/speaker for numerous pharmaceutical companies, but not those that were involved in the development of brodalumab. Dr. Han said he has relationships with numerous companies, including those that have developed brodalumab and other biologic agents used for psoriasis. The authors declared funding sources as none.
.
The Food and Drug Administration approved brodalumab (Siliq) in 2017 for treatment of moderate to severe plaque psoriasis with a boxed warning for suicidal ideation and behavior and an associated Risk Evaluation and Mitigation Strategies (REMS) program indicating an increased risk of suicidality.
Half a decade later, “the available worldwide data do not support the notion that brodalumab has a unique risk of increased suicides,” senior investigator John Koo, MD, and coinvestigators at the University of California, San Francisco, wrote in a preproof article in JAAD International, noting that postmarketing data are “often considered a better reflection of real-world outcomes than clinical trials.”
The researchers extracted data through the end of 2021 on the number of completed suicides for brodalumab and ten other biologics approved for psoriasis from the FDA’s Adverse Events Reporting System (FAERS), an international publicly available database. The researchers included suicide data on the biologics for all indications.
The authors contacted pharmaceutical companies to determine the total number of patients prescribed each drug, securing mostly “best estimates” data on 5 of the 11 biologics available for psoriasis. The researchers then calculated the number of completed suicides per total number of prescribed patients.
For brodalumab, across 20,871 total prescriptions, there was only one verifiable suicide. It occurred in a Japanese man with terminal cancer and no nearby relatives 36 days after his first dose. The suicide rate for brodalumab was similar to that of ixekizumab, secukinumab, infliximab, and adalimumab.
“Brodalumab is a very efficacious agent and may have the fastest onset of action, yet its usage is minimal compared to the other agents because of this ‘black box’ warning ... despite the fact that it’s the least expensive of any biologic,” Dr. Koo, professor of dermatology and director of the Psoriasis and Skin Treatment Center, University of California, San Francisco, said in an interview.
Dr. Koo, who is board-certified in both dermatology and psychiatry, said he believes the boxed warning was never warranted. All three of the verified completed suicides that occurred during clinical trials of brodalumab for psoriasis were in people who had underlying psychiatric disorders or significant stressors, such as going to jail in one case, and depression and significant isolation in another, he said.
(An analysis of psychiatric adverse events during the psoriasis clinical trials, involving more than 4,000 patients, was published online Oct. 4, 2017, in the Journal of the American Academy of Dermatology.
George Han, MD, PhD, associate professor and director of research and teledermatology at the Zucker School of Medicine at Hofstra/Northwell, New Hyde Park, N.Y., who was not involved in the research, said the new data is reassuring.
“We sometimes put it into context [in thinking and counseling about risk] that in the trials for brodalumab, the number of suicide attempts [versus completed suicides] was not an outlier,” he said. “But it’s hard to know what to make of that, so this piece of knowledge that the postmarketing data show there’s no safety signal should give people a lot of reassurance.”
Dr. Han said he has used the medication, a fully human anti-interleukin 17 receptor A monoclonal antibody, in many patients who “have not done so well on other biologics and it’s been a lifesaver ... a couple who have switched over have maintained the longest level of clearance they’ve had with anything. It’s quite striking.”
The efficacy stems at least partly from its mechanism of blocking all cytokines in the IL-17 family – including those involved in the “feedback loops that perpetuate psoriasis” – rather than just one as other biologics do, Dr. Han said.
Usage of the drug has been hindered by the black box warning and REMS program, not only because of the extra steps required and hesitation potentially evoked, but because samples are not available, and because the “formulary access is not what it could have been otherwise,” he noted.
The Siliq REMS patient enrollment form requires patients to pledge awareness of the fact that suicidal thoughts and behaviors have occurred in treated patients and that they should seek medical attention if they experience suicidal thoughts or new or worsening depression, anxiety, or other mood changes. Prescribers must be certified with the program and must pledge on each enrollment form that they have counseled their patients.
The box warning states that there is no established causal association between treatment with brodalumab and increased risk for suicidal ideation and behaviors (SIB).
Individuals with psoriasis are an “already vulnerable population” who have been shown in reviews and meta-analyses to have a higher prevalence of depression and a higher risk of SIB than those without the disease, Dr. Koo and colleagues wrote in a narrative review published in Cutis .
Regardless of therapy, they wrote in the review, dermatologists should assess for any history of depression and SIB, and evaluate for signs and symptoms of current depression and SIB, referring patients as necessary to primary care or mental health care.
In the psoriasis trials, brodalumab treatment appeared to improve symptoms of depression and anxiety – a finding consistent with the effects reported for other biologic therapies, they wrote.
The first author on the newly published preproof is Samuel Yeroushalmi, BS, a fourth-year medical student at George Washington University, Washington.
Siliq is marketed by Valeant Pharmaceuticals.
Dr. Koo disclosed that he is an adviser/consultant/speaker for numerous pharmaceutical companies, but not those that were involved in the development of brodalumab. Dr. Han said he has relationships with numerous companies, including those that have developed brodalumab and other biologic agents used for psoriasis. The authors declared funding sources as none.
Hope shines bright for hidradenitis suppurativa treatments
in separate trials.
Around 40%-50% of patients exhibited a clinical response to these agents at 16 weeks, a leading HS expert reported at the annual congress of the European Academy of Dermatology and Venereology.
Time in the spotlight for HS
Research into HS is “an incredibly active field at this moment,” said Alexa B. Kimball, MD, MPH, professor of dermatology, Harvard Medical School, and president and chief executive officer of Harvard Medical Faculty Physicians at Beth Israel Deaconess Medical Center, Boston.
It’s “been great for advancing our understanding of the biology and the treatments that we will be able to use,” she said.
During the late-breaking sessions at the annual EADV Congress, Dr. Kimball presented data from two trials – SUNSHINE and SUNRISE – that investigated the efficacy, safety and tolerability of the interleukin (IL) 17A inhibitor secukinumab (Cosentyx) versus placebo in the treatment of moderate to severe HS.
“This is only the second phase 3 program we have ever seen in HS and the first one since 2016,” Dr. Kimball said of the trials. It’s also the largest trial program in HS conducted to date, she added, “so it really is a milestone.”
The last big development was when adalimumab, a tumor necrosis factor (TNF) blocker, gained regulatory approval for HS in 2016, observed Neil Patel, PhD, MRCP, who leads the HS service at Imperial College Healthcare NHS Trust in London.
“Adalimumab has been very helpful for many patients, but not all patients respond, and others may respond initially but then the treatment starts to fail after a year or 2,” Dr. Patel said in an interview with this news organization.
“There is definitely a huge need for alternative medication for this condition, which still has a lack of effective treatment options,” added Dr. Patel, who was not involved in either of the studies.
“One major upside for secukinumab is that its safety profile is generally very good and familiarity in the dermatologic community is already well established,” Christopher Sayed, MD, said in a separate interview.
“This will make most providers very comfortable offering it as a potential treatment option sooner rather than later given that its efficacy has now been demonstrated in phase 3 trials,” added Dr. Sayed, associate professor of dermatology at the University of North Carolina at Chapel Hill.
Two identically designed trials
Altogether, SUNSHINE and SUNRISE enrolled just over 1,000 patients at 219 sites in 33 countries. Both trials were identical in their design: A 4-week run-in phase before a randomized, double-blind treatment phase that tested two dosing regimens of secukinumab (300 mg administered subcutaneously) every 2 or 4 weeks vs. placebo for 16 weeks. The trial continued after this time, with patients in the placebo arm re–randomly assigned to treatment with one of the two secukinumab regimens out to a year.
The primary endpoint was the percentage of patients achieving a Hidradenitis Suppurativa Clinical Response (HiSCR) after 16 weeks of treatment, with key secondary endpoints, which were abscess and inflammatory nodule (AN) count, occurrence of flares, and at least a 30% reduction in Patient’s Global Assessment of Skin Pain assessed using a numeric rating scale (NPRS30).
Secukinumab superior to placebo
The HiSCR is defined as at least a 50% decrease in AN count with no increase in the number of abscesses or in the number of draining fistulas relative to baseline. This was achieved by about 42%-45% of patients who received secukinumab every 2 weeks, about 42%-46% of those who received secukinumab every 4 weeks, and about 31%-33% of those on placebo in both studies.
Of note, fewer patients treated with secukinumab (about 15%-20% among those treated every 2 weeks, and about 15% to 23% among those treated every 4 weeks) than those on placebo (27%-29%) experienced flares, defined as at least a 25% increase in AN count and at least a two-point increase relative to baseline values.
Improvement in HS pain can be a difficult parameter to meet, Dr. Kimball noted. “Pain is such an important feature of this disease as it so debilitating for the patients.” More than one-third (almost 36%-39%) of patients given secukinumab vs. just over a quarter (26.9%) given placebo achieved at least a 30% reduction in NPRS30 ratings, she reported. The difference between active and placebo treatment was significant only when secukinumab was given every 2 weeks, however.
“The placebo rates that we see in these studies are exactly parallel to what we saw in other studies, and other disease states when we had a 50% bar of improvement,” Dr. Kimball said when questioned about these results.
“HS is a highly variable disease; it’s maybe not so much the placebo rate or the scoring system used but maybe the 50% bar set for improvement is too low. It’s likely, as data start to mature and a 75% HiSCR can be calculated, that the placebo rates will drop,” she said.
There were no surprises when it came to the safety of secukinumab, being an old player in a new game, she noted. It was “well tolerated” and tolerability was “consistent with the known safety profile,” Dr. Kimball said, “so we expect it to be a new, safe, and effective add to our armamentarium in treating this disease.”
This research involves “basically borrowing drugs from other areas and trying them in HS to see what effect they may have,” Dr. Patel said, noting that drugs such as adalimumab and secukinumab already had a proven track record in other diseases, such as psoriasis. “These early data for secukinumab definitely are very exciting, but we would need to see real-life results” in patients with HS who are not enrolled in trials to see the benefits, he added.
‘Tipping point’ for HS research
“I think we will look back on this meeting and realize that it was an incredibly important tipping point for the treatment of this incredibly debilitating disease,” Dr. Kimball said.
Elsewhere at the meeting, she had presented findings from a phase 2a study that pitted three different kinase inhibitors with different modes of action against each other and compared them with placebo.
The three agents evaluated are an IL-1 receptor–associated kinase 4 inhibitor known as PF-06650833, a tyrosine kinase 2 (TYK2) JAK1 inhibitor brepocitinib, and the TYK2 inhibitor PF-06826647.
“This technique has been used in oncology,” Dr. Kimball said, noting that the ability to test multiple drugs at the same time “means we can really much more efficiently test two different things at the same time, and also put fewer patients at risk for potential problems if drugs don’t work.”
Positive signs for brepocitinib, not the other kinases tested
The results showed that though brepocitinib worked in HS, the other two novel compounds did not appear to have beneficial effects. Just over half (52%) of the 52 patients treated with brepocitinib achieved an HiSCR at 16 weeks, compared with around one-third of those given placebo, PF-06650833, or PF-06826647.
A similar benefit was seen in terms of reduction in flares for brepocitinib but not the other agents, although there was no difference between them all in terms of NPRS30 pain reduction.
“We’ve been able to test three different modalities. This tells us some things about the pathophysiology for HS, which is a very profoundly intensive inflammatory process,” which, Dr. Kimball said, “may require multiple modalities of action to get it under control.” In addition, these “general modalities seem to safe and well tolerated,” she added.
Take-homes for practice and future research
“While it is disappointing that two of the drugs tested did not clearly demonstrate efficacy, it is very possible that these mechanisms of action may be successful targets in the future as new dosing strategies and drugs targeting these pathways are developed,” Dr. Sayed said.
A case in point, he added, was that “adalimumab did not meet treatment endpoints at a dose of 40 mg every other week, but clearly has made a major impact at 40 mg weekly.”
The bottom line is that “both secukinumab and beprocitinib demonstrated efficacy over placebo and are likely to be helpful for a significant number of patients with HS,” Dr. Sayed said. “Hopefully, we’ll see head-to-head trials and more data regarding proportions of patients with deeper responses using criteria such as HiSCR75 and HiSCR90.”
Moreover, “having a larger number of drugs with a range of mechanisms of action is extraordinarily helpful given how difficult the disease can be to manage. We will hopefully continue to see creative approaches and further successes in the current wave of phase 1, 2, and 3 trials that are already underway.”
The SUNSHINE and SUNRISE studies were funded by Novartis Pharma AG, Basel, Switzerland. The phase 2A study Dr. Kimball presented was sponsored by Pfizer.
Dr. Kimball disclosed ties to both Novartis and Pfizer and acts as a consultant and investigator to AbbVie, Bristol-Myers Squibb, Janssen, Eli Lilly, Novartis, and UCB. She is an investigator for Incyte and AnaptysBio; acts as a consultant to Bayer, Boehringer Ingelheim, Ventyz, Moonlake, Lily, Concert, EvoImmune, Sonoma Bio, and Sanofi; receives fellowship funding from Janssen, and serves on the Board of Directors for Almirall.
Dr. Patel had no conflicts of interest to disclose. Dr. Sayed is the director of the HS Foundation, a nonprofit organization, and has acted as an adviser or consultant to, speaker for, and received research funding from multiple drug companies including AbbVie, ChemoCentryx, Incyte, InflaRx, Novartis, and UCB.
A version of this article first appeared on Medscape.com.
in separate trials.
Around 40%-50% of patients exhibited a clinical response to these agents at 16 weeks, a leading HS expert reported at the annual congress of the European Academy of Dermatology and Venereology.
Time in the spotlight for HS
Research into HS is “an incredibly active field at this moment,” said Alexa B. Kimball, MD, MPH, professor of dermatology, Harvard Medical School, and president and chief executive officer of Harvard Medical Faculty Physicians at Beth Israel Deaconess Medical Center, Boston.
It’s “been great for advancing our understanding of the biology and the treatments that we will be able to use,” she said.
During the late-breaking sessions at the annual EADV Congress, Dr. Kimball presented data from two trials – SUNSHINE and SUNRISE – that investigated the efficacy, safety and tolerability of the interleukin (IL) 17A inhibitor secukinumab (Cosentyx) versus placebo in the treatment of moderate to severe HS.
“This is only the second phase 3 program we have ever seen in HS and the first one since 2016,” Dr. Kimball said of the trials. It’s also the largest trial program in HS conducted to date, she added, “so it really is a milestone.”
The last big development was when adalimumab, a tumor necrosis factor (TNF) blocker, gained regulatory approval for HS in 2016, observed Neil Patel, PhD, MRCP, who leads the HS service at Imperial College Healthcare NHS Trust in London.
“Adalimumab has been very helpful for many patients, but not all patients respond, and others may respond initially but then the treatment starts to fail after a year or 2,” Dr. Patel said in an interview with this news organization.
“There is definitely a huge need for alternative medication for this condition, which still has a lack of effective treatment options,” added Dr. Patel, who was not involved in either of the studies.
“One major upside for secukinumab is that its safety profile is generally very good and familiarity in the dermatologic community is already well established,” Christopher Sayed, MD, said in a separate interview.
“This will make most providers very comfortable offering it as a potential treatment option sooner rather than later given that its efficacy has now been demonstrated in phase 3 trials,” added Dr. Sayed, associate professor of dermatology at the University of North Carolina at Chapel Hill.
Two identically designed trials
Altogether, SUNSHINE and SUNRISE enrolled just over 1,000 patients at 219 sites in 33 countries. Both trials were identical in their design: A 4-week run-in phase before a randomized, double-blind treatment phase that tested two dosing regimens of secukinumab (300 mg administered subcutaneously) every 2 or 4 weeks vs. placebo for 16 weeks. The trial continued after this time, with patients in the placebo arm re–randomly assigned to treatment with one of the two secukinumab regimens out to a year.
The primary endpoint was the percentage of patients achieving a Hidradenitis Suppurativa Clinical Response (HiSCR) after 16 weeks of treatment, with key secondary endpoints, which were abscess and inflammatory nodule (AN) count, occurrence of flares, and at least a 30% reduction in Patient’s Global Assessment of Skin Pain assessed using a numeric rating scale (NPRS30).
Secukinumab superior to placebo
The HiSCR is defined as at least a 50% decrease in AN count with no increase in the number of abscesses or in the number of draining fistulas relative to baseline. This was achieved by about 42%-45% of patients who received secukinumab every 2 weeks, about 42%-46% of those who received secukinumab every 4 weeks, and about 31%-33% of those on placebo in both studies.
Of note, fewer patients treated with secukinumab (about 15%-20% among those treated every 2 weeks, and about 15% to 23% among those treated every 4 weeks) than those on placebo (27%-29%) experienced flares, defined as at least a 25% increase in AN count and at least a two-point increase relative to baseline values.
Improvement in HS pain can be a difficult parameter to meet, Dr. Kimball noted. “Pain is such an important feature of this disease as it so debilitating for the patients.” More than one-third (almost 36%-39%) of patients given secukinumab vs. just over a quarter (26.9%) given placebo achieved at least a 30% reduction in NPRS30 ratings, she reported. The difference between active and placebo treatment was significant only when secukinumab was given every 2 weeks, however.
“The placebo rates that we see in these studies are exactly parallel to what we saw in other studies, and other disease states when we had a 50% bar of improvement,” Dr. Kimball said when questioned about these results.
“HS is a highly variable disease; it’s maybe not so much the placebo rate or the scoring system used but maybe the 50% bar set for improvement is too low. It’s likely, as data start to mature and a 75% HiSCR can be calculated, that the placebo rates will drop,” she said.
There were no surprises when it came to the safety of secukinumab, being an old player in a new game, she noted. It was “well tolerated” and tolerability was “consistent with the known safety profile,” Dr. Kimball said, “so we expect it to be a new, safe, and effective add to our armamentarium in treating this disease.”
This research involves “basically borrowing drugs from other areas and trying them in HS to see what effect they may have,” Dr. Patel said, noting that drugs such as adalimumab and secukinumab already had a proven track record in other diseases, such as psoriasis. “These early data for secukinumab definitely are very exciting, but we would need to see real-life results” in patients with HS who are not enrolled in trials to see the benefits, he added.
‘Tipping point’ for HS research
“I think we will look back on this meeting and realize that it was an incredibly important tipping point for the treatment of this incredibly debilitating disease,” Dr. Kimball said.
Elsewhere at the meeting, she had presented findings from a phase 2a study that pitted three different kinase inhibitors with different modes of action against each other and compared them with placebo.
The three agents evaluated are an IL-1 receptor–associated kinase 4 inhibitor known as PF-06650833, a tyrosine kinase 2 (TYK2) JAK1 inhibitor brepocitinib, and the TYK2 inhibitor PF-06826647.
“This technique has been used in oncology,” Dr. Kimball said, noting that the ability to test multiple drugs at the same time “means we can really much more efficiently test two different things at the same time, and also put fewer patients at risk for potential problems if drugs don’t work.”
Positive signs for brepocitinib, not the other kinases tested
The results showed that though brepocitinib worked in HS, the other two novel compounds did not appear to have beneficial effects. Just over half (52%) of the 52 patients treated with brepocitinib achieved an HiSCR at 16 weeks, compared with around one-third of those given placebo, PF-06650833, or PF-06826647.
A similar benefit was seen in terms of reduction in flares for brepocitinib but not the other agents, although there was no difference between them all in terms of NPRS30 pain reduction.
“We’ve been able to test three different modalities. This tells us some things about the pathophysiology for HS, which is a very profoundly intensive inflammatory process,” which, Dr. Kimball said, “may require multiple modalities of action to get it under control.” In addition, these “general modalities seem to safe and well tolerated,” she added.
Take-homes for practice and future research
“While it is disappointing that two of the drugs tested did not clearly demonstrate efficacy, it is very possible that these mechanisms of action may be successful targets in the future as new dosing strategies and drugs targeting these pathways are developed,” Dr. Sayed said.
A case in point, he added, was that “adalimumab did not meet treatment endpoints at a dose of 40 mg every other week, but clearly has made a major impact at 40 mg weekly.”
The bottom line is that “both secukinumab and beprocitinib demonstrated efficacy over placebo and are likely to be helpful for a significant number of patients with HS,” Dr. Sayed said. “Hopefully, we’ll see head-to-head trials and more data regarding proportions of patients with deeper responses using criteria such as HiSCR75 and HiSCR90.”
Moreover, “having a larger number of drugs with a range of mechanisms of action is extraordinarily helpful given how difficult the disease can be to manage. We will hopefully continue to see creative approaches and further successes in the current wave of phase 1, 2, and 3 trials that are already underway.”
The SUNSHINE and SUNRISE studies were funded by Novartis Pharma AG, Basel, Switzerland. The phase 2A study Dr. Kimball presented was sponsored by Pfizer.
Dr. Kimball disclosed ties to both Novartis and Pfizer and acts as a consultant and investigator to AbbVie, Bristol-Myers Squibb, Janssen, Eli Lilly, Novartis, and UCB. She is an investigator for Incyte and AnaptysBio; acts as a consultant to Bayer, Boehringer Ingelheim, Ventyz, Moonlake, Lily, Concert, EvoImmune, Sonoma Bio, and Sanofi; receives fellowship funding from Janssen, and serves on the Board of Directors for Almirall.
Dr. Patel had no conflicts of interest to disclose. Dr. Sayed is the director of the HS Foundation, a nonprofit organization, and has acted as an adviser or consultant to, speaker for, and received research funding from multiple drug companies including AbbVie, ChemoCentryx, Incyte, InflaRx, Novartis, and UCB.
A version of this article first appeared on Medscape.com.
in separate trials.
Around 40%-50% of patients exhibited a clinical response to these agents at 16 weeks, a leading HS expert reported at the annual congress of the European Academy of Dermatology and Venereology.
Time in the spotlight for HS
Research into HS is “an incredibly active field at this moment,” said Alexa B. Kimball, MD, MPH, professor of dermatology, Harvard Medical School, and president and chief executive officer of Harvard Medical Faculty Physicians at Beth Israel Deaconess Medical Center, Boston.
It’s “been great for advancing our understanding of the biology and the treatments that we will be able to use,” she said.
During the late-breaking sessions at the annual EADV Congress, Dr. Kimball presented data from two trials – SUNSHINE and SUNRISE – that investigated the efficacy, safety and tolerability of the interleukin (IL) 17A inhibitor secukinumab (Cosentyx) versus placebo in the treatment of moderate to severe HS.
“This is only the second phase 3 program we have ever seen in HS and the first one since 2016,” Dr. Kimball said of the trials. It’s also the largest trial program in HS conducted to date, she added, “so it really is a milestone.”
The last big development was when adalimumab, a tumor necrosis factor (TNF) blocker, gained regulatory approval for HS in 2016, observed Neil Patel, PhD, MRCP, who leads the HS service at Imperial College Healthcare NHS Trust in London.
“Adalimumab has been very helpful for many patients, but not all patients respond, and others may respond initially but then the treatment starts to fail after a year or 2,” Dr. Patel said in an interview with this news organization.
“There is definitely a huge need for alternative medication for this condition, which still has a lack of effective treatment options,” added Dr. Patel, who was not involved in either of the studies.
“One major upside for secukinumab is that its safety profile is generally very good and familiarity in the dermatologic community is already well established,” Christopher Sayed, MD, said in a separate interview.
“This will make most providers very comfortable offering it as a potential treatment option sooner rather than later given that its efficacy has now been demonstrated in phase 3 trials,” added Dr. Sayed, associate professor of dermatology at the University of North Carolina at Chapel Hill.
Two identically designed trials
Altogether, SUNSHINE and SUNRISE enrolled just over 1,000 patients at 219 sites in 33 countries. Both trials were identical in their design: A 4-week run-in phase before a randomized, double-blind treatment phase that tested two dosing regimens of secukinumab (300 mg administered subcutaneously) every 2 or 4 weeks vs. placebo for 16 weeks. The trial continued after this time, with patients in the placebo arm re–randomly assigned to treatment with one of the two secukinumab regimens out to a year.
The primary endpoint was the percentage of patients achieving a Hidradenitis Suppurativa Clinical Response (HiSCR) after 16 weeks of treatment, with key secondary endpoints, which were abscess and inflammatory nodule (AN) count, occurrence of flares, and at least a 30% reduction in Patient’s Global Assessment of Skin Pain assessed using a numeric rating scale (NPRS30).
Secukinumab superior to placebo
The HiSCR is defined as at least a 50% decrease in AN count with no increase in the number of abscesses or in the number of draining fistulas relative to baseline. This was achieved by about 42%-45% of patients who received secukinumab every 2 weeks, about 42%-46% of those who received secukinumab every 4 weeks, and about 31%-33% of those on placebo in both studies.
Of note, fewer patients treated with secukinumab (about 15%-20% among those treated every 2 weeks, and about 15% to 23% among those treated every 4 weeks) than those on placebo (27%-29%) experienced flares, defined as at least a 25% increase in AN count and at least a two-point increase relative to baseline values.
Improvement in HS pain can be a difficult parameter to meet, Dr. Kimball noted. “Pain is such an important feature of this disease as it so debilitating for the patients.” More than one-third (almost 36%-39%) of patients given secukinumab vs. just over a quarter (26.9%) given placebo achieved at least a 30% reduction in NPRS30 ratings, she reported. The difference between active and placebo treatment was significant only when secukinumab was given every 2 weeks, however.
“The placebo rates that we see in these studies are exactly parallel to what we saw in other studies, and other disease states when we had a 50% bar of improvement,” Dr. Kimball said when questioned about these results.
“HS is a highly variable disease; it’s maybe not so much the placebo rate or the scoring system used but maybe the 50% bar set for improvement is too low. It’s likely, as data start to mature and a 75% HiSCR can be calculated, that the placebo rates will drop,” she said.
There were no surprises when it came to the safety of secukinumab, being an old player in a new game, she noted. It was “well tolerated” and tolerability was “consistent with the known safety profile,” Dr. Kimball said, “so we expect it to be a new, safe, and effective add to our armamentarium in treating this disease.”
This research involves “basically borrowing drugs from other areas and trying them in HS to see what effect they may have,” Dr. Patel said, noting that drugs such as adalimumab and secukinumab already had a proven track record in other diseases, such as psoriasis. “These early data for secukinumab definitely are very exciting, but we would need to see real-life results” in patients with HS who are not enrolled in trials to see the benefits, he added.
‘Tipping point’ for HS research
“I think we will look back on this meeting and realize that it was an incredibly important tipping point for the treatment of this incredibly debilitating disease,” Dr. Kimball said.
Elsewhere at the meeting, she had presented findings from a phase 2a study that pitted three different kinase inhibitors with different modes of action against each other and compared them with placebo.
The three agents evaluated are an IL-1 receptor–associated kinase 4 inhibitor known as PF-06650833, a tyrosine kinase 2 (TYK2) JAK1 inhibitor brepocitinib, and the TYK2 inhibitor PF-06826647.
“This technique has been used in oncology,” Dr. Kimball said, noting that the ability to test multiple drugs at the same time “means we can really much more efficiently test two different things at the same time, and also put fewer patients at risk for potential problems if drugs don’t work.”
Positive signs for brepocitinib, not the other kinases tested
The results showed that though brepocitinib worked in HS, the other two novel compounds did not appear to have beneficial effects. Just over half (52%) of the 52 patients treated with brepocitinib achieved an HiSCR at 16 weeks, compared with around one-third of those given placebo, PF-06650833, or PF-06826647.
A similar benefit was seen in terms of reduction in flares for brepocitinib but not the other agents, although there was no difference between them all in terms of NPRS30 pain reduction.
“We’ve been able to test three different modalities. This tells us some things about the pathophysiology for HS, which is a very profoundly intensive inflammatory process,” which, Dr. Kimball said, “may require multiple modalities of action to get it under control.” In addition, these “general modalities seem to safe and well tolerated,” she added.
Take-homes for practice and future research
“While it is disappointing that two of the drugs tested did not clearly demonstrate efficacy, it is very possible that these mechanisms of action may be successful targets in the future as new dosing strategies and drugs targeting these pathways are developed,” Dr. Sayed said.
A case in point, he added, was that “adalimumab did not meet treatment endpoints at a dose of 40 mg every other week, but clearly has made a major impact at 40 mg weekly.”
The bottom line is that “both secukinumab and beprocitinib demonstrated efficacy over placebo and are likely to be helpful for a significant number of patients with HS,” Dr. Sayed said. “Hopefully, we’ll see head-to-head trials and more data regarding proportions of patients with deeper responses using criteria such as HiSCR75 and HiSCR90.”
Moreover, “having a larger number of drugs with a range of mechanisms of action is extraordinarily helpful given how difficult the disease can be to manage. We will hopefully continue to see creative approaches and further successes in the current wave of phase 1, 2, and 3 trials that are already underway.”
The SUNSHINE and SUNRISE studies were funded by Novartis Pharma AG, Basel, Switzerland. The phase 2A study Dr. Kimball presented was sponsored by Pfizer.
Dr. Kimball disclosed ties to both Novartis and Pfizer and acts as a consultant and investigator to AbbVie, Bristol-Myers Squibb, Janssen, Eli Lilly, Novartis, and UCB. She is an investigator for Incyte and AnaptysBio; acts as a consultant to Bayer, Boehringer Ingelheim, Ventyz, Moonlake, Lily, Concert, EvoImmune, Sonoma Bio, and Sanofi; receives fellowship funding from Janssen, and serves on the Board of Directors for Almirall.
Dr. Patel had no conflicts of interest to disclose. Dr. Sayed is the director of the HS Foundation, a nonprofit organization, and has acted as an adviser or consultant to, speaker for, and received research funding from multiple drug companies including AbbVie, ChemoCentryx, Incyte, InflaRx, Novartis, and UCB.
A version of this article first appeared on Medscape.com.
FROM THE EADV CONGRESS
Pandemic has helped clinicians to gain better insight on pernio, expert says
PORTLAND, ORE. – while others are not, according to Lindy P. Fox, MD, professor of dermatology and director of the hospital consultation service at the University of California, San Francisco.
“We’re learning a lot about pernio because of COVID,” Dr. Fox, a member of the American Academy of Dermatology’s Ad Hoc Task Force on COVID-19, said at the annual meeting of the Pacific Dermatologic Association. “Patients with pernio tend to either have bright red or purple individual lesions or an erythromelalgia-like presentation, often waking up in the middle of the night saying ‘my feet hurt. I can’t put sheets over my feet.’ In my experience, the patients with an erythromelalgia-like presentation tend to be a lot harder to treat.”
Establishing terminology to describe pernio-like lesions was a challenge in the early stages of the COVID-19 pandemic, Dr. Fox added, with clinicians using terms like erythema multiforme-like, coxsackie-like, or even necrotic to describe the lesions. “I don’t think pernio is truly necrotic; I think it’s really inflammatory and purpuric,” she said.
Early in the pandemic, studies suggesting a link with these cases and COVID-19 infection include a case series of 318 patients with pernio-like skin lesions who had confirmed or suspected COVID-19. Most of these patients were generally young and healthy and most had relatively mild COVID-19; 7% were laboratory-confirmed COVID-19 positive, and 6% were close contacts of patients with confirmed COVID-19. Pernio-like lesions were the only symptoms in 55% of the patients.
In another study, researchers in France evaluated the clinical, laboratory, and pathologic characteristics of 40 patients who developed chilblain-like lesions (mostly involving the toes) during the COVID-19 pandemic and were seen as outpatients in April 2020 . All were polymerase chain reaction (PCR) negative, 30% were SARS-CoV-2 serology positive, and 60% had elevated D-dimers. Histology obtained from 19 of the patients revealed lymphocytic inflammation and vascular damage, and 8 had IgA positivity.
In a retrospective analysis of seven pediatric chilblains cases during the pandemic, researchers examined the skin biopsies to evaluate histopathological features and explored the presence of SARS-CoV-2 in the tissue. All patients were PCR negative. The authors observed cytoplasmic granular positivity for SARS-CoV-2 spike protein in endothelial cells, a feature that they said showed coronavirus-like particles, consistent with SARS-CoV-2.
Not all studies in the medical literature have demonstrated an association between pernio-like/chilblains-like lesions and COVID-19, though. An analysis of 23 patients, with skin eruptions considered associated with SARS-CoV-2 infections (including 21 cases of chilblains) during the first wave of the pandemic found that the antibody and T-cell response in patients with pandemic chilblains was the same as in negative controls.
“What’s remarkably interesting about this study is that they did autopsies of samples from patients who had died prepandemic, so there was no such thing as COVID-19,” said Dr. Fox, who was not involved with the study. “They stained for viral particles in those patients, and they were positive in a subset of patients. This makes me wonder about what the significance of that staining positivity is.”
Yet another group of investigators looked at what was happening with pernio during the waves of COVID in a study of chilblains cases in children in Spain, and found a stronger association between lockdown and cold temperature, which argues against a direct association between pernio and COVID infection.
In Dr. Fox’s experience, COVID toes can recur, especially upon exposure to cold. “What taught me this in real life is a patient who I saw remotely by video,” she recalled. “It was early on in the pandemic. I could not prove he had COVID no matter how hard I tried, but I do think he had COVID toes at that time.” When he later was confirmed to have COVID, “he got pernio in the same exact location as his original suspected COVID toes.”
According to an analysis of long COVID in the skin, based on cases reported to the American Academy of Dermatology–International League of Dermatological Societies registry from April 8 to Oct. 8, 2020, pernio-like lesions lasted a median of 12 days in patients with lab-confirmed COVID-19 and a median of 15 days in those with suspected COVID-19. But almost 7% of the 103 pernio cases were long-haulers, defined as those with dermatologic signs of COVID that lasted beyond 60 days.
“There are some patients who are resistant to treatment,” Dr. Fox said. “In addition, recurrent lesions make me think that maybe all pernio is triggered by some viral cause. This causes an immunologic phenomenon that’s responding to a viral trigger you’re trying to deal with. That may be the better way to think about COVID toes.”
Different variants of COVID also appear to be changing the characteristics of dermatologic manifestations associated with infection. Results from a large retrospective analysis of nearly 350,000 users of a COVID study App in the United Kingdom found that skin lesions were more predictive of a positive test in the Delta wave, compared with the Omicron wave, while pernio-like lesions were predictive of infection in the Delta wave but not in the Omicron wave.
“And, whether you were vaccinated or unvaccinated really did not influence whether or not you were going to have a skin rash as a presenting sign of COVID, except for the burning rash, which was less in vaccinated patients,” said Dr. Fox, who was not involved with the study.
Dr. Fox reported having no relevant disclosures.
PORTLAND, ORE. – while others are not, according to Lindy P. Fox, MD, professor of dermatology and director of the hospital consultation service at the University of California, San Francisco.
“We’re learning a lot about pernio because of COVID,” Dr. Fox, a member of the American Academy of Dermatology’s Ad Hoc Task Force on COVID-19, said at the annual meeting of the Pacific Dermatologic Association. “Patients with pernio tend to either have bright red or purple individual lesions or an erythromelalgia-like presentation, often waking up in the middle of the night saying ‘my feet hurt. I can’t put sheets over my feet.’ In my experience, the patients with an erythromelalgia-like presentation tend to be a lot harder to treat.”
Establishing terminology to describe pernio-like lesions was a challenge in the early stages of the COVID-19 pandemic, Dr. Fox added, with clinicians using terms like erythema multiforme-like, coxsackie-like, or even necrotic to describe the lesions. “I don’t think pernio is truly necrotic; I think it’s really inflammatory and purpuric,” she said.
Early in the pandemic, studies suggesting a link with these cases and COVID-19 infection include a case series of 318 patients with pernio-like skin lesions who had confirmed or suspected COVID-19. Most of these patients were generally young and healthy and most had relatively mild COVID-19; 7% were laboratory-confirmed COVID-19 positive, and 6% were close contacts of patients with confirmed COVID-19. Pernio-like lesions were the only symptoms in 55% of the patients.
In another study, researchers in France evaluated the clinical, laboratory, and pathologic characteristics of 40 patients who developed chilblain-like lesions (mostly involving the toes) during the COVID-19 pandemic and were seen as outpatients in April 2020 . All were polymerase chain reaction (PCR) negative, 30% were SARS-CoV-2 serology positive, and 60% had elevated D-dimers. Histology obtained from 19 of the patients revealed lymphocytic inflammation and vascular damage, and 8 had IgA positivity.
In a retrospective analysis of seven pediatric chilblains cases during the pandemic, researchers examined the skin biopsies to evaluate histopathological features and explored the presence of SARS-CoV-2 in the tissue. All patients were PCR negative. The authors observed cytoplasmic granular positivity for SARS-CoV-2 spike protein in endothelial cells, a feature that they said showed coronavirus-like particles, consistent with SARS-CoV-2.
Not all studies in the medical literature have demonstrated an association between pernio-like/chilblains-like lesions and COVID-19, though. An analysis of 23 patients, with skin eruptions considered associated with SARS-CoV-2 infections (including 21 cases of chilblains) during the first wave of the pandemic found that the antibody and T-cell response in patients with pandemic chilblains was the same as in negative controls.
“What’s remarkably interesting about this study is that they did autopsies of samples from patients who had died prepandemic, so there was no such thing as COVID-19,” said Dr. Fox, who was not involved with the study. “They stained for viral particles in those patients, and they were positive in a subset of patients. This makes me wonder about what the significance of that staining positivity is.”
Yet another group of investigators looked at what was happening with pernio during the waves of COVID in a study of chilblains cases in children in Spain, and found a stronger association between lockdown and cold temperature, which argues against a direct association between pernio and COVID infection.
In Dr. Fox’s experience, COVID toes can recur, especially upon exposure to cold. “What taught me this in real life is a patient who I saw remotely by video,” she recalled. “It was early on in the pandemic. I could not prove he had COVID no matter how hard I tried, but I do think he had COVID toes at that time.” When he later was confirmed to have COVID, “he got pernio in the same exact location as his original suspected COVID toes.”
According to an analysis of long COVID in the skin, based on cases reported to the American Academy of Dermatology–International League of Dermatological Societies registry from April 8 to Oct. 8, 2020, pernio-like lesions lasted a median of 12 days in patients with lab-confirmed COVID-19 and a median of 15 days in those with suspected COVID-19. But almost 7% of the 103 pernio cases were long-haulers, defined as those with dermatologic signs of COVID that lasted beyond 60 days.
“There are some patients who are resistant to treatment,” Dr. Fox said. “In addition, recurrent lesions make me think that maybe all pernio is triggered by some viral cause. This causes an immunologic phenomenon that’s responding to a viral trigger you’re trying to deal with. That may be the better way to think about COVID toes.”
Different variants of COVID also appear to be changing the characteristics of dermatologic manifestations associated with infection. Results from a large retrospective analysis of nearly 350,000 users of a COVID study App in the United Kingdom found that skin lesions were more predictive of a positive test in the Delta wave, compared with the Omicron wave, while pernio-like lesions were predictive of infection in the Delta wave but not in the Omicron wave.
“And, whether you were vaccinated or unvaccinated really did not influence whether or not you were going to have a skin rash as a presenting sign of COVID, except for the burning rash, which was less in vaccinated patients,” said Dr. Fox, who was not involved with the study.
Dr. Fox reported having no relevant disclosures.
PORTLAND, ORE. – while others are not, according to Lindy P. Fox, MD, professor of dermatology and director of the hospital consultation service at the University of California, San Francisco.
“We’re learning a lot about pernio because of COVID,” Dr. Fox, a member of the American Academy of Dermatology’s Ad Hoc Task Force on COVID-19, said at the annual meeting of the Pacific Dermatologic Association. “Patients with pernio tend to either have bright red or purple individual lesions or an erythromelalgia-like presentation, often waking up in the middle of the night saying ‘my feet hurt. I can’t put sheets over my feet.’ In my experience, the patients with an erythromelalgia-like presentation tend to be a lot harder to treat.”
Establishing terminology to describe pernio-like lesions was a challenge in the early stages of the COVID-19 pandemic, Dr. Fox added, with clinicians using terms like erythema multiforme-like, coxsackie-like, or even necrotic to describe the lesions. “I don’t think pernio is truly necrotic; I think it’s really inflammatory and purpuric,” she said.
Early in the pandemic, studies suggesting a link with these cases and COVID-19 infection include a case series of 318 patients with pernio-like skin lesions who had confirmed or suspected COVID-19. Most of these patients were generally young and healthy and most had relatively mild COVID-19; 7% were laboratory-confirmed COVID-19 positive, and 6% were close contacts of patients with confirmed COVID-19. Pernio-like lesions were the only symptoms in 55% of the patients.
In another study, researchers in France evaluated the clinical, laboratory, and pathologic characteristics of 40 patients who developed chilblain-like lesions (mostly involving the toes) during the COVID-19 pandemic and were seen as outpatients in April 2020 . All were polymerase chain reaction (PCR) negative, 30% were SARS-CoV-2 serology positive, and 60% had elevated D-dimers. Histology obtained from 19 of the patients revealed lymphocytic inflammation and vascular damage, and 8 had IgA positivity.
In a retrospective analysis of seven pediatric chilblains cases during the pandemic, researchers examined the skin biopsies to evaluate histopathological features and explored the presence of SARS-CoV-2 in the tissue. All patients were PCR negative. The authors observed cytoplasmic granular positivity for SARS-CoV-2 spike protein in endothelial cells, a feature that they said showed coronavirus-like particles, consistent with SARS-CoV-2.
Not all studies in the medical literature have demonstrated an association between pernio-like/chilblains-like lesions and COVID-19, though. An analysis of 23 patients, with skin eruptions considered associated with SARS-CoV-2 infections (including 21 cases of chilblains) during the first wave of the pandemic found that the antibody and T-cell response in patients with pandemic chilblains was the same as in negative controls.
“What’s remarkably interesting about this study is that they did autopsies of samples from patients who had died prepandemic, so there was no such thing as COVID-19,” said Dr. Fox, who was not involved with the study. “They stained for viral particles in those patients, and they were positive in a subset of patients. This makes me wonder about what the significance of that staining positivity is.”
Yet another group of investigators looked at what was happening with pernio during the waves of COVID in a study of chilblains cases in children in Spain, and found a stronger association between lockdown and cold temperature, which argues against a direct association between pernio and COVID infection.
In Dr. Fox’s experience, COVID toes can recur, especially upon exposure to cold. “What taught me this in real life is a patient who I saw remotely by video,” she recalled. “It was early on in the pandemic. I could not prove he had COVID no matter how hard I tried, but I do think he had COVID toes at that time.” When he later was confirmed to have COVID, “he got pernio in the same exact location as his original suspected COVID toes.”
According to an analysis of long COVID in the skin, based on cases reported to the American Academy of Dermatology–International League of Dermatological Societies registry from April 8 to Oct. 8, 2020, pernio-like lesions lasted a median of 12 days in patients with lab-confirmed COVID-19 and a median of 15 days in those with suspected COVID-19. But almost 7% of the 103 pernio cases were long-haulers, defined as those with dermatologic signs of COVID that lasted beyond 60 days.
“There are some patients who are resistant to treatment,” Dr. Fox said. “In addition, recurrent lesions make me think that maybe all pernio is triggered by some viral cause. This causes an immunologic phenomenon that’s responding to a viral trigger you’re trying to deal with. That may be the better way to think about COVID toes.”
Different variants of COVID also appear to be changing the characteristics of dermatologic manifestations associated with infection. Results from a large retrospective analysis of nearly 350,000 users of a COVID study App in the United Kingdom found that skin lesions were more predictive of a positive test in the Delta wave, compared with the Omicron wave, while pernio-like lesions were predictive of infection in the Delta wave but not in the Omicron wave.
“And, whether you were vaccinated or unvaccinated really did not influence whether or not you were going to have a skin rash as a presenting sign of COVID, except for the burning rash, which was less in vaccinated patients,” said Dr. Fox, who was not involved with the study.
Dr. Fox reported having no relevant disclosures.
AT PDA 2022
Hidradenitis suppurativa
THE COMPARISON
Severe longstanding hidradenitis suppurativa (Hurley stage III) with architectural changes, ropy scarring, granulation tissue, and purulent discharge in the axilla of
A A 35-year-old Black man.
B A 42-year-old Hispanic woman with a light skin tone.
Hidradenitis suppurativa (HS) is a chronic inflammatory condition of the follicular epithelium that most commonly is found in the axillae and buttocks, as well as the inguinal, perianal, and submammary areas. It is characterized by firm and tender chronic nodules, abscesses complicated by sinus tracts, fistulae, and scarring thought to be related to follicular occlusion. Double-open comedones also may be seen.
The Hurley staging system is widely used to characterize the extent of disease in patients with HS:
- Stage I (mild): nodule(s) and abscess(es) without sinus tracts (tunnels) or scarring;
- Stage II (moderate): recurrent nodule(s) and abscess(es) with a limited number of sinus tracts and/or scarring; and
- Stage III (severe): multiple or extensive sinus tracts, abscesses, and/or scarring across the entire area.
Epidemiology
HS is most common in adults and African American patients. It has a prevalence of 1.3% in African Americans.1 When it occurs in children, it generally develops after the onset of puberty. The incidence is higher in females as well as individuals with a history of smoking and obesity (a higher body mass index).2-5
Key clinical features in people with darker skin tones
The erythema associated with HS may be difficult to see in darker skin tones, but violaceous, dark brown, and gray lesions may be present. When active HS lesions subside, intense hyperpigmentation may be left behind, and in some skin tones a pink or violaceous lesion may be apparent.
Worth noting
HS is disfiguring and has a negative impact on quality of life, including social relationships. Mental health support and screening tools are useful. Pain also is a common concern and may warrant referral to a pain specialist.6 In early disease, HS lesions can be misdiagnosed as an infection that recurs in the same location.
Treatments for HS include oral antibiotics (ie, tetracyclines, rifampin, clindamycin), topical antibiotics, immunosuppressing biologics, metformin, and spironolactone.7 Surgical interventions may be considered earlier in HS management and vary based on the location and severity of the lesions.8
Patients with HS are at risk for developing squamous cell carcinoma in scars, even many years later9; therefore, patients should perform skin checks and be referred to a dermatologist. Squamous cell carcinoma is most commonly found on the buttocks of men with HS and has a poor prognosis.
Health disparity highlight
Although those of African American and African descent have the highest rates of HS,1 the clinical trials for adalimumab (the only biologic approved for HS) enrolled a low number of Black patients.
Thirty HS comorbidities have been identified. Garg et al10 recommended that dermatologists perform examinations for comorbid conditions involving the skin and conduct a simple review of systems for extracutaneous comorbidities. Access to medical care is essential, and health care system barriers affect the ability of some patients to receive adequate continuity of care.
The diagnosis of HS often is delayed due to a lack of knowledge about the condition in the medical community at large and delayed presentation to a dermatologist.
1. Sachdeva M, Shah M, Alavi A. Race-specific prevalence of hidradenitis suppurativa. J Cutan Med Surg. 2021;25:177-187. doi:10.1177/1203475420972348
2. Zouboulis CC, Goyal M, Byrd AS. Hidradenitis suppurativa in skin of colour. Exp Dermatol. 2021;30(suppl 1):27-30. doi:10.1111 /exd.14341
3. Shalom G, Cohen AD. The epidemiology of hidradenitis suppurativa: what do we know? Br J Dermatol. 2019;180:712-713.
4. Theut Riis P, Pedersen OB, Sigsgaard V, et al. Prevalence of patients with self-reported hidradenitis suppurativa in a cohort of Danish blood donors: a cross-sectional study. Br J Dermatol. 2019;180:774-781.
5. Jemec GB, Kimball AB. Hidradenitis suppurativa: epidemiology and scope of the problem. J Am Acad Dermatol. 2015;73(5 suppl 1):S4-S7.
6. Savage KT, Singh V, Patel ZS, et al. Pain management in hidradenitis suppurativa and a proposed treatment algorithm. J Am Acad Dermatol. 2021;85:187-199. doi:10.1016/j.jaad.2020.09.039
7. Alikhan A, Sayed C, Alavi A, et al. North American clinical management guidelines for hidradenitis suppurativa: a publication from the United States and Canadian Hidradenitis Suppurativa Foundations: part II: topical, intralesional, and systemic medical management. J Am Acad Dermatol. 2019;81:91-101.
8. Vellaichamy G, Braunberger TL, Nahhas AF, et al. Surgical procedures for hidradenitis suppurativa. Cutis. 2018;102:13-16.
9. Jung JM, Lee KH, Kim Y-J, et al. Assessment of overall and specific cancer risks in patients with hidradenitis suppurativa. JAMA Dermatol. 2020;156:844-853.
10. Garg A, Malviya N, Strunk A, et al. Comorbidity screening in hidradenitis suppurativa: evidence-based recommendations from the US and Canadian Hidradenitis Suppurativa Foundations. J Am Acad Dermatol. 2022;86:1092-1101. doi:10.1016/ j.jaad.2021.01.059
THE COMPARISON
Severe longstanding hidradenitis suppurativa (Hurley stage III) with architectural changes, ropy scarring, granulation tissue, and purulent discharge in the axilla of
A A 35-year-old Black man.
B A 42-year-old Hispanic woman with a light skin tone.
Hidradenitis suppurativa (HS) is a chronic inflammatory condition of the follicular epithelium that most commonly is found in the axillae and buttocks, as well as the inguinal, perianal, and submammary areas. It is characterized by firm and tender chronic nodules, abscesses complicated by sinus tracts, fistulae, and scarring thought to be related to follicular occlusion. Double-open comedones also may be seen.
The Hurley staging system is widely used to characterize the extent of disease in patients with HS:
- Stage I (mild): nodule(s) and abscess(es) without sinus tracts (tunnels) or scarring;
- Stage II (moderate): recurrent nodule(s) and abscess(es) with a limited number of sinus tracts and/or scarring; and
- Stage III (severe): multiple or extensive sinus tracts, abscesses, and/or scarring across the entire area.
Epidemiology
HS is most common in adults and African American patients. It has a prevalence of 1.3% in African Americans.1 When it occurs in children, it generally develops after the onset of puberty. The incidence is higher in females as well as individuals with a history of smoking and obesity (a higher body mass index).2-5
Key clinical features in people with darker skin tones
The erythema associated with HS may be difficult to see in darker skin tones, but violaceous, dark brown, and gray lesions may be present. When active HS lesions subside, intense hyperpigmentation may be left behind, and in some skin tones a pink or violaceous lesion may be apparent.
Worth noting
HS is disfiguring and has a negative impact on quality of life, including social relationships. Mental health support and screening tools are useful. Pain also is a common concern and may warrant referral to a pain specialist.6 In early disease, HS lesions can be misdiagnosed as an infection that recurs in the same location.
Treatments for HS include oral antibiotics (ie, tetracyclines, rifampin, clindamycin), topical antibiotics, immunosuppressing biologics, metformin, and spironolactone.7 Surgical interventions may be considered earlier in HS management and vary based on the location and severity of the lesions.8
Patients with HS are at risk for developing squamous cell carcinoma in scars, even many years later9; therefore, patients should perform skin checks and be referred to a dermatologist. Squamous cell carcinoma is most commonly found on the buttocks of men with HS and has a poor prognosis.
Health disparity highlight
Although those of African American and African descent have the highest rates of HS,1 the clinical trials for adalimumab (the only biologic approved for HS) enrolled a low number of Black patients.
Thirty HS comorbidities have been identified. Garg et al10 recommended that dermatologists perform examinations for comorbid conditions involving the skin and conduct a simple review of systems for extracutaneous comorbidities. Access to medical care is essential, and health care system barriers affect the ability of some patients to receive adequate continuity of care.
The diagnosis of HS often is delayed due to a lack of knowledge about the condition in the medical community at large and delayed presentation to a dermatologist.
THE COMPARISON
Severe longstanding hidradenitis suppurativa (Hurley stage III) with architectural changes, ropy scarring, granulation tissue, and purulent discharge in the axilla of
A A 35-year-old Black man.
B A 42-year-old Hispanic woman with a light skin tone.
Hidradenitis suppurativa (HS) is a chronic inflammatory condition of the follicular epithelium that most commonly is found in the axillae and buttocks, as well as the inguinal, perianal, and submammary areas. It is characterized by firm and tender chronic nodules, abscesses complicated by sinus tracts, fistulae, and scarring thought to be related to follicular occlusion. Double-open comedones also may be seen.
The Hurley staging system is widely used to characterize the extent of disease in patients with HS:
- Stage I (mild): nodule(s) and abscess(es) without sinus tracts (tunnels) or scarring;
- Stage II (moderate): recurrent nodule(s) and abscess(es) with a limited number of sinus tracts and/or scarring; and
- Stage III (severe): multiple or extensive sinus tracts, abscesses, and/or scarring across the entire area.
Epidemiology
HS is most common in adults and African American patients. It has a prevalence of 1.3% in African Americans.1 When it occurs in children, it generally develops after the onset of puberty. The incidence is higher in females as well as individuals with a history of smoking and obesity (a higher body mass index).2-5
Key clinical features in people with darker skin tones
The erythema associated with HS may be difficult to see in darker skin tones, but violaceous, dark brown, and gray lesions may be present. When active HS lesions subside, intense hyperpigmentation may be left behind, and in some skin tones a pink or violaceous lesion may be apparent.
Worth noting
HS is disfiguring and has a negative impact on quality of life, including social relationships. Mental health support and screening tools are useful. Pain also is a common concern and may warrant referral to a pain specialist.6 In early disease, HS lesions can be misdiagnosed as an infection that recurs in the same location.
Treatments for HS include oral antibiotics (ie, tetracyclines, rifampin, clindamycin), topical antibiotics, immunosuppressing biologics, metformin, and spironolactone.7 Surgical interventions may be considered earlier in HS management and vary based on the location and severity of the lesions.8
Patients with HS are at risk for developing squamous cell carcinoma in scars, even many years later9; therefore, patients should perform skin checks and be referred to a dermatologist. Squamous cell carcinoma is most commonly found on the buttocks of men with HS and has a poor prognosis.
Health disparity highlight
Although those of African American and African descent have the highest rates of HS,1 the clinical trials for adalimumab (the only biologic approved for HS) enrolled a low number of Black patients.
Thirty HS comorbidities have been identified. Garg et al10 recommended that dermatologists perform examinations for comorbid conditions involving the skin and conduct a simple review of systems for extracutaneous comorbidities. Access to medical care is essential, and health care system barriers affect the ability of some patients to receive adequate continuity of care.
The diagnosis of HS often is delayed due to a lack of knowledge about the condition in the medical community at large and delayed presentation to a dermatologist.
1. Sachdeva M, Shah M, Alavi A. Race-specific prevalence of hidradenitis suppurativa. J Cutan Med Surg. 2021;25:177-187. doi:10.1177/1203475420972348
2. Zouboulis CC, Goyal M, Byrd AS. Hidradenitis suppurativa in skin of colour. Exp Dermatol. 2021;30(suppl 1):27-30. doi:10.1111 /exd.14341
3. Shalom G, Cohen AD. The epidemiology of hidradenitis suppurativa: what do we know? Br J Dermatol. 2019;180:712-713.
4. Theut Riis P, Pedersen OB, Sigsgaard V, et al. Prevalence of patients with self-reported hidradenitis suppurativa in a cohort of Danish blood donors: a cross-sectional study. Br J Dermatol. 2019;180:774-781.
5. Jemec GB, Kimball AB. Hidradenitis suppurativa: epidemiology and scope of the problem. J Am Acad Dermatol. 2015;73(5 suppl 1):S4-S7.
6. Savage KT, Singh V, Patel ZS, et al. Pain management in hidradenitis suppurativa and a proposed treatment algorithm. J Am Acad Dermatol. 2021;85:187-199. doi:10.1016/j.jaad.2020.09.039
7. Alikhan A, Sayed C, Alavi A, et al. North American clinical management guidelines for hidradenitis suppurativa: a publication from the United States and Canadian Hidradenitis Suppurativa Foundations: part II: topical, intralesional, and systemic medical management. J Am Acad Dermatol. 2019;81:91-101.
8. Vellaichamy G, Braunberger TL, Nahhas AF, et al. Surgical procedures for hidradenitis suppurativa. Cutis. 2018;102:13-16.
9. Jung JM, Lee KH, Kim Y-J, et al. Assessment of overall and specific cancer risks in patients with hidradenitis suppurativa. JAMA Dermatol. 2020;156:844-853.
10. Garg A, Malviya N, Strunk A, et al. Comorbidity screening in hidradenitis suppurativa: evidence-based recommendations from the US and Canadian Hidradenitis Suppurativa Foundations. J Am Acad Dermatol. 2022;86:1092-1101. doi:10.1016/ j.jaad.2021.01.059
1. Sachdeva M, Shah M, Alavi A. Race-specific prevalence of hidradenitis suppurativa. J Cutan Med Surg. 2021;25:177-187. doi:10.1177/1203475420972348
2. Zouboulis CC, Goyal M, Byrd AS. Hidradenitis suppurativa in skin of colour. Exp Dermatol. 2021;30(suppl 1):27-30. doi:10.1111 /exd.14341
3. Shalom G, Cohen AD. The epidemiology of hidradenitis suppurativa: what do we know? Br J Dermatol. 2019;180:712-713.
4. Theut Riis P, Pedersen OB, Sigsgaard V, et al. Prevalence of patients with self-reported hidradenitis suppurativa in a cohort of Danish blood donors: a cross-sectional study. Br J Dermatol. 2019;180:774-781.
5. Jemec GB, Kimball AB. Hidradenitis suppurativa: epidemiology and scope of the problem. J Am Acad Dermatol. 2015;73(5 suppl 1):S4-S7.
6. Savage KT, Singh V, Patel ZS, et al. Pain management in hidradenitis suppurativa and a proposed treatment algorithm. J Am Acad Dermatol. 2021;85:187-199. doi:10.1016/j.jaad.2020.09.039
7. Alikhan A, Sayed C, Alavi A, et al. North American clinical management guidelines for hidradenitis suppurativa: a publication from the United States and Canadian Hidradenitis Suppurativa Foundations: part II: topical, intralesional, and systemic medical management. J Am Acad Dermatol. 2019;81:91-101.
8. Vellaichamy G, Braunberger TL, Nahhas AF, et al. Surgical procedures for hidradenitis suppurativa. Cutis. 2018;102:13-16.
9. Jung JM, Lee KH, Kim Y-J, et al. Assessment of overall and specific cancer risks in patients with hidradenitis suppurativa. JAMA Dermatol. 2020;156:844-853.
10. Garg A, Malviya N, Strunk A, et al. Comorbidity screening in hidradenitis suppurativa: evidence-based recommendations from the US and Canadian Hidradenitis Suppurativa Foundations. J Am Acad Dermatol. 2022;86:1092-1101. doi:10.1016/ j.jaad.2021.01.059
