Dermatology

Neurofibromatosis type 1 (NF1) is an autosomal dominant inherited disorder that is estimated to occur in 1:2500 births and to have a prevalence of 1:2000 to 1:4000.^1,2 It was first described in 1882 by Friedrich Daniel Von Recklinghausen, who identified patients and their relatives with signs of neuroectodermal abnormalities (café-au-lait macules [CALMs], axillary and inguinal freckling, and neurofibromas).

NF1 may begin insidiously in childhood and evolves as the patient ages. It is associated with intracranial, intraspinal, and intraorbital neoplasms, although other organs and tissues can also be involved.

The family physician might be the first one to recognize the signs of this condition during a well-child exam and is in a unique position to coordinate a multidisciplinary approach to care.

A mutated allele and early manifestations on the skin

NF1 has been attributed to genetic mosaicism and is classified as segmental, generalized, or (less frequently) gonadal. The disorder results from germline mutations in the NF1 tumor-suppressor gene on chromosome 17, known to codify the cytoplasmic protein called neurofibromin.³ The penetrance of NF1 is complete, which means that 100% of patients with the mutated allele will develop the disease.

Patients typically have symptoms by the third decade of life, although many will show signs of the disease in early childhood. CALMs are the earliest expression of NF1. They manifest in the first 2 years of life and are found in almost all affected patients. The lesions are well defined and measure 10 to 40 mm. They are typically light brown, although they may darken with sun exposure.

Histologically, the lesions will show macromelanosomes and high concentrations of melanin but do not represent an increased risk for malignancy.⁴ Not all isolated CALMs are a sign of NF1. While children younger than 29 months with 6 or more CALMs have a high risk for NF1 (80.4%; 95% confidence interval [CI], 74.6% to 86.2%), those who are older than 29 months with at least 1 atypical CALM or fewer than 6 CALMs have just a 0.9% (95% CI, 0% to 2.6%) risk for constitutional NF1.⁵

Freckles are also observed in 90% of patients with NF1; these tend to develop after the third year of life. The breast and trunk are the most commonly affected areas in adults. The pathophysiology is unknown, but this freckling is believed to be related to skin friction, high humidity, and ambient temperature.⁶

Continue to: Neurofibromas are benign...

Some patients show disfiguration when hundreds of neurofibromas are present.

Neurofibromas are benign subcutaneous palpable lesions that grow within peripheral nerve tissue, including spinal, subcutaneous, plexiform, or dermal encapsulated nerves. Originating in Schwann cells, they are composed of fibroblasts, mast cells, macrophages, endothelial cells, and other perineural cells. Some patients show disfiguration when hundreds of these masses are present (FIGURE). These tumors increase in number as the patient ages or during pregnancy, which is thought to be secondary to hormonal changes.⁷ They are sometimes painful and can be pruritic. Their appearance can also cause patient distress.

The diagnosis is a clinical one

Suspicion for NF1 should be high in patients presenting with the dermatologic findings described, although CALMs and freckling are not exclusive to NF1. Diagnostic criteria for NF1, which distinguish it from other conditions, were first outlined in a National Institutes of Health Consensus Development Conference Statement in 1987.⁸ The list of criteria has subsequently been expanded.

While the presence of at least 2 criteria is required for diagnosis,² NF1 should be suspected in individuals who have any of the following findings^8,9:

• the presence of at least 6 CALMs that are > 5 mm in prepubertal children and > 15 mm in adults
• 2 or more neurofibromas of any type, or at least one plexiform neurofibroma
• axillary or groin freckling
• optic pathway glioma
• 2 or more Lisch nodules (iris hamartomas seen on slit-lamp examination)
• bony dysplasia (sphenoid wing dysplasia, bowing of long bone ± pseudarthrosis)
• first-degree relative with NF1.

What you’ll see as the disease progresses

NF1 can affect a variety of systems, and potential complications of the disease are numerous and varied (see TABLE⁹). Here is some of what you may see as the patient’s disease progresses to various organ systems:

Learning disabilities and other cognitive and behavioral problems, such as attention-deficit/hyperactivity disorder, may affect up to 70% of children with NF1. Additionally, children with NF1 have visual/spatial problems, impaired visual motor integration, and language deficits.¹⁰ The etiology of cognitive impairment in NF1 is unknown.¹¹  

Continue to: Hypertension

Hypertension is common and may contribute to premature death in patients with NF1. Up to 27% of patients will have significant cardiovascular anomalies, including pulmonary valve stenosis, hypertrophic cardiomyopathy in patients with complete deletions of the NF1 gene, intracardiac neurofibromas, renal artery stenosis, coarctation of the aorta, and cerebral infarctions.¹² Renal artery stenosis occurs in approximately 2% of the NF1 population, and the diagnosis should be considered in hypertensive children, young adults, pregnant women, older individuals with refractory hypertension, and those with an abdominal bruit.¹³

Psychological issues. The disfigurement caused by neurofibromas and the uncertainty of an unpredictable disease course can cause psychological manifestations for patients with NF1. Anxiety and depression are common. Not surprisingly, patients with more severe disease report more adverse psychological effects.

Orthopedic deformities. Spinal deformities are the most common skeletal manifestation of NF1, with an incidence estimated from 10% to 25% in various studies. Bone mineral density, as measured by age- and gender-adjusted Z-scores, is significantly lower in NF1 patients than in the general population.¹⁴ Children may develop bowing of the long bones, particularly the tibia, and pseudarthrosis, a false joint in a long bone. Children with NF1 need yearly assessment of the spine. Patients with clinical evidence of scoliosis should be referred to Orthopedics for further evaluation.

Eye issues. A majority of adult patients develop neurofibroma-like nodules in the iris known as Lisch nodules. The nodules are not thought to cause any ophthalmologic complications. Patients may also develop palpebral neurofibroma, which may become large and sporadically show malignant transformation. Optic nerve glioma may cause strabismus and proptosis, and a large number of patients will also develop glaucoma and globe enlargement.¹⁵

Gastrointestinal lesions and cancer. Neurofibromas can grow in the stomach, liver, mesentery, retroperitoneum, and bowel. Adenocarcinoma developed in 23% of patients.¹⁶ Gastrointestinal tract bleeding, pseudo-obstruction, and protein-losing enteropathy also may occur.¹⁷

Continue to: Central nervous system manifestations

Central nervous system manifestations. Neurological manifestations have been observed in 55% of patients with NF1.¹⁸ These include headache, hydrocephalus, epilepsy, lacunar stroke, white matter disease, intraspinal neurofibroma, facial palsy, radiculopathy, and polyneuropathy. Tumors include optic pathway tumors, meningioma, and cerebral glioma. Glioma is the predominant tumor type in NF1 and occurs in all parts of the nervous system, with a predilection for the optic pathways, brainstem, and cerebellum.¹⁸

Malignant peripheral nerve sheath tumors. There is an 8% to 13% lifetime risk for malignant peripheral nerve sheath tumors (MPNST), predominantly in individuals between the ages of 20 and 35.^19,20 Any change in neurofibroma from soft to hard, or a rapid increase in the size, is suspicious for MPNST. Other symptoms include persistent pain lasting for longer than a month, pain that disturbs sleep, and new neurological deficits. These cancers can be hard to detect, leading to poor prognosis secondary to metastasis.^19,20 The greatest risk factors for MPNST are pain associated with a mass and the presence of cutaneous and subcutaneous neurofibromas.²¹

Treatment is symptom based, but there is a new option

Treatment is individualized to the patient’s symptoms. Neurofibromas that are disfiguring, disruptive, or malignant may be surgically removed.

In April 2020, the US Food and Drug Administration (FDA) approved selumetinib (Koselugo) for the treatment of pediatric patients (ages ≥ 2 years) with NF1 who have symptomatic, inoperable plexiform neurofibromas (PNs).²² In a clinical trial, patients received selumetinib 25 mg/m² orally twice a day until they demonstrated disease progression or experienced “unacceptable” adverse events.^22,23 The overall response rate was 66%, defined as “the percentage of patients with a complete response and those who experienced more than a 20% reduction in PN volume on MRI that was confirmed on a subsequent MRI within 3 to 6 months.”²²

In light of the condition’s heterogeneity, the goals of care include early recognition and treatment of complications, especially neoplasms.

Of note, all patients had a partial, not complete, response. Common adverse effects included vomiting, rash, abdominal pain, diarrhea, and nausea.²³ Selumetinib may also cause more serious adverse effects, including cardiomyopathy and ocular toxicity. Prior to treatment initiation and at regular intervals during treatment, patients should undergo cardiac and ophthalmic evaluation.^22,23 Selumetinib was granted priority review and orphan drug status by the FDA.²²

Continue to: You play a key role in ongoing monitoring

In light of the condition’s heterogeneity, the goals of care include early recognition and treatment of complications, especially neoplasms; optimization of quality of life; and identification and treatment of comorbidities. Family physicians are well positioned to monitor patients with NF1 for age-specific disease manifestations and potential complications.⁹ All patients require:

• an annual physical examination by a physician who is familiar with the individual and with the disease
• annual ophthalmologic examination in early childhood; less frequent examination in older children and adults
• regular blood pressure monitoring
• other studies (eg, MRI) only as indicated on the basis of clinically apparent signs or symptoms
• monitoring by an appropriate specialist if there are abnormalities of the central nervous, skeletal, or cardiovascular systems
• referral to a neurologist for any unexplained neurological signs and symptoms. Referral should be urgent if there are acute symptoms of progressive sensory disturbance, motor deficit and incoordination, or sphincter disturbances since these might indicate an intracranial lesion or spinal cord compression. Headaches on waking, morning vomiting, and altered consciousness are suggestive of raised intracranial pressure.

Children with NF1 benefit from coordinated care between the FP and a pediatrician or other specialist familiar with the disease. In addition to providing usual well care, perform regular assessment of development and school performance. Pay careful attention to the cardiovascular system (particularly blood pressure) and evaluate for scoliosis.

Young adults should be continually monitored for all complications, especially hypertension. This population requires continued education about NF1 and its possible complications and may benefit from counseling about disease inheritance. Screen for anxiety and depression; offer psychological support.

Provide adult patients with education about complications, especially malignant peripheral nerve sheath tumors and spinal cord compression.

Adults require monitoring based on patient preference and disease severity. For this population, blood pressure should be measured annually, or more frequently if the patient’s values indicate borderline hypertension. Provide education about complications, especially MPNSTs and spinal cord compression. Patients who have abnormalities of the central nervous, skeletal, or cardiovascular systems should be monitored by an appropriate specialist. If desired, the patient may be referred to a geneticist, especially if he or she expresses concern about inheritance. Cutaneous neurofibromas can be removed if they cause discomfort, although removal occasionally results in neurological deficit.

CORRESPONDENCE
T. Grant Phillips, MD, Associate Director, UPMC Altoona Family Physicians Residency, 501 Howard Avenue, Altoona, PA 16601-4899; [email protected]

Neurofibromatosis type 1 (NF1) is an autosomal dominant inherited disorder that is estimated to occur in 1:2500 births and to have a prevalence of 1:2000 to 1:4000.^1,2 It was first described in 1882 by Friedrich Daniel Von Recklinghausen, who identified patients and their relatives with signs of neuroectodermal abnormalities (café-au-lait macules [CALMs], axillary and inguinal freckling, and neurofibromas).

NF1 may begin insidiously in childhood and evolves as the patient ages. It is associated with intracranial, intraspinal, and intraorbital neoplasms, although other organs and tissues can also be involved.

The family physician might be the first one to recognize the signs of this condition during a well-child exam and is in a unique position to coordinate a multidisciplinary approach to care.

A mutated allele and early manifestations on the skin

NF1 has been attributed to genetic mosaicism and is classified as segmental, generalized, or (less frequently) gonadal. The disorder results from germline mutations in the NF1 tumor-suppressor gene on chromosome 17, known to codify the cytoplasmic protein called neurofibromin.³ The penetrance of NF1 is complete, which means that 100% of patients with the mutated allele will develop the disease.

Patients typically have symptoms by the third decade of life, although many will show signs of the disease in early childhood. CALMs are the earliest expression of NF1. They manifest in the first 2 years of life and are found in almost all affected patients. The lesions are well defined and measure 10 to 40 mm. They are typically light brown, although they may darken with sun exposure.

Histologically, the lesions will show macromelanosomes and high concentrations of melanin but do not represent an increased risk for malignancy.⁴ Not all isolated CALMs are a sign of NF1. While children younger than 29 months with 6 or more CALMs have a high risk for NF1 (80.4%; 95% confidence interval [CI], 74.6% to 86.2%), those who are older than 29 months with at least 1 atypical CALM or fewer than 6 CALMs have just a 0.9% (95% CI, 0% to 2.6%) risk for constitutional NF1.⁵

Freckles are also observed in 90% of patients with NF1; these tend to develop after the third year of life. The breast and trunk are the most commonly affected areas in adults. The pathophysiology is unknown, but this freckling is believed to be related to skin friction, high humidity, and ambient temperature.⁶

Continue to: Neurofibromas are benign...

Some patients show disfiguration when hundreds of neurofibromas are present.

Neurofibromas are benign subcutaneous palpable lesions that grow within peripheral nerve tissue, including spinal, subcutaneous, plexiform, or dermal encapsulated nerves. Originating in Schwann cells, they are composed of fibroblasts, mast cells, macrophages, endothelial cells, and other perineural cells. Some patients show disfiguration when hundreds of these masses are present (FIGURE). These tumors increase in number as the patient ages or during pregnancy, which is thought to be secondary to hormonal changes.⁷ They are sometimes painful and can be pruritic. Their appearance can also cause patient distress.

The diagnosis is a clinical one

Suspicion for NF1 should be high in patients presenting with the dermatologic findings described, although CALMs and freckling are not exclusive to NF1. Diagnostic criteria for NF1, which distinguish it from other conditions, were first outlined in a National Institutes of Health Consensus Development Conference Statement in 1987.⁸ The list of criteria has subsequently been expanded.

While the presence of at least 2 criteria is required for diagnosis,² NF1 should be suspected in individuals who have any of the following findings^8,9:

• the presence of at least 6 CALMs that are > 5 mm in prepubertal children and > 15 mm in adults
• 2 or more neurofibromas of any type, or at least one plexiform neurofibroma
• axillary or groin freckling
• optic pathway glioma
• 2 or more Lisch nodules (iris hamartomas seen on slit-lamp examination)
• bony dysplasia (sphenoid wing dysplasia, bowing of long bone ± pseudarthrosis)
• first-degree relative with NF1.

What you’ll see as the disease progresses

NF1 can affect a variety of systems, and potential complications of the disease are numerous and varied (see TABLE⁹). Here is some of what you may see as the patient’s disease progresses to various organ systems:

Learning disabilities and other cognitive and behavioral problems, such as attention-deficit/hyperactivity disorder, may affect up to 70% of children with NF1. Additionally, children with NF1 have visual/spatial problems, impaired visual motor integration, and language deficits.¹⁰ The etiology of cognitive impairment in NF1 is unknown.¹¹  

Continue to: Hypertension

Hypertension is common and may contribute to premature death in patients with NF1. Up to 27% of patients will have significant cardiovascular anomalies, including pulmonary valve stenosis, hypertrophic cardiomyopathy in patients with complete deletions of the NF1 gene, intracardiac neurofibromas, renal artery stenosis, coarctation of the aorta, and cerebral infarctions.¹² Renal artery stenosis occurs in approximately 2% of the NF1 population, and the diagnosis should be considered in hypertensive children, young adults, pregnant women, older individuals with refractory hypertension, and those with an abdominal bruit.¹³

Psychological issues. The disfigurement caused by neurofibromas and the uncertainty of an unpredictable disease course can cause psychological manifestations for patients with NF1. Anxiety and depression are common. Not surprisingly, patients with more severe disease report more adverse psychological effects.

Orthopedic deformities. Spinal deformities are the most common skeletal manifestation of NF1, with an incidence estimated from 10% to 25% in various studies. Bone mineral density, as measured by age- and gender-adjusted Z-scores, is significantly lower in NF1 patients than in the general population.¹⁴ Children may develop bowing of the long bones, particularly the tibia, and pseudarthrosis, a false joint in a long bone. Children with NF1 need yearly assessment of the spine. Patients with clinical evidence of scoliosis should be referred to Orthopedics for further evaluation.

Eye issues. A majority of adult patients develop neurofibroma-like nodules in the iris known as Lisch nodules. The nodules are not thought to cause any ophthalmologic complications. Patients may also develop palpebral neurofibroma, which may become large and sporadically show malignant transformation. Optic nerve glioma may cause strabismus and proptosis, and a large number of patients will also develop glaucoma and globe enlargement.¹⁵

Gastrointestinal lesions and cancer. Neurofibromas can grow in the stomach, liver, mesentery, retroperitoneum, and bowel. Adenocarcinoma developed in 23% of patients.¹⁶ Gastrointestinal tract bleeding, pseudo-obstruction, and protein-losing enteropathy also may occur.¹⁷

Continue to: Central nervous system manifestations

Central nervous system manifestations. Neurological manifestations have been observed in 55% of patients with NF1.¹⁸ These include headache, hydrocephalus, epilepsy, lacunar stroke, white matter disease, intraspinal neurofibroma, facial palsy, radiculopathy, and polyneuropathy. Tumors include optic pathway tumors, meningioma, and cerebral glioma. Glioma is the predominant tumor type in NF1 and occurs in all parts of the nervous system, with a predilection for the optic pathways, brainstem, and cerebellum.¹⁸

Malignant peripheral nerve sheath tumors. There is an 8% to 13% lifetime risk for malignant peripheral nerve sheath tumors (MPNST), predominantly in individuals between the ages of 20 and 35.^19,20 Any change in neurofibroma from soft to hard, or a rapid increase in the size, is suspicious for MPNST. Other symptoms include persistent pain lasting for longer than a month, pain that disturbs sleep, and new neurological deficits. These cancers can be hard to detect, leading to poor prognosis secondary to metastasis.^19,20 The greatest risk factors for MPNST are pain associated with a mass and the presence of cutaneous and subcutaneous neurofibromas.²¹

Treatment is symptom based, but there is a new option

Treatment is individualized to the patient’s symptoms. Neurofibromas that are disfiguring, disruptive, or malignant may be surgically removed.

In April 2020, the US Food and Drug Administration (FDA) approved selumetinib (Koselugo) for the treatment of pediatric patients (ages ≥ 2 years) with NF1 who have symptomatic, inoperable plexiform neurofibromas (PNs).²² In a clinical trial, patients received selumetinib 25 mg/m² orally twice a day until they demonstrated disease progression or experienced “unacceptable” adverse events.^22,23 The overall response rate was 66%, defined as “the percentage of patients with a complete response and those who experienced more than a 20% reduction in PN volume on MRI that was confirmed on a subsequent MRI within 3 to 6 months.”²²

In light of the condition’s heterogeneity, the goals of care include early recognition and treatment of complications, especially neoplasms.

Of note, all patients had a partial, not complete, response. Common adverse effects included vomiting, rash, abdominal pain, diarrhea, and nausea.²³ Selumetinib may also cause more serious adverse effects, including cardiomyopathy and ocular toxicity. Prior to treatment initiation and at regular intervals during treatment, patients should undergo cardiac and ophthalmic evaluation.^22,23 Selumetinib was granted priority review and orphan drug status by the FDA.²²

Continue to: You play a key role in ongoing monitoring

In light of the condition’s heterogeneity, the goals of care include early recognition and treatment of complications, especially neoplasms; optimization of quality of life; and identification and treatment of comorbidities. Family physicians are well positioned to monitor patients with NF1 for age-specific disease manifestations and potential complications.⁹ All patients require:

• an annual physical examination by a physician who is familiar with the individual and with the disease
• annual ophthalmologic examination in early childhood; less frequent examination in older children and adults
• regular blood pressure monitoring
• other studies (eg, MRI) only as indicated on the basis of clinically apparent signs or symptoms
• monitoring by an appropriate specialist if there are abnormalities of the central nervous, skeletal, or cardiovascular systems
• referral to a neurologist for any unexplained neurological signs and symptoms. Referral should be urgent if there are acute symptoms of progressive sensory disturbance, motor deficit and incoordination, or sphincter disturbances since these might indicate an intracranial lesion or spinal cord compression. Headaches on waking, morning vomiting, and altered consciousness are suggestive of raised intracranial pressure.

Children with NF1 benefit from coordinated care between the FP and a pediatrician or other specialist familiar with the disease. In addition to providing usual well care, perform regular assessment of development and school performance. Pay careful attention to the cardiovascular system (particularly blood pressure) and evaluate for scoliosis.

Young adults should be continually monitored for all complications, especially hypertension. This population requires continued education about NF1 and its possible complications and may benefit from counseling about disease inheritance. Screen for anxiety and depression; offer psychological support.

Provide adult patients with education about complications, especially malignant peripheral nerve sheath tumors and spinal cord compression.

Adults require monitoring based on patient preference and disease severity. For this population, blood pressure should be measured annually, or more frequently if the patient’s values indicate borderline hypertension. Provide education about complications, especially MPNSTs and spinal cord compression. Patients who have abnormalities of the central nervous, skeletal, or cardiovascular systems should be monitored by an appropriate specialist. If desired, the patient may be referred to a geneticist, especially if he or she expresses concern about inheritance. Cutaneous neurofibromas can be removed if they cause discomfort, although removal occasionally results in neurological deficit.

CORRESPONDENCE
T. Grant Phillips, MD, Associate Director, UPMC Altoona Family Physicians Residency, 501 Howard Avenue, Altoona, PA 16601-4899; [email protected]

Neurofibromatosis type 1 (NF1) is an autosomal dominant inherited disorder that is estimated to occur in 1:2500 births and to have a prevalence of 1:2000 to 1:4000.^1,2 It was first described in 1882 by Friedrich Daniel Von Recklinghausen, who identified patients and their relatives with signs of neuroectodermal abnormalities (café-au-lait macules [CALMs], axillary and inguinal freckling, and neurofibromas).

NF1 may begin insidiously in childhood and evolves as the patient ages. It is associated with intracranial, intraspinal, and intraorbital neoplasms, although other organs and tissues can also be involved.

The family physician might be the first one to recognize the signs of this condition during a well-child exam and is in a unique position to coordinate a multidisciplinary approach to care.

A mutated allele and early manifestations on the skin

NF1 has been attributed to genetic mosaicism and is classified as segmental, generalized, or (less frequently) gonadal. The disorder results from germline mutations in the NF1 tumor-suppressor gene on chromosome 17, known to codify the cytoplasmic protein called neurofibromin.³ The penetrance of NF1 is complete, which means that 100% of patients with the mutated allele will develop the disease.

Patients typically have symptoms by the third decade of life, although many will show signs of the disease in early childhood. CALMs are the earliest expression of NF1. They manifest in the first 2 years of life and are found in almost all affected patients. The lesions are well defined and measure 10 to 40 mm. They are typically light brown, although they may darken with sun exposure.

Histologically, the lesions will show macromelanosomes and high concentrations of melanin but do not represent an increased risk for malignancy.⁴ Not all isolated CALMs are a sign of NF1. While children younger than 29 months with 6 or more CALMs have a high risk for NF1 (80.4%; 95% confidence interval [CI], 74.6% to 86.2%), those who are older than 29 months with at least 1 atypical CALM or fewer than 6 CALMs have just a 0.9% (95% CI, 0% to 2.6%) risk for constitutional NF1.⁵

Freckles are also observed in 90% of patients with NF1; these tend to develop after the third year of life. The breast and trunk are the most commonly affected areas in adults. The pathophysiology is unknown, but this freckling is believed to be related to skin friction, high humidity, and ambient temperature.⁶

Continue to: Neurofibromas are benign...

Some patients show disfiguration when hundreds of neurofibromas are present.

Neurofibromas are benign subcutaneous palpable lesions that grow within peripheral nerve tissue, including spinal, subcutaneous, plexiform, or dermal encapsulated nerves. Originating in Schwann cells, they are composed of fibroblasts, mast cells, macrophages, endothelial cells, and other perineural cells. Some patients show disfiguration when hundreds of these masses are present (FIGURE). These tumors increase in number as the patient ages or during pregnancy, which is thought to be secondary to hormonal changes.⁷ They are sometimes painful and can be pruritic. Their appearance can also cause patient distress.

The diagnosis is a clinical one

Suspicion for NF1 should be high in patients presenting with the dermatologic findings described, although CALMs and freckling are not exclusive to NF1. Diagnostic criteria for NF1, which distinguish it from other conditions, were first outlined in a National Institutes of Health Consensus Development Conference Statement in 1987.⁸ The list of criteria has subsequently been expanded.

While the presence of at least 2 criteria is required for diagnosis,² NF1 should be suspected in individuals who have any of the following findings^8,9:

• the presence of at least 6 CALMs that are > 5 mm in prepubertal children and > 15 mm in adults
• 2 or more neurofibromas of any type, or at least one plexiform neurofibroma
• axillary or groin freckling
• optic pathway glioma
• 2 or more Lisch nodules (iris hamartomas seen on slit-lamp examination)
• bony dysplasia (sphenoid wing dysplasia, bowing of long bone ± pseudarthrosis)
• first-degree relative with NF1.

What you’ll see as the disease progresses

NF1 can affect a variety of systems, and potential complications of the disease are numerous and varied (see TABLE⁹). Here is some of what you may see as the patient’s disease progresses to various organ systems:

Learning disabilities and other cognitive and behavioral problems, such as attention-deficit/hyperactivity disorder, may affect up to 70% of children with NF1. Additionally, children with NF1 have visual/spatial problems, impaired visual motor integration, and language deficits.¹⁰ The etiology of cognitive impairment in NF1 is unknown.¹¹  

Continue to: Hypertension

Hypertension is common and may contribute to premature death in patients with NF1. Up to 27% of patients will have significant cardiovascular anomalies, including pulmonary valve stenosis, hypertrophic cardiomyopathy in patients with complete deletions of the NF1 gene, intracardiac neurofibromas, renal artery stenosis, coarctation of the aorta, and cerebral infarctions.¹² Renal artery stenosis occurs in approximately 2% of the NF1 population, and the diagnosis should be considered in hypertensive children, young adults, pregnant women, older individuals with refractory hypertension, and those with an abdominal bruit.¹³

Psychological issues. The disfigurement caused by neurofibromas and the uncertainty of an unpredictable disease course can cause psychological manifestations for patients with NF1. Anxiety and depression are common. Not surprisingly, patients with more severe disease report more adverse psychological effects.

Orthopedic deformities. Spinal deformities are the most common skeletal manifestation of NF1, with an incidence estimated from 10% to 25% in various studies. Bone mineral density, as measured by age- and gender-adjusted Z-scores, is significantly lower in NF1 patients than in the general population.¹⁴ Children may develop bowing of the long bones, particularly the tibia, and pseudarthrosis, a false joint in a long bone. Children with NF1 need yearly assessment of the spine. Patients with clinical evidence of scoliosis should be referred to Orthopedics for further evaluation.

Eye issues. A majority of adult patients develop neurofibroma-like nodules in the iris known as Lisch nodules. The nodules are not thought to cause any ophthalmologic complications. Patients may also develop palpebral neurofibroma, which may become large and sporadically show malignant transformation. Optic nerve glioma may cause strabismus and proptosis, and a large number of patients will also develop glaucoma and globe enlargement.¹⁵

Gastrointestinal lesions and cancer. Neurofibromas can grow in the stomach, liver, mesentery, retroperitoneum, and bowel. Adenocarcinoma developed in 23% of patients.¹⁶ Gastrointestinal tract bleeding, pseudo-obstruction, and protein-losing enteropathy also may occur.¹⁷

Continue to: Central nervous system manifestations

Central nervous system manifestations. Neurological manifestations have been observed in 55% of patients with NF1.¹⁸ These include headache, hydrocephalus, epilepsy, lacunar stroke, white matter disease, intraspinal neurofibroma, facial palsy, radiculopathy, and polyneuropathy. Tumors include optic pathway tumors, meningioma, and cerebral glioma. Glioma is the predominant tumor type in NF1 and occurs in all parts of the nervous system, with a predilection for the optic pathways, brainstem, and cerebellum.¹⁸

Malignant peripheral nerve sheath tumors. There is an 8% to 13% lifetime risk for malignant peripheral nerve sheath tumors (MPNST), predominantly in individuals between the ages of 20 and 35.^19,20 Any change in neurofibroma from soft to hard, or a rapid increase in the size, is suspicious for MPNST. Other symptoms include persistent pain lasting for longer than a month, pain that disturbs sleep, and new neurological deficits. These cancers can be hard to detect, leading to poor prognosis secondary to metastasis.^19,20 The greatest risk factors for MPNST are pain associated with a mass and the presence of cutaneous and subcutaneous neurofibromas.²¹

Treatment is symptom based, but there is a new option

Treatment is individualized to the patient’s symptoms. Neurofibromas that are disfiguring, disruptive, or malignant may be surgically removed.

In April 2020, the US Food and Drug Administration (FDA) approved selumetinib (Koselugo) for the treatment of pediatric patients (ages ≥ 2 years) with NF1 who have symptomatic, inoperable plexiform neurofibromas (PNs).²² In a clinical trial, patients received selumetinib 25 mg/m² orally twice a day until they demonstrated disease progression or experienced “unacceptable” adverse events.^22,23 The overall response rate was 66%, defined as “the percentage of patients with a complete response and those who experienced more than a 20% reduction in PN volume on MRI that was confirmed on a subsequent MRI within 3 to 6 months.”²²

In light of the condition’s heterogeneity, the goals of care include early recognition and treatment of complications, especially neoplasms.

Of note, all patients had a partial, not complete, response. Common adverse effects included vomiting, rash, abdominal pain, diarrhea, and nausea.²³ Selumetinib may also cause more serious adverse effects, including cardiomyopathy and ocular toxicity. Prior to treatment initiation and at regular intervals during treatment, patients should undergo cardiac and ophthalmic evaluation.^22,23 Selumetinib was granted priority review and orphan drug status by the FDA.²²

Continue to: You play a key role in ongoing monitoring

In light of the condition’s heterogeneity, the goals of care include early recognition and treatment of complications, especially neoplasms; optimization of quality of life; and identification and treatment of comorbidities. Family physicians are well positioned to monitor patients with NF1 for age-specific disease manifestations and potential complications.⁹ All patients require:

• an annual physical examination by a physician who is familiar with the individual and with the disease
• annual ophthalmologic examination in early childhood; less frequent examination in older children and adults
• regular blood pressure monitoring
• other studies (eg, MRI) only as indicated on the basis of clinically apparent signs or symptoms
• monitoring by an appropriate specialist if there are abnormalities of the central nervous, skeletal, or cardiovascular systems
• referral to a neurologist for any unexplained neurological signs and symptoms. Referral should be urgent if there are acute symptoms of progressive sensory disturbance, motor deficit and incoordination, or sphincter disturbances since these might indicate an intracranial lesion or spinal cord compression. Headaches on waking, morning vomiting, and altered consciousness are suggestive of raised intracranial pressure.

Children with NF1 benefit from coordinated care between the FP and a pediatrician or other specialist familiar with the disease. In addition to providing usual well care, perform regular assessment of development and school performance. Pay careful attention to the cardiovascular system (particularly blood pressure) and evaluate for scoliosis.

Young adults should be continually monitored for all complications, especially hypertension. This population requires continued education about NF1 and its possible complications and may benefit from counseling about disease inheritance. Screen for anxiety and depression; offer psychological support.

Provide adult patients with education about complications, especially malignant peripheral nerve sheath tumors and spinal cord compression.

Adults require monitoring based on patient preference and disease severity. For this population, blood pressure should be measured annually, or more frequently if the patient’s values indicate borderline hypertension. Provide education about complications, especially MPNSTs and spinal cord compression. Patients who have abnormalities of the central nervous, skeletal, or cardiovascular systems should be monitored by an appropriate specialist. If desired, the patient may be referred to a geneticist, especially if he or she expresses concern about inheritance. Cutaneous neurofibromas can be removed if they cause discomfort, although removal occasionally results in neurological deficit.

CORRESPONDENCE
T. Grant Phillips, MD, Associate Director, UPMC Altoona Family Physicians Residency, 501 Howard Avenue, Altoona, PA 16601-4899; [email protected]

Prurigo pigmentosa is an inflammatory disorder of uncertain etiology characterized by the eruption of erythematous, markedly pruritic, urticaria-like papules and vesicles on the posterior neck, mid- to upper back, and chest. Crops of papules appear rapidly and then involute within days, leaving behind postinflammatory hyperpigmentation in a netlike configuration. New papules may appear prior to resolution of hyperpigmented macules, resulting in a mixed presentation of erythematous papules overlying reticulated hyperpigmentation.¹

The condition was initially described in Japanese individuals, and to date, most cases have occurred in this population.² However, the incidence of prurigo pigmentosa is increasing worldwide, including in the United States, which has led to the identification of several metabolic risk factors including diabetes mellitus, fasting, and dieting, with the common etiologic endpoint of ketosis.³With the increasing popularity of diets with strict carbohydrate limits, often with the goal of ketosis, dermatologists should be aware of the clinical appearance and common history of this rash to facilitate prompt diagnosis and treatment.

Clinical exam with appropriate history is usually sufficient for diagnosis. However, biopsy with histopathologic analysis can be utilized to confirm atypical cases. Histopathologic findings depend on the stage of the lesion biopsied. The earliest finding is a shallow perivascular neutrophilic infiltrate, neutrophil exocytosis, and epidermal and superficial dermal edema. As lesions progress, the prominent findings include epidermal vesiculation with necrotic keratinocytes and a lichenoid infiltrate dominated by lymphocytes and eosinophils. In the final stages, lesions demonstrate variable parakeratosis and acanthosis, as well as prominent dermal melanophagia.¹

Treatment of prurigo pigmentosa includes modification of the patient’s underlying health issues to avoid ketosis, and in the case of diet-induced ketosis, reinstitution of a more balanced diet with sufficient carbohydrates. In the case of the patient presented here, rash resolved 1 week following instruction to include more carbohydrates in his diet. For recalcitrant cases or those without a clear precipitating factor, the addition of oral antibiotics is often helpful. Tetracyclines or dapsone are typically employed, usually in courses of 1-2 months.^3,4
 

Dr. Johnson is a PGY-4 dermatology resident at Carilion Clinic in Roanoke, Va. He provided the case and photos. Donna Bilu Martin, MD, is the editor of the column.

References

1. Boer A et al. Am J Dermatopathol. 2003 Apr;25(2):117-292.

2. Satter E et al. J Cutan Pathol. 2016 Oct;43(10):809-14.

3. Alshaya M et al. JAAD Case Rep. 2019 Jun 8;5(6):504-7.

4. Hartman M et al. Cutis. 2019 Mar;103(3):E10-3.

Prurigo pigmentosa is an inflammatory disorder of uncertain etiology characterized by the eruption of erythematous, markedly pruritic, urticaria-like papules and vesicles on the posterior neck, mid- to upper back, and chest. Crops of papules appear rapidly and then involute within days, leaving behind postinflammatory hyperpigmentation in a netlike configuration. New papules may appear prior to resolution of hyperpigmented macules, resulting in a mixed presentation of erythematous papules overlying reticulated hyperpigmentation.¹

The condition was initially described in Japanese individuals, and to date, most cases have occurred in this population.² However, the incidence of prurigo pigmentosa is increasing worldwide, including in the United States, which has led to the identification of several metabolic risk factors including diabetes mellitus, fasting, and dieting, with the common etiologic endpoint of ketosis.³With the increasing popularity of diets with strict carbohydrate limits, often with the goal of ketosis, dermatologists should be aware of the clinical appearance and common history of this rash to facilitate prompt diagnosis and treatment.

Clinical exam with appropriate history is usually sufficient for diagnosis. However, biopsy with histopathologic analysis can be utilized to confirm atypical cases. Histopathologic findings depend on the stage of the lesion biopsied. The earliest finding is a shallow perivascular neutrophilic infiltrate, neutrophil exocytosis, and epidermal and superficial dermal edema. As lesions progress, the prominent findings include epidermal vesiculation with necrotic keratinocytes and a lichenoid infiltrate dominated by lymphocytes and eosinophils. In the final stages, lesions demonstrate variable parakeratosis and acanthosis, as well as prominent dermal melanophagia.¹

Treatment of prurigo pigmentosa includes modification of the patient’s underlying health issues to avoid ketosis, and in the case of diet-induced ketosis, reinstitution of a more balanced diet with sufficient carbohydrates. In the case of the patient presented here, rash resolved 1 week following instruction to include more carbohydrates in his diet. For recalcitrant cases or those without a clear precipitating factor, the addition of oral antibiotics is often helpful. Tetracyclines or dapsone are typically employed, usually in courses of 1-2 months.^3,4
 

Dr. Johnson is a PGY-4 dermatology resident at Carilion Clinic in Roanoke, Va. He provided the case and photos. Donna Bilu Martin, MD, is the editor of the column.

References

1. Boer A et al. Am J Dermatopathol. 2003 Apr;25(2):117-292.

2. Satter E et al. J Cutan Pathol. 2016 Oct;43(10):809-14.

3. Alshaya M et al. JAAD Case Rep. 2019 Jun 8;5(6):504-7.

4. Hartman M et al. Cutis. 2019 Mar;103(3):E10-3.

Prurigo pigmentosa is an inflammatory disorder of uncertain etiology characterized by the eruption of erythematous, markedly pruritic, urticaria-like papules and vesicles on the posterior neck, mid- to upper back, and chest. Crops of papules appear rapidly and then involute within days, leaving behind postinflammatory hyperpigmentation in a netlike configuration. New papules may appear prior to resolution of hyperpigmented macules, resulting in a mixed presentation of erythematous papules overlying reticulated hyperpigmentation.¹

The condition was initially described in Japanese individuals, and to date, most cases have occurred in this population.² However, the incidence of prurigo pigmentosa is increasing worldwide, including in the United States, which has led to the identification of several metabolic risk factors including diabetes mellitus, fasting, and dieting, with the common etiologic endpoint of ketosis.³With the increasing popularity of diets with strict carbohydrate limits, often with the goal of ketosis, dermatologists should be aware of the clinical appearance and common history of this rash to facilitate prompt diagnosis and treatment.

Clinical exam with appropriate history is usually sufficient for diagnosis. However, biopsy with histopathologic analysis can be utilized to confirm atypical cases. Histopathologic findings depend on the stage of the lesion biopsied. The earliest finding is a shallow perivascular neutrophilic infiltrate, neutrophil exocytosis, and epidermal and superficial dermal edema. As lesions progress, the prominent findings include epidermal vesiculation with necrotic keratinocytes and a lichenoid infiltrate dominated by lymphocytes and eosinophils. In the final stages, lesions demonstrate variable parakeratosis and acanthosis, as well as prominent dermal melanophagia.¹

Treatment of prurigo pigmentosa includes modification of the patient’s underlying health issues to avoid ketosis, and in the case of diet-induced ketosis, reinstitution of a more balanced diet with sufficient carbohydrates. In the case of the patient presented here, rash resolved 1 week following instruction to include more carbohydrates in his diet. For recalcitrant cases or those without a clear precipitating factor, the addition of oral antibiotics is often helpful. Tetracyclines or dapsone are typically employed, usually in courses of 1-2 months.^3,4
 

Dr. Johnson is a PGY-4 dermatology resident at Carilion Clinic in Roanoke, Va. He provided the case and photos. Donna Bilu Martin, MD, is the editor of the column.

References

1. Boer A et al. Am J Dermatopathol. 2003 Apr;25(2):117-292.

2. Satter E et al. J Cutan Pathol. 2016 Oct;43(10):809-14.

3. Alshaya M et al. JAAD Case Rep. 2019 Jun 8;5(6):504-7.

4. Hartman M et al. Cutis. 2019 Mar;103(3):E10-3.

An 80-year-old woman with a history of hypertension, hyperlipidemia, psoriasis vulgaris with associated pruritus, and well-controlled type 2 diabetes mellitus presented with a slowly enlarging ulceration on her left leg of 1 year’s duration. She noted that this lesion healed less rapidly than previous stasis leg ulcerations, despite using the same treatment approach that included dressings, elevation, and diuretics to decrease pedal edema.

Physical examination revealed plaques with white micaceous scaling over her extensor surfaces and scalp, as well as guttate lesions on the trunk, typical of psoriasis vulgaris. A 5.8 × 7.2-cm malodorous ulceration was superimposed on a large psoriatic plaque on her left anterior lower leg (FIGURE 1). A 4-mm punch biopsy was obtained from the peripheral margin.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Histopathological examination revealed elongated strands of closely packed basaloid cells embedded in a dense fibrous stroma with overlying ulceration and crusting (FIGURE 2). Immunohistochemical staining with cytokeratin (CK) 5/6 decorated the cytoplasm of the tumor cells, which confirmed that the tumor was a keratinocyte cancer. CK 20 was negative, excluding the possibility of a Merkel cell carcinoma. Scout biopsies from 3 additional areas of ulceration confirmed that the entire ulceration was infiltrated by basal cell carcinoma (BCC).

IMAGE COURTESY OF ROBERT BRODELL, MD

A surprise hidden in a chronic ulcer

More than 6 million Americans have chronic ulcers and most occur on the legs.¹ The majority of these chronic ulcerations are etiologically related to venous stasis, arterial insufficiency, or neuropathy.²

Bacterial pyoderma, chronic infection caused by atypical acid-fast bacilli or deep fungal infection, pyoderma gangrenosum, cutaneous vasculitis, calciphylaxis, and venous ulceration were all considered to explain this patient’s nonhealing wound. A biopsy was required to fully assess these possibilities.

Don’t overlook the possibility of malignancy. In a cross-sectional, multicenter study by Senet et al,³ 144 patients with 154 total chronic leg ulcers were evaluated in tertiary care centers for malignancy, which was found to occur at a rate of 10.4%. Similarly, Ghasemi et al⁴ demonstrated a malignancy rate of 16.1% in 124 patients who underwent biopsy; the anterior shin was determined to be the most frequent location for malignancy. The most common skin cancer identified within the setting of chronic ulcers is squamous cell carcinoma.³ Although rare, there are reports of BCC identified in chronic wounds.^3-7

Morphological signs suggestive of malignancy in chronic ulcerations include hyperkeratosis, granulation tissue surrounded by a raised border, unusual pain or bleeding, and increased tissue friability. Our patient had none of these signs and symptoms. However, it is possible that she had a tumor that ulcerated and would not heal.

Continue to: Which came first?

Which came first? It’s difficult to know in this case whether a persistent BCC ulcerated, forming this lesion, or if scarring associated with a chronic ulceration led to the development of the BCC.⁶ Based on biopsies taken at an earlier date, Schnirring-Judge and Belpedio⁷ concluded that a chronic leg ulcer could, indeed, transform into a BCC; however, pre-existing BCC more commonly ulcerates and then does not heal.

Treatment options

While smaller, superficial BCCs can be treated with topical imiquimod, photodynamic therapy, or electrodesiccation and curettage, larger lesions should be treated with Mohs micrographic surgery and excisional surgery with grafting. Inoperable tumors may be treated with radiation therapy and vismodegib.

Our patient. Once the diagnosis of BCC was established, treatment options were discussed, including excision, local radiation therapy, and oral hedgehog inhibitor drug therapy.⁸ Our patient opted to undergo a wide local excision of the lesion followed by negative-pressure wound therapy, which led to complete healing.

CORRESPONDENCE
David Crasto, DO, William Carey University College of Osteopathic Medicine, 498 Tuscan Avenue, Hattiesburg, MS 39401; [email protected]

An 80-year-old woman with a history of hypertension, hyperlipidemia, psoriasis vulgaris with associated pruritus, and well-controlled type 2 diabetes mellitus presented with a slowly enlarging ulceration on her left leg of 1 year’s duration. She noted that this lesion healed less rapidly than previous stasis leg ulcerations, despite using the same treatment approach that included dressings, elevation, and diuretics to decrease pedal edema.

Physical examination revealed plaques with white micaceous scaling over her extensor surfaces and scalp, as well as guttate lesions on the trunk, typical of psoriasis vulgaris. A 5.8 × 7.2-cm malodorous ulceration was superimposed on a large psoriatic plaque on her left anterior lower leg (FIGURE 1). A 4-mm punch biopsy was obtained from the peripheral margin.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Histopathological examination revealed elongated strands of closely packed basaloid cells embedded in a dense fibrous stroma with overlying ulceration and crusting (FIGURE 2). Immunohistochemical staining with cytokeratin (CK) 5/6 decorated the cytoplasm of the tumor cells, which confirmed that the tumor was a keratinocyte cancer. CK 20 was negative, excluding the possibility of a Merkel cell carcinoma. Scout biopsies from 3 additional areas of ulceration confirmed that the entire ulceration was infiltrated by basal cell carcinoma (BCC).

IMAGE COURTESY OF ROBERT BRODELL, MD

A surprise hidden in a chronic ulcer

More than 6 million Americans have chronic ulcers and most occur on the legs.¹ The majority of these chronic ulcerations are etiologically related to venous stasis, arterial insufficiency, or neuropathy.²

Bacterial pyoderma, chronic infection caused by atypical acid-fast bacilli or deep fungal infection, pyoderma gangrenosum, cutaneous vasculitis, calciphylaxis, and venous ulceration were all considered to explain this patient’s nonhealing wound. A biopsy was required to fully assess these possibilities.

Don’t overlook the possibility of malignancy. In a cross-sectional, multicenter study by Senet et al,³ 144 patients with 154 total chronic leg ulcers were evaluated in tertiary care centers for malignancy, which was found to occur at a rate of 10.4%. Similarly, Ghasemi et al⁴ demonstrated a malignancy rate of 16.1% in 124 patients who underwent biopsy; the anterior shin was determined to be the most frequent location for malignancy. The most common skin cancer identified within the setting of chronic ulcers is squamous cell carcinoma.³ Although rare, there are reports of BCC identified in chronic wounds.^3-7

Morphological signs suggestive of malignancy in chronic ulcerations include hyperkeratosis, granulation tissue surrounded by a raised border, unusual pain or bleeding, and increased tissue friability. Our patient had none of these signs and symptoms. However, it is possible that she had a tumor that ulcerated and would not heal.

Continue to: Which came first?

Which came first? It’s difficult to know in this case whether a persistent BCC ulcerated, forming this lesion, or if scarring associated with a chronic ulceration led to the development of the BCC.⁶ Based on biopsies taken at an earlier date, Schnirring-Judge and Belpedio⁷ concluded that a chronic leg ulcer could, indeed, transform into a BCC; however, pre-existing BCC more commonly ulcerates and then does not heal.

Treatment options

While smaller, superficial BCCs can be treated with topical imiquimod, photodynamic therapy, or electrodesiccation and curettage, larger lesions should be treated with Mohs micrographic surgery and excisional surgery with grafting. Inoperable tumors may be treated with radiation therapy and vismodegib.

Our patient. Once the diagnosis of BCC was established, treatment options were discussed, including excision, local radiation therapy, and oral hedgehog inhibitor drug therapy.⁸ Our patient opted to undergo a wide local excision of the lesion followed by negative-pressure wound therapy, which led to complete healing.

CORRESPONDENCE
David Crasto, DO, William Carey University College of Osteopathic Medicine, 498 Tuscan Avenue, Hattiesburg, MS 39401; [email protected]

An 80-year-old woman with a history of hypertension, hyperlipidemia, psoriasis vulgaris with associated pruritus, and well-controlled type 2 diabetes mellitus presented with a slowly enlarging ulceration on her left leg of 1 year’s duration. She noted that this lesion healed less rapidly than previous stasis leg ulcerations, despite using the same treatment approach that included dressings, elevation, and diuretics to decrease pedal edema.

Physical examination revealed plaques with white micaceous scaling over her extensor surfaces and scalp, as well as guttate lesions on the trunk, typical of psoriasis vulgaris. A 5.8 × 7.2-cm malodorous ulceration was superimposed on a large psoriatic plaque on her left anterior lower leg (FIGURE 1). A 4-mm punch biopsy was obtained from the peripheral margin.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Histopathological examination revealed elongated strands of closely packed basaloid cells embedded in a dense fibrous stroma with overlying ulceration and crusting (FIGURE 2). Immunohistochemical staining with cytokeratin (CK) 5/6 decorated the cytoplasm of the tumor cells, which confirmed that the tumor was a keratinocyte cancer. CK 20 was negative, excluding the possibility of a Merkel cell carcinoma. Scout biopsies from 3 additional areas of ulceration confirmed that the entire ulceration was infiltrated by basal cell carcinoma (BCC).

IMAGE COURTESY OF ROBERT BRODELL, MD

A surprise hidden in a chronic ulcer

More than 6 million Americans have chronic ulcers and most occur on the legs.¹ The majority of these chronic ulcerations are etiologically related to venous stasis, arterial insufficiency, or neuropathy.²

Bacterial pyoderma, chronic infection caused by atypical acid-fast bacilli or deep fungal infection, pyoderma gangrenosum, cutaneous vasculitis, calciphylaxis, and venous ulceration were all considered to explain this patient’s nonhealing wound. A biopsy was required to fully assess these possibilities.

Don’t overlook the possibility of malignancy. In a cross-sectional, multicenter study by Senet et al,³ 144 patients with 154 total chronic leg ulcers were evaluated in tertiary care centers for malignancy, which was found to occur at a rate of 10.4%. Similarly, Ghasemi et al⁴ demonstrated a malignancy rate of 16.1% in 124 patients who underwent biopsy; the anterior shin was determined to be the most frequent location for malignancy. The most common skin cancer identified within the setting of chronic ulcers is squamous cell carcinoma.³ Although rare, there are reports of BCC identified in chronic wounds.^3-7

Morphological signs suggestive of malignancy in chronic ulcerations include hyperkeratosis, granulation tissue surrounded by a raised border, unusual pain or bleeding, and increased tissue friability. Our patient had none of these signs and symptoms. However, it is possible that she had a tumor that ulcerated and would not heal.

Continue to: Which came first?

Which came first? It’s difficult to know in this case whether a persistent BCC ulcerated, forming this lesion, or if scarring associated with a chronic ulceration led to the development of the BCC.⁶ Based on biopsies taken at an earlier date, Schnirring-Judge and Belpedio⁷ concluded that a chronic leg ulcer could, indeed, transform into a BCC; however, pre-existing BCC more commonly ulcerates and then does not heal.

Treatment options

While smaller, superficial BCCs can be treated with topical imiquimod, photodynamic therapy, or electrodesiccation and curettage, larger lesions should be treated with Mohs micrographic surgery and excisional surgery with grafting. Inoperable tumors may be treated with radiation therapy and vismodegib.

Our patient. Once the diagnosis of BCC was established, treatment options were discussed, including excision, local radiation therapy, and oral hedgehog inhibitor drug therapy.⁸ Our patient opted to undergo a wide local excision of the lesion followed by negative-pressure wound therapy, which led to complete healing.

CORRESPONDENCE
David Crasto, DO, William Carey University College of Osteopathic Medicine, 498 Tuscan Avenue, Hattiesburg, MS 39401; [email protected]

Ultrapotent topical corticosteroids remain the core treatment for vulvar lichen sclerosus, although other therapies can be added, according to an expert speaking at the virtual conference on diseases of the vulva and vagina.

If needed, intralesional steroid injections or calcineurin inhibitors can be added to a topical corticosteroid regimen, Libby Edwards, MD, suggested at the meeting, hosted by the International Society for the Study of Vulvovaginal Disease. In addition, early reports indicate that newer interventions such as fractional CO₂ laser treatments may help patients with refractory disease.

Still, “there is no question, there is no argument: First-, second- and third-line treatment for lichen sclerosus is an ultrapotent or superpotent topical corticosteroid,” she said. Steroids include halobetasol, clobetasol, or betamethasone dipropionate in augmented vehicle ointment once or twice per day. Patients should continue this regimen until the skin texture is normal or the disease is controlled as well as possible, which usually takes several months, said Dr. Edwards, of Southeast Vulvar Clinic in Charlotte, N.C.

Patients then should continue treatment, but less frequently or with a lower potency steroid.

Although corticosteroids are not Food and Drug Administration–approved for the treatment of lichen sclerosus, double-blind, placebo-controlled trials support their use, Dr. Edwards said.

Getting patients to use topical corticosteroids as directed can be a challenge, however, and patient education is crucial.

After about 10 days, many patients start to feel better and stop the medication prematurely, which may lead to recurrence.

“That is such an important counseling point,” Aruna Venkatesan, MD, chief of dermatology and director of the genital dermatology clinic at Santa Clara Valley Medical Center in San Jose, Calif., said during a panel discussion. “Tell them, listen, I may not see you back for a couple months, and you may start feeling better sooner. But I want you to keep using this at this frequency so that when you come back we can make a good decision about whether you’re ready” for a lower potency regimen.

To encourage daily use, Hope K. Haefner, MD, asks patients whether they brush their teeth every night. “When they say yes, I tell them to put the steroid ointment by their toothpaste and use it after brushing,” Dr. Haefner, the Harold A. Furlong Professor of Women’s Health at Michigan Medicine in Ann Arbor, said during the discussion. “But don’t mix up the tubes.”

Once lichen sclerosus is controlled, options include decreasing the superpotent steroid to once, three times per week or changing to a midpotency steroid such as triamcinolone ointment every day, Dr. Edwards said.

Evidence suggests that controlling lichen sclerosus may prevent squamous cell carcinoma and scarring. In a study of more than 500 patients, about 70% complied with treatment instructions, whereas about 30% were considered partially compliant (JAMA Dermatol. 2015 Oct;151[10]:1061-7.). Patients who adhered to their therapy were less likely to have cancer or ongoing scarring during an average of 4.7 years of follow-up.
 

Beyond topical steroids

“Almost always, topical steroids are all you need,” said Dr. Edwards. “Before I go beyond that, I think of other issues that may be causing symptoms,” such as atrophic vagina, steroid dermatitis, or vulvodynia.

For patients with refractory lichen sclerosus, other treatments “can add more oomph to your topical steroid, but they are not better,” she said.

Intralesional corticosteroid injections are one option.

Another option is adding a calcineurin inhibitor such as tacrolimus or pimecrolimus, although these medications can burn with application and irritate. In addition, they carry warnings about rare cases of cancer associated with their use.

Dr. Edwards also uses methotrexate, which is supported by case reports and an open-label study. In a recently published study that included 21 patients with vulvar lichen sclerosus and 24 patients with extragenital lichen sclerosus, about half improved after receiving methotrexate (Dermatol Ther. 2020 Apr 29;e13473.).
 

What about lasers?

Fractional CO₂ laser treatments, which are pulsed to minimize damage from heat, have “a lot of providers very excited,” Dr. Edwards said. In one open-label study of 40 patients, most reported a decrease in symptoms. (J Low Genit Tract Dis. 2020 Apr;24[2]:225-8.)

“We’re awaiting blinded, controlled studies,” Dr. Edwards said. “We don’t have those available yet although they are in progress.”

Ten of Dr. Edwards’ patients who did not improve enough with medication have received laser treatments. One patient stopped laser therapy after one treatment. One did not improve. Two were completely cleared, and six had significant improvement.

If patients who improved stopped steroids against recommendations, lichen sclerosus recurred, Dr. Edwards said.

The ISSVD does not recommend laser for the routine treatment of lichen sclerosus because of a lack of adequate studies and long-term safety data and biologic implausibility, Dr. Edwards noted (J Low Genit Tract Dis. 2019 Apr;23[2]:151-60.) Laser treatments for lichen sclerosus should not be used outside of clinical trials or without special arrangements for clinical governance, consent, and audit, according to a consensus document from the society.

“I mostly agree with that,” Dr. Edwards said. “But I now think that this is a reasonable thing to use when other treatments have been exhausted.”

Dr. Edwards and Dr. Venkatesan had no conflicts of interest. Dr. Haefner is an author for UpToDate.

[email protected]

Ultrapotent topical corticosteroids remain the core treatment for vulvar lichen sclerosus, although other therapies can be added, according to an expert speaking at the virtual conference on diseases of the vulva and vagina.

If needed, intralesional steroid injections or calcineurin inhibitors can be added to a topical corticosteroid regimen, Libby Edwards, MD, suggested at the meeting, hosted by the International Society for the Study of Vulvovaginal Disease. In addition, early reports indicate that newer interventions such as fractional CO₂ laser treatments may help patients with refractory disease.

Still, “there is no question, there is no argument: First-, second- and third-line treatment for lichen sclerosus is an ultrapotent or superpotent topical corticosteroid,” she said. Steroids include halobetasol, clobetasol, or betamethasone dipropionate in augmented vehicle ointment once or twice per day. Patients should continue this regimen until the skin texture is normal or the disease is controlled as well as possible, which usually takes several months, said Dr. Edwards, of Southeast Vulvar Clinic in Charlotte, N.C.

Patients then should continue treatment, but less frequently or with a lower potency steroid.

Although corticosteroids are not Food and Drug Administration–approved for the treatment of lichen sclerosus, double-blind, placebo-controlled trials support their use, Dr. Edwards said.

Getting patients to use topical corticosteroids as directed can be a challenge, however, and patient education is crucial.

After about 10 days, many patients start to feel better and stop the medication prematurely, which may lead to recurrence.

“That is such an important counseling point,” Aruna Venkatesan, MD, chief of dermatology and director of the genital dermatology clinic at Santa Clara Valley Medical Center in San Jose, Calif., said during a panel discussion. “Tell them, listen, I may not see you back for a couple months, and you may start feeling better sooner. But I want you to keep using this at this frequency so that when you come back we can make a good decision about whether you’re ready” for a lower potency regimen.

To encourage daily use, Hope K. Haefner, MD, asks patients whether they brush their teeth every night. “When they say yes, I tell them to put the steroid ointment by their toothpaste and use it after brushing,” Dr. Haefner, the Harold A. Furlong Professor of Women’s Health at Michigan Medicine in Ann Arbor, said during the discussion. “But don’t mix up the tubes.”

Once lichen sclerosus is controlled, options include decreasing the superpotent steroid to once, three times per week or changing to a midpotency steroid such as triamcinolone ointment every day, Dr. Edwards said.

Evidence suggests that controlling lichen sclerosus may prevent squamous cell carcinoma and scarring. In a study of more than 500 patients, about 70% complied with treatment instructions, whereas about 30% were considered partially compliant (JAMA Dermatol. 2015 Oct;151[10]:1061-7.). Patients who adhered to their therapy were less likely to have cancer or ongoing scarring during an average of 4.7 years of follow-up.
 

Beyond topical steroids

“Almost always, topical steroids are all you need,” said Dr. Edwards. “Before I go beyond that, I think of other issues that may be causing symptoms,” such as atrophic vagina, steroid dermatitis, or vulvodynia.

For patients with refractory lichen sclerosus, other treatments “can add more oomph to your topical steroid, but they are not better,” she said.

Intralesional corticosteroid injections are one option.

Another option is adding a calcineurin inhibitor such as tacrolimus or pimecrolimus, although these medications can burn with application and irritate. In addition, they carry warnings about rare cases of cancer associated with their use.

Dr. Edwards also uses methotrexate, which is supported by case reports and an open-label study. In a recently published study that included 21 patients with vulvar lichen sclerosus and 24 patients with extragenital lichen sclerosus, about half improved after receiving methotrexate (Dermatol Ther. 2020 Apr 29;e13473.).
 

What about lasers?

Fractional CO₂ laser treatments, which are pulsed to minimize damage from heat, have “a lot of providers very excited,” Dr. Edwards said. In one open-label study of 40 patients, most reported a decrease in symptoms. (J Low Genit Tract Dis. 2020 Apr;24[2]:225-8.)

“We’re awaiting blinded, controlled studies,” Dr. Edwards said. “We don’t have those available yet although they are in progress.”

Ten of Dr. Edwards’ patients who did not improve enough with medication have received laser treatments. One patient stopped laser therapy after one treatment. One did not improve. Two were completely cleared, and six had significant improvement.

If patients who improved stopped steroids against recommendations, lichen sclerosus recurred, Dr. Edwards said.

The ISSVD does not recommend laser for the routine treatment of lichen sclerosus because of a lack of adequate studies and long-term safety data and biologic implausibility, Dr. Edwards noted (J Low Genit Tract Dis. 2019 Apr;23[2]:151-60.) Laser treatments for lichen sclerosus should not be used outside of clinical trials or without special arrangements for clinical governance, consent, and audit, according to a consensus document from the society.

“I mostly agree with that,” Dr. Edwards said. “But I now think that this is a reasonable thing to use when other treatments have been exhausted.”

Dr. Edwards and Dr. Venkatesan had no conflicts of interest. Dr. Haefner is an author for UpToDate.

[email protected]

Ultrapotent topical corticosteroids remain the core treatment for vulvar lichen sclerosus, although other therapies can be added, according to an expert speaking at the virtual conference on diseases of the vulva and vagina.

If needed, intralesional steroid injections or calcineurin inhibitors can be added to a topical corticosteroid regimen, Libby Edwards, MD, suggested at the meeting, hosted by the International Society for the Study of Vulvovaginal Disease. In addition, early reports indicate that newer interventions such as fractional CO₂ laser treatments may help patients with refractory disease.

Still, “there is no question, there is no argument: First-, second- and third-line treatment for lichen sclerosus is an ultrapotent or superpotent topical corticosteroid,” she said. Steroids include halobetasol, clobetasol, or betamethasone dipropionate in augmented vehicle ointment once or twice per day. Patients should continue this regimen until the skin texture is normal or the disease is controlled as well as possible, which usually takes several months, said Dr. Edwards, of Southeast Vulvar Clinic in Charlotte, N.C.

Patients then should continue treatment, but less frequently or with a lower potency steroid.

Although corticosteroids are not Food and Drug Administration–approved for the treatment of lichen sclerosus, double-blind, placebo-controlled trials support their use, Dr. Edwards said.

Getting patients to use topical corticosteroids as directed can be a challenge, however, and patient education is crucial.

After about 10 days, many patients start to feel better and stop the medication prematurely, which may lead to recurrence.

“That is such an important counseling point,” Aruna Venkatesan, MD, chief of dermatology and director of the genital dermatology clinic at Santa Clara Valley Medical Center in San Jose, Calif., said during a panel discussion. “Tell them, listen, I may not see you back for a couple months, and you may start feeling better sooner. But I want you to keep using this at this frequency so that when you come back we can make a good decision about whether you’re ready” for a lower potency regimen.

To encourage daily use, Hope K. Haefner, MD, asks patients whether they brush their teeth every night. “When they say yes, I tell them to put the steroid ointment by their toothpaste and use it after brushing,” Dr. Haefner, the Harold A. Furlong Professor of Women’s Health at Michigan Medicine in Ann Arbor, said during the discussion. “But don’t mix up the tubes.”

Once lichen sclerosus is controlled, options include decreasing the superpotent steroid to once, three times per week or changing to a midpotency steroid such as triamcinolone ointment every day, Dr. Edwards said.

Evidence suggests that controlling lichen sclerosus may prevent squamous cell carcinoma and scarring. In a study of more than 500 patients, about 70% complied with treatment instructions, whereas about 30% were considered partially compliant (JAMA Dermatol. 2015 Oct;151[10]:1061-7.). Patients who adhered to their therapy were less likely to have cancer or ongoing scarring during an average of 4.7 years of follow-up.
 

Beyond topical steroids

“Almost always, topical steroids are all you need,” said Dr. Edwards. “Before I go beyond that, I think of other issues that may be causing symptoms,” such as atrophic vagina, steroid dermatitis, or vulvodynia.

For patients with refractory lichen sclerosus, other treatments “can add more oomph to your topical steroid, but they are not better,” she said.

Intralesional corticosteroid injections are one option.

Another option is adding a calcineurin inhibitor such as tacrolimus or pimecrolimus, although these medications can burn with application and irritate. In addition, they carry warnings about rare cases of cancer associated with their use.

Dr. Edwards also uses methotrexate, which is supported by case reports and an open-label study. In a recently published study that included 21 patients with vulvar lichen sclerosus and 24 patients with extragenital lichen sclerosus, about half improved after receiving methotrexate (Dermatol Ther. 2020 Apr 29;e13473.).
 

What about lasers?

Fractional CO₂ laser treatments, which are pulsed to minimize damage from heat, have “a lot of providers very excited,” Dr. Edwards said. In one open-label study of 40 patients, most reported a decrease in symptoms. (J Low Genit Tract Dis. 2020 Apr;24[2]:225-8.)

“We’re awaiting blinded, controlled studies,” Dr. Edwards said. “We don’t have those available yet although they are in progress.”

Ten of Dr. Edwards’ patients who did not improve enough with medication have received laser treatments. One patient stopped laser therapy after one treatment. One did not improve. Two were completely cleared, and six had significant improvement.

If patients who improved stopped steroids against recommendations, lichen sclerosus recurred, Dr. Edwards said.

The ISSVD does not recommend laser for the routine treatment of lichen sclerosus because of a lack of adequate studies and long-term safety data and biologic implausibility, Dr. Edwards noted (J Low Genit Tract Dis. 2019 Apr;23[2]:151-60.) Laser treatments for lichen sclerosus should not be used outside of clinical trials or without special arrangements for clinical governance, consent, and audit, according to a consensus document from the society.

“I mostly agree with that,” Dr. Edwards said. “But I now think that this is a reasonable thing to use when other treatments have been exhausted.”

Dr. Edwards and Dr. Venkatesan had no conflicts of interest. Dr. Haefner is an author for UpToDate.

[email protected]

The 2019 systemic lupus erythematosus (SLE) classification criteria jointly developed by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) proved significantly better at detecting true positive cases of the disease in children and young adults than did the 1997 ACR criteria, according to results from a single-center, retrospective study.

However, the 2019 criteria, which were developed using cohorts of adult patients with SLE, were statistically no better than the 1997 ACR criteria at identifying those without the disease, first author Najla Aljaberi, MBBS, of the Cincinnati Children’s Hospital Medical Center, and colleagues reported in Arthritis Care & Research.

The 2019 criteria were especially good at correctly classifying SLE in non-White youths, but the two sets of criteria performed equally well among male and female youths with SLE and across age groups.

“Our study confirms superior sensitivity of the new criteria over the 1997-ACR criteria in youths with SLE. The difference in sensitivity estimates between the two criteria sets (2019-EULAR/ACR vs. 1997-ACR) may be explained by a higher weight being assigned to immunologic criteria, less strict hematologic criteria (not requiring >2 occurrences), and the inclusion of subjective features of arthritis. Notably, our estimates of the sensitivity of the 2019-EULAR/ACR criteria were similar to those reported from a Brazilian pediatric study by Fonseca et al. (87.7%) that also used physician diagnosis as reference standard,” the researchers wrote.

Dr. Aljaberi and colleagues reviewed electronic medical records of 112 patients with SLE aged 2-21 years and 105 controls aged 1-19 years at Cincinnati Children’s Hospital Medical Center during 2008-2019. Patients identified in the records at the center were considered to have SLE based on ICD-10 codes assigned by experienced pediatric rheumatologists. The control patients included 69 (66%) with juvenile dermatomyositis and 36 with juvenile scleroderma/systemic sclerosis, based on corresponding ICD-10 codes.

Among the SLE cases, 57% were White and 81% were female, while Whites represented 83% and females 71% of control patients. Young adults aged 18-21 years represented a minority of SLE cases (18%) and controls (7%).

The 2019 criteria had significantly higher sensitivity than did the 1997 criteria (85% vs. 72%, respectively; P = .023) but similar specificity (83% vs. 87%; P = .456). A total of 17 out of the 112 SLE cases failed to meet the 2019 criteria, 13 (76%) of whom were White. Overall, 31 SLE cases did not meet the 1997 criteria, but 15 of those fulfilled the 2019 criteria. While there was no statistically significant difference in the sensitivity of the 2019 criteria between non-White and White cases (92% vs. 80%, respectively; P = .08), the difference in sensitivity was significant with the 1997 criteria (83% vs. 64%; P < .02).

The 2019 criteria had similar sensitivity in males and females (86% vs. 81%, respectively), as well as specificity (81% vs. 87%). The 1997 criteria also provided similar sensitivity between males and females (71% vs. 76%) as well as specificity (85% vs. 90%).

In only four instances did SLE cases meet 2019 criteria before ICD-10 diagnosis of SLE, whereas in the other 108 cases the ICD-10 diagnosis coincided with reaching the threshold for meeting 2019 criteria.

There was no funding secured for the study, and the authors had no conflicts of interest to disclose.

[email protected]

SOURCE: Aljaberi N et al. Arthritis Care Res. 2020 Aug 25. doi: 10.1002/acr.24430.

The 2019 systemic lupus erythematosus (SLE) classification criteria jointly developed by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) proved significantly better at detecting true positive cases of the disease in children and young adults than did the 1997 ACR criteria, according to results from a single-center, retrospective study.

However, the 2019 criteria, which were developed using cohorts of adult patients with SLE, were statistically no better than the 1997 ACR criteria at identifying those without the disease, first author Najla Aljaberi, MBBS, of the Cincinnati Children’s Hospital Medical Center, and colleagues reported in Arthritis Care & Research.

The 2019 criteria were especially good at correctly classifying SLE in non-White youths, but the two sets of criteria performed equally well among male and female youths with SLE and across age groups.

“Our study confirms superior sensitivity of the new criteria over the 1997-ACR criteria in youths with SLE. The difference in sensitivity estimates between the two criteria sets (2019-EULAR/ACR vs. 1997-ACR) may be explained by a higher weight being assigned to immunologic criteria, less strict hematologic criteria (not requiring >2 occurrences), and the inclusion of subjective features of arthritis. Notably, our estimates of the sensitivity of the 2019-EULAR/ACR criteria were similar to those reported from a Brazilian pediatric study by Fonseca et al. (87.7%) that also used physician diagnosis as reference standard,” the researchers wrote.

Dr. Aljaberi and colleagues reviewed electronic medical records of 112 patients with SLE aged 2-21 years and 105 controls aged 1-19 years at Cincinnati Children’s Hospital Medical Center during 2008-2019. Patients identified in the records at the center were considered to have SLE based on ICD-10 codes assigned by experienced pediatric rheumatologists. The control patients included 69 (66%) with juvenile dermatomyositis and 36 with juvenile scleroderma/systemic sclerosis, based on corresponding ICD-10 codes.

Among the SLE cases, 57% were White and 81% were female, while Whites represented 83% and females 71% of control patients. Young adults aged 18-21 years represented a minority of SLE cases (18%) and controls (7%).

The 2019 criteria had significantly higher sensitivity than did the 1997 criteria (85% vs. 72%, respectively; P = .023) but similar specificity (83% vs. 87%; P = .456). A total of 17 out of the 112 SLE cases failed to meet the 2019 criteria, 13 (76%) of whom were White. Overall, 31 SLE cases did not meet the 1997 criteria, but 15 of those fulfilled the 2019 criteria. While there was no statistically significant difference in the sensitivity of the 2019 criteria between non-White and White cases (92% vs. 80%, respectively; P = .08), the difference in sensitivity was significant with the 1997 criteria (83% vs. 64%; P < .02).

The 2019 criteria had similar sensitivity in males and females (86% vs. 81%, respectively), as well as specificity (81% vs. 87%). The 1997 criteria also provided similar sensitivity between males and females (71% vs. 76%) as well as specificity (85% vs. 90%).

In only four instances did SLE cases meet 2019 criteria before ICD-10 diagnosis of SLE, whereas in the other 108 cases the ICD-10 diagnosis coincided with reaching the threshold for meeting 2019 criteria.

There was no funding secured for the study, and the authors had no conflicts of interest to disclose.

[email protected]

SOURCE: Aljaberi N et al. Arthritis Care Res. 2020 Aug 25. doi: 10.1002/acr.24430.

The 2019 systemic lupus erythematosus (SLE) classification criteria jointly developed by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) proved significantly better at detecting true positive cases of the disease in children and young adults than did the 1997 ACR criteria, according to results from a single-center, retrospective study.

However, the 2019 criteria, which were developed using cohorts of adult patients with SLE, were statistically no better than the 1997 ACR criteria at identifying those without the disease, first author Najla Aljaberi, MBBS, of the Cincinnati Children’s Hospital Medical Center, and colleagues reported in Arthritis Care & Research.

The 2019 criteria were especially good at correctly classifying SLE in non-White youths, but the two sets of criteria performed equally well among male and female youths with SLE and across age groups.

“Our study confirms superior sensitivity of the new criteria over the 1997-ACR criteria in youths with SLE. The difference in sensitivity estimates between the two criteria sets (2019-EULAR/ACR vs. 1997-ACR) may be explained by a higher weight being assigned to immunologic criteria, less strict hematologic criteria (not requiring >2 occurrences), and the inclusion of subjective features of arthritis. Notably, our estimates of the sensitivity of the 2019-EULAR/ACR criteria were similar to those reported from a Brazilian pediatric study by Fonseca et al. (87.7%) that also used physician diagnosis as reference standard,” the researchers wrote.

Dr. Aljaberi and colleagues reviewed electronic medical records of 112 patients with SLE aged 2-21 years and 105 controls aged 1-19 years at Cincinnati Children’s Hospital Medical Center during 2008-2019. Patients identified in the records at the center were considered to have SLE based on ICD-10 codes assigned by experienced pediatric rheumatologists. The control patients included 69 (66%) with juvenile dermatomyositis and 36 with juvenile scleroderma/systemic sclerosis, based on corresponding ICD-10 codes.

Among the SLE cases, 57% were White and 81% were female, while Whites represented 83% and females 71% of control patients. Young adults aged 18-21 years represented a minority of SLE cases (18%) and controls (7%).

The 2019 criteria had significantly higher sensitivity than did the 1997 criteria (85% vs. 72%, respectively; P = .023) but similar specificity (83% vs. 87%; P = .456). A total of 17 out of the 112 SLE cases failed to meet the 2019 criteria, 13 (76%) of whom were White. Overall, 31 SLE cases did not meet the 1997 criteria, but 15 of those fulfilled the 2019 criteria. While there was no statistically significant difference in the sensitivity of the 2019 criteria between non-White and White cases (92% vs. 80%, respectively; P = .08), the difference in sensitivity was significant with the 1997 criteria (83% vs. 64%; P < .02).

The 2019 criteria had similar sensitivity in males and females (86% vs. 81%, respectively), as well as specificity (81% vs. 87%). The 1997 criteria also provided similar sensitivity between males and females (71% vs. 76%) as well as specificity (85% vs. 90%).

In only four instances did SLE cases meet 2019 criteria before ICD-10 diagnosis of SLE, whereas in the other 108 cases the ICD-10 diagnosis coincided with reaching the threshold for meeting 2019 criteria.

There was no funding secured for the study, and the authors had no conflicts of interest to disclose.

[email protected]

SOURCE: Aljaberi N et al. Arthritis Care Res. 2020 Aug 25. doi: 10.1002/acr.24430.

A modern approach to hidradenitis suppurativa (HS) that incorporates such strategies as lasers, marsupialization, and metformin is built on a strategy individualized to the patient’s own description of their most challenging symptoms, according to an expert summary presented at the Skin of Color Update 2020.

“If your patient is only focused on the appearance of the lesions or the presence of sinus tracts, they might not think your treatment is working,” said Ginette A. Okoye, MD, professor and chair, department of dermatology, Howard University, Washington.

Instead, she advised working with patients to define priorities, allowing them to measure and appreciate improvement. The most difficult symptoms for one patient, such as pain or persistent abscess drainage, might not be the same for another.

There is a large array of treatment options for HS. These were once typically employed in stepwise manner, moving from steroids to hormonal therapies, antibiotics, and on to biologics and lasers, but Dr. Okoye reported that she layers on treatments, guided by patient priorities and responses. “Most of my patients are not on just one treatment at a time,” she said.

In addition to patient goals, her treatment choices are also influenced by the presence of comorbidities such as metabolic syndrome, polycystic ovarian syndrome (PCOS), or inflammatory bowel disease (IBD). For example, she reported she is more likely to include metformin among treatment options in patients with central obesity or insulin resistance, whereas she moves more quickly to a biologic for those with another systemic inflammatory disease such as IBD.

Although multiple factors appear to contribute to the symptoms of HS, the pathophysiology remains incompletely understood, but follicular occlusion is often “a primary inciting event,” Dr. Okoye said.

For this reason, laser hair removal can provide substantial benefit, she noted. Not only does it eliminate the occlusion, but the heat generated by the laser eliminates some of the pathogens, such as Porphyromonas gingivalis, associated with HS.

“Lasers work well for preventing new lesions from forming but also in making active lesions go away faster,” said Dr. Okoye, who relies on the Nd:YAG laser when treating this disease in darker skin. She has found lasers to be particularly effective in mild to moderate disease.

When using lasers, one challenge is third-party insurance, according to Dr. Okoye, who reported that she has tried repeatedly to convince payers that this treatment is medically indicated for HS, but claims have been routinely denied. As a result, she has had to significantly discount the cost of laser at her center in order to provide access to “a modality that actually works.”

Incision and drainage of inflamed painful lesions is a common intervention in HS, but Dr. Okoye discourages this approach. Because of the high recurrence rates, the benefits are temporary. Instead, she recommends an intralesional injection of triamcinolone acetonide diluted with equal amounts of lidocaine.

With this injection, “there is immediate pain relief followed by significant resolution of the inflammation,” she said. Because of the likelihood that patients seeking care in the emergency department for acutely inflamed lesions will receive surgical treatment, Dr. Okoye recommends offering patients urgent appointments for steroid injections when painful and inflamed lesions need immediate attention.

In contrast, marsupialization of abscesses or sinus tracts, often called deroofing, is associated with a relatively low risk of recurrence, can be done under local anesthesia in an office, and can lead to resolution of persistent nodules in patients with mild disease.

“This is an easy procedure that takes relatively little time,” advised Dr. Okoye, who provided CPT codes (10060 and 10061) that will provide reimbursement as long as procedural notes describe the rationale.

Metformin is an attractive adjunctive therapy for HS in patients with type 2 diabetes or features that suggest metabolic disturbances, such as central obesity, hypercholesterolemia, hypertension, or hypertriglyceridemia. It should also be considered in patients with PCOS because metformin decreases ovarian androgen production, she said.

When prescribing metformin in HS, which is an off-label indication, “I prefer the extended release formulation. It has a better profile in regard to gastrointestinal side effects and it can be taken once-daily,” Dr. Okoye said.

Citing a study that suggests patients with HS have even worse quality of life scores than do patients with diabetes, Dr. Okoye also emphasized the importance of psychosocial support and lifestyle modification as part of a holistic approach. With multiple manifestations of varying severity, individualizing therapy to control symptoms that the patient finds most bothersome is essential for optimizing patient well being.

Tien Viet Nguyen, MD, who practices dermatology and conducts clinical research in Bellevue, Wash., agrees that a comprehensive treatment program is needed. First author of a recent review article on HS, Dr. Nguyen agreed that common comorbidities like IBD, PCOS, and diabetes are accompanied frequently by a host of mental health and behavioral issues that contribute to impaired quality of life, such as depression, low self-esteem, sexual dysfunction, impaired sleep, and substance use disorders.

“Therefore, addressing these important comorbidities and quality of life issues with other health care professionals as a team is the best approach to improving health outcomes,” he said in an interview.

Dr. Nguyen also recently authored a chapter on quality of life issues associated with HS in the soon-to-be-published Comprehensive Guide to Hidradenitis Suppurativa (1st Edition, Dermatology Clinics). He agreed that optimal outcomes are achieved by an interdisciplinary team of health care providers who can address the sometimes independent but often interrelated comorbidities associated with this disorder.
 

Dr. Okoye has financial relationships with Pfizer and Unilver, but neither is relevant to this topic.

A modern approach to hidradenitis suppurativa (HS) that incorporates such strategies as lasers, marsupialization, and metformin is built on a strategy individualized to the patient’s own description of their most challenging symptoms, according to an expert summary presented at the Skin of Color Update 2020.

“If your patient is only focused on the appearance of the lesions or the presence of sinus tracts, they might not think your treatment is working,” said Ginette A. Okoye, MD, professor and chair, department of dermatology, Howard University, Washington.

Instead, she advised working with patients to define priorities, allowing them to measure and appreciate improvement. The most difficult symptoms for one patient, such as pain or persistent abscess drainage, might not be the same for another.

There is a large array of treatment options for HS. These were once typically employed in stepwise manner, moving from steroids to hormonal therapies, antibiotics, and on to biologics and lasers, but Dr. Okoye reported that she layers on treatments, guided by patient priorities and responses. “Most of my patients are not on just one treatment at a time,” she said.

In addition to patient goals, her treatment choices are also influenced by the presence of comorbidities such as metabolic syndrome, polycystic ovarian syndrome (PCOS), or inflammatory bowel disease (IBD). For example, she reported she is more likely to include metformin among treatment options in patients with central obesity or insulin resistance, whereas she moves more quickly to a biologic for those with another systemic inflammatory disease such as IBD.

Although multiple factors appear to contribute to the symptoms of HS, the pathophysiology remains incompletely understood, but follicular occlusion is often “a primary inciting event,” Dr. Okoye said.

For this reason, laser hair removal can provide substantial benefit, she noted. Not only does it eliminate the occlusion, but the heat generated by the laser eliminates some of the pathogens, such as Porphyromonas gingivalis, associated with HS.

“Lasers work well for preventing new lesions from forming but also in making active lesions go away faster,” said Dr. Okoye, who relies on the Nd:YAG laser when treating this disease in darker skin. She has found lasers to be particularly effective in mild to moderate disease.

When using lasers, one challenge is third-party insurance, according to Dr. Okoye, who reported that she has tried repeatedly to convince payers that this treatment is medically indicated for HS, but claims have been routinely denied. As a result, she has had to significantly discount the cost of laser at her center in order to provide access to “a modality that actually works.”

Incision and drainage of inflamed painful lesions is a common intervention in HS, but Dr. Okoye discourages this approach. Because of the high recurrence rates, the benefits are temporary. Instead, she recommends an intralesional injection of triamcinolone acetonide diluted with equal amounts of lidocaine.

With this injection, “there is immediate pain relief followed by significant resolution of the inflammation,” she said. Because of the likelihood that patients seeking care in the emergency department for acutely inflamed lesions will receive surgical treatment, Dr. Okoye recommends offering patients urgent appointments for steroid injections when painful and inflamed lesions need immediate attention.

In contrast, marsupialization of abscesses or sinus tracts, often called deroofing, is associated with a relatively low risk of recurrence, can be done under local anesthesia in an office, and can lead to resolution of persistent nodules in patients with mild disease.

“This is an easy procedure that takes relatively little time,” advised Dr. Okoye, who provided CPT codes (10060 and 10061) that will provide reimbursement as long as procedural notes describe the rationale.

Metformin is an attractive adjunctive therapy for HS in patients with type 2 diabetes or features that suggest metabolic disturbances, such as central obesity, hypercholesterolemia, hypertension, or hypertriglyceridemia. It should also be considered in patients with PCOS because metformin decreases ovarian androgen production, she said.

When prescribing metformin in HS, which is an off-label indication, “I prefer the extended release formulation. It has a better profile in regard to gastrointestinal side effects and it can be taken once-daily,” Dr. Okoye said.

Citing a study that suggests patients with HS have even worse quality of life scores than do patients with diabetes, Dr. Okoye also emphasized the importance of psychosocial support and lifestyle modification as part of a holistic approach. With multiple manifestations of varying severity, individualizing therapy to control symptoms that the patient finds most bothersome is essential for optimizing patient well being.

Tien Viet Nguyen, MD, who practices dermatology and conducts clinical research in Bellevue, Wash., agrees that a comprehensive treatment program is needed. First author of a recent review article on HS, Dr. Nguyen agreed that common comorbidities like IBD, PCOS, and diabetes are accompanied frequently by a host of mental health and behavioral issues that contribute to impaired quality of life, such as depression, low self-esteem, sexual dysfunction, impaired sleep, and substance use disorders.

“Therefore, addressing these important comorbidities and quality of life issues with other health care professionals as a team is the best approach to improving health outcomes,” he said in an interview.

Dr. Nguyen also recently authored a chapter on quality of life issues associated with HS in the soon-to-be-published Comprehensive Guide to Hidradenitis Suppurativa (1st Edition, Dermatology Clinics). He agreed that optimal outcomes are achieved by an interdisciplinary team of health care providers who can address the sometimes independent but often interrelated comorbidities associated with this disorder.
 

Dr. Okoye has financial relationships with Pfizer and Unilver, but neither is relevant to this topic.

A modern approach to hidradenitis suppurativa (HS) that incorporates such strategies as lasers, marsupialization, and metformin is built on a strategy individualized to the patient’s own description of their most challenging symptoms, according to an expert summary presented at the Skin of Color Update 2020.

“If your patient is only focused on the appearance of the lesions or the presence of sinus tracts, they might not think your treatment is working,” said Ginette A. Okoye, MD, professor and chair, department of dermatology, Howard University, Washington.

Instead, she advised working with patients to define priorities, allowing them to measure and appreciate improvement. The most difficult symptoms for one patient, such as pain or persistent abscess drainage, might not be the same for another.

There is a large array of treatment options for HS. These were once typically employed in stepwise manner, moving from steroids to hormonal therapies, antibiotics, and on to biologics and lasers, but Dr. Okoye reported that she layers on treatments, guided by patient priorities and responses. “Most of my patients are not on just one treatment at a time,” she said.

In addition to patient goals, her treatment choices are also influenced by the presence of comorbidities such as metabolic syndrome, polycystic ovarian syndrome (PCOS), or inflammatory bowel disease (IBD). For example, she reported she is more likely to include metformin among treatment options in patients with central obesity or insulin resistance, whereas she moves more quickly to a biologic for those with another systemic inflammatory disease such as IBD.

Although multiple factors appear to contribute to the symptoms of HS, the pathophysiology remains incompletely understood, but follicular occlusion is often “a primary inciting event,” Dr. Okoye said.

For this reason, laser hair removal can provide substantial benefit, she noted. Not only does it eliminate the occlusion, but the heat generated by the laser eliminates some of the pathogens, such as Porphyromonas gingivalis, associated with HS.

“Lasers work well for preventing new lesions from forming but also in making active lesions go away faster,” said Dr. Okoye, who relies on the Nd:YAG laser when treating this disease in darker skin. She has found lasers to be particularly effective in mild to moderate disease.

When using lasers, one challenge is third-party insurance, according to Dr. Okoye, who reported that she has tried repeatedly to convince payers that this treatment is medically indicated for HS, but claims have been routinely denied. As a result, she has had to significantly discount the cost of laser at her center in order to provide access to “a modality that actually works.”

Incision and drainage of inflamed painful lesions is a common intervention in HS, but Dr. Okoye discourages this approach. Because of the high recurrence rates, the benefits are temporary. Instead, she recommends an intralesional injection of triamcinolone acetonide diluted with equal amounts of lidocaine.

With this injection, “there is immediate pain relief followed by significant resolution of the inflammation,” she said. Because of the likelihood that patients seeking care in the emergency department for acutely inflamed lesions will receive surgical treatment, Dr. Okoye recommends offering patients urgent appointments for steroid injections when painful and inflamed lesions need immediate attention.

In contrast, marsupialization of abscesses or sinus tracts, often called deroofing, is associated with a relatively low risk of recurrence, can be done under local anesthesia in an office, and can lead to resolution of persistent nodules in patients with mild disease.

“This is an easy procedure that takes relatively little time,” advised Dr. Okoye, who provided CPT codes (10060 and 10061) that will provide reimbursement as long as procedural notes describe the rationale.

Metformin is an attractive adjunctive therapy for HS in patients with type 2 diabetes or features that suggest metabolic disturbances, such as central obesity, hypercholesterolemia, hypertension, or hypertriglyceridemia. It should also be considered in patients with PCOS because metformin decreases ovarian androgen production, she said.

When prescribing metformin in HS, which is an off-label indication, “I prefer the extended release formulation. It has a better profile in regard to gastrointestinal side effects and it can be taken once-daily,” Dr. Okoye said.

Citing a study that suggests patients with HS have even worse quality of life scores than do patients with diabetes, Dr. Okoye also emphasized the importance of psychosocial support and lifestyle modification as part of a holistic approach. With multiple manifestations of varying severity, individualizing therapy to control symptoms that the patient finds most bothersome is essential for optimizing patient well being.

Tien Viet Nguyen, MD, who practices dermatology and conducts clinical research in Bellevue, Wash., agrees that a comprehensive treatment program is needed. First author of a recent review article on HS, Dr. Nguyen agreed that common comorbidities like IBD, PCOS, and diabetes are accompanied frequently by a host of mental health and behavioral issues that contribute to impaired quality of life, such as depression, low self-esteem, sexual dysfunction, impaired sleep, and substance use disorders.

“Therefore, addressing these important comorbidities and quality of life issues with other health care professionals as a team is the best approach to improving health outcomes,” he said in an interview.

Dr. Nguyen also recently authored a chapter on quality of life issues associated with HS in the soon-to-be-published Comprehensive Guide to Hidradenitis Suppurativa (1st Edition, Dermatology Clinics). He agreed that optimal outcomes are achieved by an interdisciplinary team of health care providers who can address the sometimes independent but often interrelated comorbidities associated with this disorder.
 

Dr. Okoye has financial relationships with Pfizer and Unilver, but neither is relevant to this topic.

Large unilateral hyperpigmented patches on the trunk with onset around puberty are the hallmark of a Becker nevus, also more descriptively called pigmented hairy epidermal nevus.

Becker nevi are a form of epidermal nevus that usually occur on the upper back or chest. They most commonly develop during puberty when there are increasing circulating levels of androgens. (Becker nevus cells are androgen sensitive.) This is consistent with this patient’s history of the lesion developing in her teens when the lesions become hyperpigmented and noticeable. The localized androgen sensitivity also can lead to unilateral hypoplastic breast growth when it occurs on the chest in young women.

The lesions are more common in males than females and often have associated hypertrichosis. The etiology is not certain but is thought to be due to regional loss of heterozygosity during embryogenesis leading to the abnormally elevated levels of androgen receptors and increased androgen sensitivity in the basal keratinocytes and dermal fibroblasts.

Laser is the most effective therapy for the hyperpigmentation and for hypertrichosis when present. If a young woman with a Becker nevus has breast hypoplasia, spironolactone (an antiandrogen) has been helpful in restoring breast growth. For this patient, the hyperpigmented patch was asymptomatic and not troublesome, so she opted not to treat it.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

Large unilateral hyperpigmented patches on the trunk with onset around puberty are the hallmark of a Becker nevus, also more descriptively called pigmented hairy epidermal nevus.

Becker nevi are a form of epidermal nevus that usually occur on the upper back or chest. They most commonly develop during puberty when there are increasing circulating levels of androgens. (Becker nevus cells are androgen sensitive.) This is consistent with this patient’s history of the lesion developing in her teens when the lesions become hyperpigmented and noticeable. The localized androgen sensitivity also can lead to unilateral hypoplastic breast growth when it occurs on the chest in young women.

The lesions are more common in males than females and often have associated hypertrichosis. The etiology is not certain but is thought to be due to regional loss of heterozygosity during embryogenesis leading to the abnormally elevated levels of androgen receptors and increased androgen sensitivity in the basal keratinocytes and dermal fibroblasts.

Laser is the most effective therapy for the hyperpigmentation and for hypertrichosis when present. If a young woman with a Becker nevus has breast hypoplasia, spironolactone (an antiandrogen) has been helpful in restoring breast growth. For this patient, the hyperpigmented patch was asymptomatic and not troublesome, so she opted not to treat it.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

Large unilateral hyperpigmented patches on the trunk with onset around puberty are the hallmark of a Becker nevus, also more descriptively called pigmented hairy epidermal nevus.

Becker nevi are a form of epidermal nevus that usually occur on the upper back or chest. They most commonly develop during puberty when there are increasing circulating levels of androgens. (Becker nevus cells are androgen sensitive.) This is consistent with this patient’s history of the lesion developing in her teens when the lesions become hyperpigmented and noticeable. The localized androgen sensitivity also can lead to unilateral hypoplastic breast growth when it occurs on the chest in young women.

The lesions are more common in males than females and often have associated hypertrichosis. The etiology is not certain but is thought to be due to regional loss of heterozygosity during embryogenesis leading to the abnormally elevated levels of androgen receptors and increased androgen sensitivity in the basal keratinocytes and dermal fibroblasts.

Laser is the most effective therapy for the hyperpigmentation and for hypertrichosis when present. If a young woman with a Becker nevus has breast hypoplasia, spironolactone (an antiandrogen) has been helpful in restoring breast growth. For this patient, the hyperpigmented patch was asymptomatic and not troublesome, so she opted not to treat it.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

In the opinion of Lawrence F. Eichenfield, MD, recent advances in the medical treatment of acne make it “an exciting time” for treating patients with the condition.

During the virtual annual Masters of Aesthetics Symposium, he highlighted the following new acne treatment options:

• Trifarotene cream 0.005% (Aklief). This marks the first new retinoid indicated for acne in several decades. It is indicated for the topical treatment of acne vulgaris in patients 9 years of age and older and has been studied in acne of the face, chest, and back. “It’s nice to have in our armamentarium,” he said.
• Tazarotene lotion 0.045% (Arazlo). The 0.1% formulation of tazarotene is commonly used for acne, but it can cause skin irritation, dryness, and erythema. The new 0.045% formulation was developed in a three-dimensional mesh matrix, with ingredients from an oil-in-water emulsion. “This allows for graduated dosing on the skin without as much irritation,” said Dr. Eichenfield, who is chief of pediatric and adolescent dermatology at Rady Children’s Hospital, San Diego.
• Minocycline 4% topical foam (Amzeeq). This marks the first and only topical minocycline prescription treatment for acne. “Its hydrophobic composition allows for stable and efficient delivery of inherently unstable pharmaceutical ingredients,” he said. “There is no evidence of photosensitivity as you’d expect from a minocycline-based product, and there are low systemic levels compared with oral minocycline.”
• Clascoterone cream 1% (Winlevi). This first-in-class topical androgen receptor inhibitor has been approved for the treatment of acne in patients 12 years and older. It competes with dihydrotestosterone and selectively targets androgen receptors in sebocytes and hair papilla cells. “It has been studied on the face and trunk and has been shown to inhibit sebum production, reduce secretion of inflammatory cytokines, and inhibit inflammatory pathways,” said Dr. Eichenfield, who is also professor of dermatology and pediatrics at the University of California, San Diego.
• From a systemic standpoint, sarecycline, a new tetracycline class antibiotic, has been approved for the treatment of inflammatory lesions of nonnodular moderate to severe acne vulgaris in patients 9 years and older. The once-daily drug can be taken with or without food in a weight-based dose. “This medicine appears to have a narrow spectrum of antibacterial activity compared with other tetracyclines,” he said. “It may have less of a negative effect on gut microbiome than traditional oral antibiotics.”

As for integrating these new options into existing clinical practice, Dr. Eichenfield predicts that the general approach to acne treatment will remain the same. “We’ll have to wait to see where the topical androgens fit into the treatment algorithms,” he said. “Our goal is to minimize scarring, minimize disease, and to modulate the disease course.”

Dr. Eichenfield disclosed that he has been an investigator and/or consultant for Almirall, Cassiopea, Dermata, Foamix, Galderma, L’Oreal, and Ortho Dermatologics.

[email protected]

In the opinion of Lawrence F. Eichenfield, MD, recent advances in the medical treatment of acne make it “an exciting time” for treating patients with the condition.

During the virtual annual Masters of Aesthetics Symposium, he highlighted the following new acne treatment options:

• Trifarotene cream 0.005% (Aklief). This marks the first new retinoid indicated for acne in several decades. It is indicated for the topical treatment of acne vulgaris in patients 9 years of age and older and has been studied in acne of the face, chest, and back. “It’s nice to have in our armamentarium,” he said.
• Tazarotene lotion 0.045% (Arazlo). The 0.1% formulation of tazarotene is commonly used for acne, but it can cause skin irritation, dryness, and erythema. The new 0.045% formulation was developed in a three-dimensional mesh matrix, with ingredients from an oil-in-water emulsion. “This allows for graduated dosing on the skin without as much irritation,” said Dr. Eichenfield, who is chief of pediatric and adolescent dermatology at Rady Children’s Hospital, San Diego.
• Minocycline 4% topical foam (Amzeeq). This marks the first and only topical minocycline prescription treatment for acne. “Its hydrophobic composition allows for stable and efficient delivery of inherently unstable pharmaceutical ingredients,” he said. “There is no evidence of photosensitivity as you’d expect from a minocycline-based product, and there are low systemic levels compared with oral minocycline.”
• Clascoterone cream 1% (Winlevi). This first-in-class topical androgen receptor inhibitor has been approved for the treatment of acne in patients 12 years and older. It competes with dihydrotestosterone and selectively targets androgen receptors in sebocytes and hair papilla cells. “It has been studied on the face and trunk and has been shown to inhibit sebum production, reduce secretion of inflammatory cytokines, and inhibit inflammatory pathways,” said Dr. Eichenfield, who is also professor of dermatology and pediatrics at the University of California, San Diego.
• From a systemic standpoint, sarecycline, a new tetracycline class antibiotic, has been approved for the treatment of inflammatory lesions of nonnodular moderate to severe acne vulgaris in patients 9 years and older. The once-daily drug can be taken with or without food in a weight-based dose. “This medicine appears to have a narrow spectrum of antibacterial activity compared with other tetracyclines,” he said. “It may have less of a negative effect on gut microbiome than traditional oral antibiotics.”

As for integrating these new options into existing clinical practice, Dr. Eichenfield predicts that the general approach to acne treatment will remain the same. “We’ll have to wait to see where the topical androgens fit into the treatment algorithms,” he said. “Our goal is to minimize scarring, minimize disease, and to modulate the disease course.”

Dr. Eichenfield disclosed that he has been an investigator and/or consultant for Almirall, Cassiopea, Dermata, Foamix, Galderma, L’Oreal, and Ortho Dermatologics.

[email protected]

In the opinion of Lawrence F. Eichenfield, MD, recent advances in the medical treatment of acne make it “an exciting time” for treating patients with the condition.

During the virtual annual Masters of Aesthetics Symposium, he highlighted the following new acne treatment options:

• Trifarotene cream 0.005% (Aklief). This marks the first new retinoid indicated for acne in several decades. It is indicated for the topical treatment of acne vulgaris in patients 9 years of age and older and has been studied in acne of the face, chest, and back. “It’s nice to have in our armamentarium,” he said.
• Tazarotene lotion 0.045% (Arazlo). The 0.1% formulation of tazarotene is commonly used for acne, but it can cause skin irritation, dryness, and erythema. The new 0.045% formulation was developed in a three-dimensional mesh matrix, with ingredients from an oil-in-water emulsion. “This allows for graduated dosing on the skin without as much irritation,” said Dr. Eichenfield, who is chief of pediatric and adolescent dermatology at Rady Children’s Hospital, San Diego.
• Minocycline 4% topical foam (Amzeeq). This marks the first and only topical minocycline prescription treatment for acne. “Its hydrophobic composition allows for stable and efficient delivery of inherently unstable pharmaceutical ingredients,” he said. “There is no evidence of photosensitivity as you’d expect from a minocycline-based product, and there are low systemic levels compared with oral minocycline.”
• Clascoterone cream 1% (Winlevi). This first-in-class topical androgen receptor inhibitor has been approved for the treatment of acne in patients 12 years and older. It competes with dihydrotestosterone and selectively targets androgen receptors in sebocytes and hair papilla cells. “It has been studied on the face and trunk and has been shown to inhibit sebum production, reduce secretion of inflammatory cytokines, and inhibit inflammatory pathways,” said Dr. Eichenfield, who is also professor of dermatology and pediatrics at the University of California, San Diego.
• From a systemic standpoint, sarecycline, a new tetracycline class antibiotic, has been approved for the treatment of inflammatory lesions of nonnodular moderate to severe acne vulgaris in patients 9 years and older. The once-daily drug can be taken with or without food in a weight-based dose. “This medicine appears to have a narrow spectrum of antibacterial activity compared with other tetracyclines,” he said. “It may have less of a negative effect on gut microbiome than traditional oral antibiotics.”

As for integrating these new options into existing clinical practice, Dr. Eichenfield predicts that the general approach to acne treatment will remain the same. “We’ll have to wait to see where the topical androgens fit into the treatment algorithms,” he said. “Our goal is to minimize scarring, minimize disease, and to modulate the disease course.”

Dr. Eichenfield disclosed that he has been an investigator and/or consultant for Almirall, Cassiopea, Dermata, Foamix, Galderma, L’Oreal, and Ortho Dermatologics.

[email protected]

Latino patients participating in clinical trials of psoriasis treatments were found to have different patterns of disease and a lower level of quality of life, compared with White participants in the same studies, according to new data presented at the virtual Skin of Color Update 2020.

“Our findings demonstrate that, though White psoriasis patients may have higher severity in certain body regions such as the trunk, axilla, and groin areas, Latino psoriasis patients have a greater distribution of involvement, particularly in their upper limbs,” reported Alyssa G. Ashbaugh, a third-year medical student at the University of California, Irvine.

The study also found that psoriasis had a greater adverse impact on well-being, as measured with the Dermatology Life Quality Index (DLQI). At entry into the trials from which these patients were drawn, the higher DLQI score, significantly lower quality of life, was nearly two times higher (13.78 vs. 7.31; P = .01) among the Latino patients, compared with White patients.

This is not the first study to show a greater negative impact from psoriasis on Latinos than Whites, according to Ms. Ashbaugh. For example, Latinos had the worse quality of life at baseline by DLQI score than White, Asians, or Black participants in a trial of etanercept that enrolled more than 2000 patients.

In this retrospective chart review, patient characteristics were evaluated in all 21 Latino patients enrolled in psoriasis clinical trials at the University of California, Irvine, in a recent period. They were matched by age and gender to an equal number of White patients participating in the same trials.

The mean age at diagnosis of psoriasis was older in the Latino group than in the White population (42.4 vs. 35.6 years; P = .20), but the difference did not reach statistical significance. The proportion of patients with severe disease on investigator global assessment was also greater but not significantly different in the Latino group, compared with the White group, respectively (42.9% vs. 28.6%; P = .10).

However, differences in the patterns of disease did reach significance. This included a lower mean Psoriasis Assessment Severity Index score of the trunk, axilla, and groin in Latinos (4.74 vs. 9.73; P = .02). But compared with White participants, Latinos had a higher mean percentage of body surface area involvement in the upper limbs (4.78 vs. 1.85; P = .004) and a higher percentage of total body surface area involvement (20.50 vs. 10.03; P = .02).

“While White patients were found to have lived many more years with psoriasis, it is important for future studies to examine whether this is due to earlier onset or delayed diagnosis, given the fact that minorities are less likely to have access to a dermatologist,” reported Ms. Ashbaugh, who performed this work under the guidance of the senior author, Natasha Mesinkovska, MD, PhD, with the department of dermatology, University of California, Irvine.

Overall, the study suggested that body surface coverage and severity is not similarly distributed in Latinos relative to Whites. Although Ms. Ashbaugh conceded that the small sample size and retrospective design of this study are important limitations, she believes that her study, along with previously published studies that suggest psoriasis characteristics may differ meaningfully by race or ethnicity, raises issues that should be explored in future studies designed to confirm differences and whether those differences should affect management.

Other studies have suggested “there are notable differences in the presentation of psoriasis between racial and ethnic groups with the Latino population often presenting to physicians with more severe psoriasis and increased body surface area involvement,” Ms. Ashbaugh noted. Although this appears to be one of the first studies to examine psoriasis characteristics in Latinos relative to Whites, she believes this is an area ripe for further analysis.

Psoriasis “is not a rare occurrence” in non-White populations even if U.S. data suggest that the prevalence in “people of color is lower than that of psoriasis in the U.S. white population,” Amy McMichael, MD, chair of the department of dermatology, Wake Forest Baptist Medical Center, Winston-Salem, N.C., commented in an interview after the meeting. She agreed that it cannot be assumed that psoriasis in skin of color has the same manifestations or responds to treatment in the same way as in White patients.

“Studies have suggested that lesion thickness and, often, extent of disease can be worse in patients of color. Few studies to date have examined the efficacy of treatments and impact of disease in these populations,” she said.

One exception was a study Dr. McMichael and colleagues published last year on the efficacy and safety of the interleukin-17 receptor A antagonist brodalumab for psoriasis in patients of color. The study showed that Black, Latino, and Asian patients participating in the AMAGINE-2 and AMAGINE-3 trials achieved similar outcomes as White participants.

“We published this study because this is one of the first, if not the first, to have enough patients of color to actually draw conclusions about the efficacy of the biologic as well as the patient-reported outcomes,” she explained.

Like the author of the evaluation of Latino patients undertaken at the University of California, Irvine, Dr. McMichael said studies of psoriasis specific to patients of color are needed.

“We cannot assume all patients of color will have the same outcomes as their Caucasian counterparts. It is imperative to include those of color in future psoriasis treatment trials in order to determine the efficacy of new medications,” she added, specifically calling for collection of data on patient-reported outcomes.

Ms. Ashbaugh has no relevant financial relationships to disclose. Dr. McMichael’s disclosures included serving as an investigator and/or consultant for companies that included Allergan, Procter & Gamble, Johnson & Johnson, and Aclaris.

Latino patients participating in clinical trials of psoriasis treatments were found to have different patterns of disease and a lower level of quality of life, compared with White participants in the same studies, according to new data presented at the virtual Skin of Color Update 2020.

“Our findings demonstrate that, though White psoriasis patients may have higher severity in certain body regions such as the trunk, axilla, and groin areas, Latino psoriasis patients have a greater distribution of involvement, particularly in their upper limbs,” reported Alyssa G. Ashbaugh, a third-year medical student at the University of California, Irvine.

The study also found that psoriasis had a greater adverse impact on well-being, as measured with the Dermatology Life Quality Index (DLQI). At entry into the trials from which these patients were drawn, the higher DLQI score, significantly lower quality of life, was nearly two times higher (13.78 vs. 7.31; P = .01) among the Latino patients, compared with White patients.

This is not the first study to show a greater negative impact from psoriasis on Latinos than Whites, according to Ms. Ashbaugh. For example, Latinos had the worse quality of life at baseline by DLQI score than White, Asians, or Black participants in a trial of etanercept that enrolled more than 2000 patients.

In this retrospective chart review, patient characteristics were evaluated in all 21 Latino patients enrolled in psoriasis clinical trials at the University of California, Irvine, in a recent period. They were matched by age and gender to an equal number of White patients participating in the same trials.

The mean age at diagnosis of psoriasis was older in the Latino group than in the White population (42.4 vs. 35.6 years; P = .20), but the difference did not reach statistical significance. The proportion of patients with severe disease on investigator global assessment was also greater but not significantly different in the Latino group, compared with the White group, respectively (42.9% vs. 28.6%; P = .10).

However, differences in the patterns of disease did reach significance. This included a lower mean Psoriasis Assessment Severity Index score of the trunk, axilla, and groin in Latinos (4.74 vs. 9.73; P = .02). But compared with White participants, Latinos had a higher mean percentage of body surface area involvement in the upper limbs (4.78 vs. 1.85; P = .004) and a higher percentage of total body surface area involvement (20.50 vs. 10.03; P = .02).

“While White patients were found to have lived many more years with psoriasis, it is important for future studies to examine whether this is due to earlier onset or delayed diagnosis, given the fact that minorities are less likely to have access to a dermatologist,” reported Ms. Ashbaugh, who performed this work under the guidance of the senior author, Natasha Mesinkovska, MD, PhD, with the department of dermatology, University of California, Irvine.

Overall, the study suggested that body surface coverage and severity is not similarly distributed in Latinos relative to Whites. Although Ms. Ashbaugh conceded that the small sample size and retrospective design of this study are important limitations, she believes that her study, along with previously published studies that suggest psoriasis characteristics may differ meaningfully by race or ethnicity, raises issues that should be explored in future studies designed to confirm differences and whether those differences should affect management.

Other studies have suggested “there are notable differences in the presentation of psoriasis between racial and ethnic groups with the Latino population often presenting to physicians with more severe psoriasis and increased body surface area involvement,” Ms. Ashbaugh noted. Although this appears to be one of the first studies to examine psoriasis characteristics in Latinos relative to Whites, she believes this is an area ripe for further analysis.

Psoriasis “is not a rare occurrence” in non-White populations even if U.S. data suggest that the prevalence in “people of color is lower than that of psoriasis in the U.S. white population,” Amy McMichael, MD, chair of the department of dermatology, Wake Forest Baptist Medical Center, Winston-Salem, N.C., commented in an interview after the meeting. She agreed that it cannot be assumed that psoriasis in skin of color has the same manifestations or responds to treatment in the same way as in White patients.

“Studies have suggested that lesion thickness and, often, extent of disease can be worse in patients of color. Few studies to date have examined the efficacy of treatments and impact of disease in these populations,” she said.

One exception was a study Dr. McMichael and colleagues published last year on the efficacy and safety of the interleukin-17 receptor A antagonist brodalumab for psoriasis in patients of color. The study showed that Black, Latino, and Asian patients participating in the AMAGINE-2 and AMAGINE-3 trials achieved similar outcomes as White participants.

“We published this study because this is one of the first, if not the first, to have enough patients of color to actually draw conclusions about the efficacy of the biologic as well as the patient-reported outcomes,” she explained.

Like the author of the evaluation of Latino patients undertaken at the University of California, Irvine, Dr. McMichael said studies of psoriasis specific to patients of color are needed.

“We cannot assume all patients of color will have the same outcomes as their Caucasian counterparts. It is imperative to include those of color in future psoriasis treatment trials in order to determine the efficacy of new medications,” she added, specifically calling for collection of data on patient-reported outcomes.

Ms. Ashbaugh has no relevant financial relationships to disclose. Dr. McMichael’s disclosures included serving as an investigator and/or consultant for companies that included Allergan, Procter & Gamble, Johnson & Johnson, and Aclaris.

Latino patients participating in clinical trials of psoriasis treatments were found to have different patterns of disease and a lower level of quality of life, compared with White participants in the same studies, according to new data presented at the virtual Skin of Color Update 2020.

“Our findings demonstrate that, though White psoriasis patients may have higher severity in certain body regions such as the trunk, axilla, and groin areas, Latino psoriasis patients have a greater distribution of involvement, particularly in their upper limbs,” reported Alyssa G. Ashbaugh, a third-year medical student at the University of California, Irvine.

The study also found that psoriasis had a greater adverse impact on well-being, as measured with the Dermatology Life Quality Index (DLQI). At entry into the trials from which these patients were drawn, the higher DLQI score, significantly lower quality of life, was nearly two times higher (13.78 vs. 7.31; P = .01) among the Latino patients, compared with White patients.

This is not the first study to show a greater negative impact from psoriasis on Latinos than Whites, according to Ms. Ashbaugh. For example, Latinos had the worse quality of life at baseline by DLQI score than White, Asians, or Black participants in a trial of etanercept that enrolled more than 2000 patients.

In this retrospective chart review, patient characteristics were evaluated in all 21 Latino patients enrolled in psoriasis clinical trials at the University of California, Irvine, in a recent period. They were matched by age and gender to an equal number of White patients participating in the same trials.

The mean age at diagnosis of psoriasis was older in the Latino group than in the White population (42.4 vs. 35.6 years; P = .20), but the difference did not reach statistical significance. The proportion of patients with severe disease on investigator global assessment was also greater but not significantly different in the Latino group, compared with the White group, respectively (42.9% vs. 28.6%; P = .10).

However, differences in the patterns of disease did reach significance. This included a lower mean Psoriasis Assessment Severity Index score of the trunk, axilla, and groin in Latinos (4.74 vs. 9.73; P = .02). But compared with White participants, Latinos had a higher mean percentage of body surface area involvement in the upper limbs (4.78 vs. 1.85; P = .004) and a higher percentage of total body surface area involvement (20.50 vs. 10.03; P = .02).

“While White patients were found to have lived many more years with psoriasis, it is important for future studies to examine whether this is due to earlier onset or delayed diagnosis, given the fact that minorities are less likely to have access to a dermatologist,” reported Ms. Ashbaugh, who performed this work under the guidance of the senior author, Natasha Mesinkovska, MD, PhD, with the department of dermatology, University of California, Irvine.

Overall, the study suggested that body surface coverage and severity is not similarly distributed in Latinos relative to Whites. Although Ms. Ashbaugh conceded that the small sample size and retrospective design of this study are important limitations, she believes that her study, along with previously published studies that suggest psoriasis characteristics may differ meaningfully by race or ethnicity, raises issues that should be explored in future studies designed to confirm differences and whether those differences should affect management.

Other studies have suggested “there are notable differences in the presentation of psoriasis between racial and ethnic groups with the Latino population often presenting to physicians with more severe psoriasis and increased body surface area involvement,” Ms. Ashbaugh noted. Although this appears to be one of the first studies to examine psoriasis characteristics in Latinos relative to Whites, she believes this is an area ripe for further analysis.

Psoriasis “is not a rare occurrence” in non-White populations even if U.S. data suggest that the prevalence in “people of color is lower than that of psoriasis in the U.S. white population,” Amy McMichael, MD, chair of the department of dermatology, Wake Forest Baptist Medical Center, Winston-Salem, N.C., commented in an interview after the meeting. She agreed that it cannot be assumed that psoriasis in skin of color has the same manifestations or responds to treatment in the same way as in White patients.

“Studies have suggested that lesion thickness and, often, extent of disease can be worse in patients of color. Few studies to date have examined the efficacy of treatments and impact of disease in these populations,” she said.

One exception was a study Dr. McMichael and colleagues published last year on the efficacy and safety of the interleukin-17 receptor A antagonist brodalumab for psoriasis in patients of color. The study showed that Black, Latino, and Asian patients participating in the AMAGINE-2 and AMAGINE-3 trials achieved similar outcomes as White participants.

“We published this study because this is one of the first, if not the first, to have enough patients of color to actually draw conclusions about the efficacy of the biologic as well as the patient-reported outcomes,” she explained.

Like the author of the evaluation of Latino patients undertaken at the University of California, Irvine, Dr. McMichael said studies of psoriasis specific to patients of color are needed.

“We cannot assume all patients of color will have the same outcomes as their Caucasian counterparts. It is imperative to include those of color in future psoriasis treatment trials in order to determine the efficacy of new medications,” she added, specifically calling for collection of data on patient-reported outcomes.

Ms. Ashbaugh has no relevant financial relationships to disclose. Dr. McMichael’s disclosures included serving as an investigator and/or consultant for companies that included Allergan, Procter & Gamble, Johnson & Johnson, and Aclaris.

The adjuvanted recombinant zoster vaccine Shingrix appears to be effective in older adults with autoimmune diseases who are not receiving treatment regimens that suppress the immune system, according to a post hoc analysis of patients in two clinical trials.

jarun011/thinkstock

A two-dose regimen of Shingrix was effective in 90.5% of a subset of patients in two phase 3 clinical trials of adults who were aged at least 50 years, according to Alemnew F. Dagnew, MD, of GlaxoSmithKline and colleagues. The lowest rates of effectiveness with Shingrix, for patients aged between 70-79 years, was 84.4%, the researchers reported in Rheumatology.

The CDC recommends adults aged at least 50 years receive two doses of Shingrix to help prevent reoccurrence of herpes zoster, or Zostavax (zoster vaccine live) if adults are allergic to components of the Shingrix vaccine or have tested negative for varicella zoster virus immunity.

Dr. Dagnew and colleagues evaluated Shingrix in 983 patients who received two doses of Shingrix and 960 patients who received placebo from the ZOE-50 and ZOE-70 trials, where each dose was administered at least 2 months apart. The mean age of patients in both groups was 68.8 years in the Shingrix group and 69.4 years in the placebo group, and more than half of patients in both Shingrix (59.9%) and placebo groups (60.8%) were women. About 7% of the patients in two clinical trial had a pIMD.

At enrollment, the most common preexisting immune-mediated disorders (pIMDs) were psoriasis (215 patients taking Shingrix vs. 239 patients on placebo), spondyloarthropathy (109 patients taking Shingrix vs. 89 patients on placebo), rheumatoid arthritis (96 patients taking Shingrix vs. 94 patients on placebo), and celiac disease (41 patients taking Shingrix vs. 34 patients on placebo). Dr. Dagnew and colleagues examined the subgroup of patients with pIMDs for safety and vaccine efficacy, which was defined as not developing herpes zoster before the second dose.

Overall, the efficacy of Shingrix was 90.5% across all age groups (95% confidence interval, 73.5%-97.5%), with the group aged between 70-79 years having the lowest rate of effectiveness (95% CI, 30.8%-98.3%). The rate of severe adverse events was 14.6% in the Shingrix group and 11.7% in the placebo group between the first Shingrix dose and for up to 1 year after the second dose. The most common adverse events were infections and infestations as well as cardiac disorders. “Our data show a balance between study groups in the frequency and nature of SAEs, confirming the favorable safety profile of [Shingrix] in populations with pIMDs,” Dr. Dagnew and colleagues wrote.

The researchers acknowledged that the ZOE-50/70 studies were underpowered to detect the efficacy and safety of Shingrix in individuals with pIMDs but said that the large number of participants in the studies let them estimate efficacy and adverse events for this subgroup. They also noted there was no randomization of pIMDs at enrollment, even though pIMDs occurred at similar rates between Shingrix and placebo groups.

This study was funded by GlaxoSmithKline; the company helped with conducting and analyzing the study and also provided the costs associated with publishing it. Five authors reported being an employee of GlaxoSmithKline during the time the work was conducted, and four of the five own stock in the company. One author is now an employee of UCB. One author reported having served on the advisory boards for Merck Sharp & Dohme, GlaxoSmithKline, and Curevo.

SOURCE: Dagnew AF et al. Rheumatology. 2020 Sep 10. doi: 10.1093/rheumatology/keaa424.

The adjuvanted recombinant zoster vaccine Shingrix appears to be effective in older adults with autoimmune diseases who are not receiving treatment regimens that suppress the immune system, according to a post hoc analysis of patients in two clinical trials.

jarun011/thinkstock

A two-dose regimen of Shingrix was effective in 90.5% of a subset of patients in two phase 3 clinical trials of adults who were aged at least 50 years, according to Alemnew F. Dagnew, MD, of GlaxoSmithKline and colleagues. The lowest rates of effectiveness with Shingrix, for patients aged between 70-79 years, was 84.4%, the researchers reported in Rheumatology.

The CDC recommends adults aged at least 50 years receive two doses of Shingrix to help prevent reoccurrence of herpes zoster, or Zostavax (zoster vaccine live) if adults are allergic to components of the Shingrix vaccine or have tested negative for varicella zoster virus immunity.

Dr. Dagnew and colleagues evaluated Shingrix in 983 patients who received two doses of Shingrix and 960 patients who received placebo from the ZOE-50 and ZOE-70 trials, where each dose was administered at least 2 months apart. The mean age of patients in both groups was 68.8 years in the Shingrix group and 69.4 years in the placebo group, and more than half of patients in both Shingrix (59.9%) and placebo groups (60.8%) were women. About 7% of the patients in two clinical trial had a pIMD.

At enrollment, the most common preexisting immune-mediated disorders (pIMDs) were psoriasis (215 patients taking Shingrix vs. 239 patients on placebo), spondyloarthropathy (109 patients taking Shingrix vs. 89 patients on placebo), rheumatoid arthritis (96 patients taking Shingrix vs. 94 patients on placebo), and celiac disease (41 patients taking Shingrix vs. 34 patients on placebo). Dr. Dagnew and colleagues examined the subgroup of patients with pIMDs for safety and vaccine efficacy, which was defined as not developing herpes zoster before the second dose.

Overall, the efficacy of Shingrix was 90.5% across all age groups (95% confidence interval, 73.5%-97.5%), with the group aged between 70-79 years having the lowest rate of effectiveness (95% CI, 30.8%-98.3%). The rate of severe adverse events was 14.6% in the Shingrix group and 11.7% in the placebo group between the first Shingrix dose and for up to 1 year after the second dose. The most common adverse events were infections and infestations as well as cardiac disorders. “Our data show a balance between study groups in the frequency and nature of SAEs, confirming the favorable safety profile of [Shingrix] in populations with pIMDs,” Dr. Dagnew and colleagues wrote.

The researchers acknowledged that the ZOE-50/70 studies were underpowered to detect the efficacy and safety of Shingrix in individuals with pIMDs but said that the large number of participants in the studies let them estimate efficacy and adverse events for this subgroup. They also noted there was no randomization of pIMDs at enrollment, even though pIMDs occurred at similar rates between Shingrix and placebo groups.

This study was funded by GlaxoSmithKline; the company helped with conducting and analyzing the study and also provided the costs associated with publishing it. Five authors reported being an employee of GlaxoSmithKline during the time the work was conducted, and four of the five own stock in the company. One author is now an employee of UCB. One author reported having served on the advisory boards for Merck Sharp & Dohme, GlaxoSmithKline, and Curevo.

SOURCE: Dagnew AF et al. Rheumatology. 2020 Sep 10. doi: 10.1093/rheumatology/keaa424.

The adjuvanted recombinant zoster vaccine Shingrix appears to be effective in older adults with autoimmune diseases who are not receiving treatment regimens that suppress the immune system, according to a post hoc analysis of patients in two clinical trials.

jarun011/thinkstock

A two-dose regimen of Shingrix was effective in 90.5% of a subset of patients in two phase 3 clinical trials of adults who were aged at least 50 years, according to Alemnew F. Dagnew, MD, of GlaxoSmithKline and colleagues. The lowest rates of effectiveness with Shingrix, for patients aged between 70-79 years, was 84.4%, the researchers reported in Rheumatology.

The CDC recommends adults aged at least 50 years receive two doses of Shingrix to help prevent reoccurrence of herpes zoster, or Zostavax (zoster vaccine live) if adults are allergic to components of the Shingrix vaccine or have tested negative for varicella zoster virus immunity.

Dr. Dagnew and colleagues evaluated Shingrix in 983 patients who received two doses of Shingrix and 960 patients who received placebo from the ZOE-50 and ZOE-70 trials, where each dose was administered at least 2 months apart. The mean age of patients in both groups was 68.8 years in the Shingrix group and 69.4 years in the placebo group, and more than half of patients in both Shingrix (59.9%) and placebo groups (60.8%) were women. About 7% of the patients in two clinical trial had a pIMD.

At enrollment, the most common preexisting immune-mediated disorders (pIMDs) were psoriasis (215 patients taking Shingrix vs. 239 patients on placebo), spondyloarthropathy (109 patients taking Shingrix vs. 89 patients on placebo), rheumatoid arthritis (96 patients taking Shingrix vs. 94 patients on placebo), and celiac disease (41 patients taking Shingrix vs. 34 patients on placebo). Dr. Dagnew and colleagues examined the subgroup of patients with pIMDs for safety and vaccine efficacy, which was defined as not developing herpes zoster before the second dose.

Overall, the efficacy of Shingrix was 90.5% across all age groups (95% confidence interval, 73.5%-97.5%), with the group aged between 70-79 years having the lowest rate of effectiveness (95% CI, 30.8%-98.3%). The rate of severe adverse events was 14.6% in the Shingrix group and 11.7% in the placebo group between the first Shingrix dose and for up to 1 year after the second dose. The most common adverse events were infections and infestations as well as cardiac disorders. “Our data show a balance between study groups in the frequency and nature of SAEs, confirming the favorable safety profile of [Shingrix] in populations with pIMDs,” Dr. Dagnew and colleagues wrote.

The researchers acknowledged that the ZOE-50/70 studies were underpowered to detect the efficacy and safety of Shingrix in individuals with pIMDs but said that the large number of participants in the studies let them estimate efficacy and adverse events for this subgroup. They also noted there was no randomization of pIMDs at enrollment, even though pIMDs occurred at similar rates between Shingrix and placebo groups.

This study was funded by GlaxoSmithKline; the company helped with conducting and analyzing the study and also provided the costs associated with publishing it. Five authors reported being an employee of GlaxoSmithKline during the time the work was conducted, and four of the five own stock in the company. One author is now an employee of UCB. One author reported having served on the advisory boards for Merck Sharp & Dohme, GlaxoSmithKline, and Curevo.

SOURCE: Dagnew AF et al. Rheumatology. 2020 Sep 10. doi: 10.1093/rheumatology/keaa424.