The opioid addiction medications buprenorphine and methadone should not be withheld from patients who are taking benzodiazepines or other drugs that depress the central nervous system, the Food and Drug Administration advised in a safety alert posted Sept. 20.

The combined use of these medication-assisted treatment (MAT) drugs and central nervous system (CNS) depressants can lead to serious side effects. But the harm associated with opioid addiction that remains untreated usually outweighs those risks, the agency said. After reviewing this issue, the FDA said, it is requiring that this information be added to the drug labels of buprenorphine and methadone in addition to “recommendations for minimizing the use of [MAT] drugs and benzodiazepines together.”

[email protected]

The opioid addiction medications buprenorphine and methadone should not be withheld from patients who are taking benzodiazepines or other drugs that depress the central nervous system, the Food and Drug Administration advised in a safety alert posted Sept. 20.

The combined use of these medication-assisted treatment (MAT) drugs and central nervous system (CNS) depressants can lead to serious side effects. But the harm associated with opioid addiction that remains untreated usually outweighs those risks, the agency said. After reviewing this issue, the FDA said, it is requiring that this information be added to the drug labels of buprenorphine and methadone in addition to “recommendations for minimizing the use of [MAT] drugs and benzodiazepines together.”

[email protected]

The opioid addiction medications buprenorphine and methadone should not be withheld from patients who are taking benzodiazepines or other drugs that depress the central nervous system, the Food and Drug Administration advised in a safety alert posted Sept. 20.

The combined use of these medication-assisted treatment (MAT) drugs and central nervous system (CNS) depressants can lead to serious side effects. But the harm associated with opioid addiction that remains untreated usually outweighs those risks, the agency said. After reviewing this issue, the FDA said, it is requiring that this information be added to the drug labels of buprenorphine and methadone in addition to “recommendations for minimizing the use of [MAT] drugs and benzodiazepines together.”

[email protected]

DENVER – A treatment regimen for postmenopausal women with osteoporosis that started with teriparatide (TPTD) for 2 years and switched to denosumab (DMAB) improved their spine trabecular microarchitecture – a predictor of fracture risk independent of areal bone mineral density – in a new analysis of the DATA trial and its extension study, DATA-Switch.

On the other hand, the converse strategy of switching from denosumab to teriparatide resulted in a temporary decline in bone mineral density. “The observed transient decrease in bone density corresponds to extremely elevated bone formation and resorptions markers, suggesting that high bone turnover is a cause of the transient loss,” Joy Tsai, MD, an instructor in medicine at Massachusetts General Hospital, Boston, said in an interview at a poster session of the annual meeting of the American Society for Bone and Mineral Research.

DENVER – A treatment regimen for postmenopausal women with osteoporosis that started with teriparatide (TPTD) for 2 years and switched to denosumab (DMAB) improved their spine trabecular microarchitecture – a predictor of fracture risk independent of areal bone mineral density – in a new analysis of the DATA trial and its extension study, DATA-Switch.

On the other hand, the converse strategy of switching from denosumab to teriparatide resulted in a temporary decline in bone mineral density. “The observed transient decrease in bone density corresponds to extremely elevated bone formation and resorptions markers, suggesting that high bone turnover is a cause of the transient loss,” Joy Tsai, MD, an instructor in medicine at Massachusetts General Hospital, Boston, said in an interview at a poster session of the annual meeting of the American Society for Bone and Mineral Research.

DENVER – A treatment regimen for postmenopausal women with osteoporosis that started with teriparatide (TPTD) for 2 years and switched to denosumab (DMAB) improved their spine trabecular microarchitecture – a predictor of fracture risk independent of areal bone mineral density – in a new analysis of the DATA trial and its extension study, DATA-Switch.

On the other hand, the converse strategy of switching from denosumab to teriparatide resulted in a temporary decline in bone mineral density. “The observed transient decrease in bone density corresponds to extremely elevated bone formation and resorptions markers, suggesting that high bone turnover is a cause of the transient loss,” Joy Tsai, MD, an instructor in medicine at Massachusetts General Hospital, Boston, said in an interview at a poster session of the annual meeting of the American Society for Bone and Mineral Research.

MADRID – Flotetuzumab, a novel bispecific monoclonal antibody that employs a proprietary technology to redirect T lymphocytes to kill CD123-expressing cells, was safe and demonstrated efficacy in patients with acute myeloid leukemia in a phase 1 trial, based on data presented at the European Society for Medical Oncology (ESMO) Congress.

Flotetuzumab combines a portion of antibody recognizing CD3, which is an activating molecule expressed by T cells, and an arm that recognizes CD123 on the cancer cell, explained Norbert Vey, MD, PhD, Head, Leukemia Treatment Unit, Institut Paoli-Calmettes, Marseille, France. This bispecific quality, produced through a proprietary technology called Dual-Affinity ReTargeting, is considered promising because CD123 is expressed by more than 90% of AML cells and is highly expressed on stem cells involved in initiating myelodysplastic syndrome (MDS).

In this dose-ranging study (NCT02152956), 42 patients with AML and 5 patients with MDS were treated in the first cycle with infusions of flotetuzumab on either a continuous 7-day or a 4-days-on, 3-days-off schedule. For subsequent cycles, patients received the 4-days-on, 3-days-off schedule. Continuous infusion is employed due to the short half-life of flotetuzumab.

The most common adverse events were infusion-related reactions, which were observed in 76.6% of patients. Pyrexia, a potential sign of cytokine release syndrome (CRS), was observed in 23.4% of patients, who were given tocilizumab at the earliest sign of CRS. Two patients had grade 3 CRS, and one discontinued therapy. There was also one case of grade 3 myalgia. Dr. Vey characterized the overall level of adverse events as “acceptable.”

In addition to its relative safety, flotetuzumab was associated with “encouraging antileukemic activity,” Dr. Vey said. Six of 14 patients receiving doses that exceeded 500 ng/kg per day had objective responses and two of these patients had complete responses. Again, toxicity at these dose levels was considered manageable.

“This rate of clinical response is exciting,” commented Tim Somervaille, MD, Senior Group Leader, Leukemia Biology Laboratory, Cancer Research UK Institute, Manchester (England). An ESMO-invited discussant on this paper, Dr. Somervaille expressed enthusiasm in general about a growing role for bispecific T-cell engagers. Blinatumomab, the first of these agents, received regulatory approval for refractory AML in 2014.

“There are a number of these bispecific T cell antibodies that are in early-phase trials,” said Dr. Somervaille, citing several that also target CD123 within the context of a different partner antigen than that employed by flotetuzumab. He also mentioned ongoing efforts to develop bispecific natural killer cell engagers that target malignant cells through immune activation.

As for flotetuzumab, the phase 1 trial provided adequate data to encourage further development.

“A cohort expansion is now ongoing and enrolling patients at 11 sites in the United States and Europe,” Dr. Vey reported. “A clinical update on these results is expected by the end of the year.”

Dr. Vey reported financial relationships with Bristol-Myers Squibb, Novartis, and Servier.

MacroGenics retains full development and commercialization rights to flotetuzumab in the United States, Canada, Mexico, Japan, South Korea, and India. Servier participates in the development and has rights to flotetuzumab in all other countries. The U.S. Food and Drug Administration has granted orphan drug designation to flotetuzumab for the investigational treatment of AML, according to a press release from MacroGenics.

MADRID – Flotetuzumab, a novel bispecific monoclonal antibody that employs a proprietary technology to redirect T lymphocytes to kill CD123-expressing cells, was safe and demonstrated efficacy in patients with acute myeloid leukemia in a phase 1 trial, based on data presented at the European Society for Medical Oncology (ESMO) Congress.

Flotetuzumab combines a portion of antibody recognizing CD3, which is an activating molecule expressed by T cells, and an arm that recognizes CD123 on the cancer cell, explained Norbert Vey, MD, PhD, Head, Leukemia Treatment Unit, Institut Paoli-Calmettes, Marseille, France. This bispecific quality, produced through a proprietary technology called Dual-Affinity ReTargeting, is considered promising because CD123 is expressed by more than 90% of AML cells and is highly expressed on stem cells involved in initiating myelodysplastic syndrome (MDS).

In this dose-ranging study (NCT02152956), 42 patients with AML and 5 patients with MDS were treated in the first cycle with infusions of flotetuzumab on either a continuous 7-day or a 4-days-on, 3-days-off schedule. For subsequent cycles, patients received the 4-days-on, 3-days-off schedule. Continuous infusion is employed due to the short half-life of flotetuzumab.

The most common adverse events were infusion-related reactions, which were observed in 76.6% of patients. Pyrexia, a potential sign of cytokine release syndrome (CRS), was observed in 23.4% of patients, who were given tocilizumab at the earliest sign of CRS. Two patients had grade 3 CRS, and one discontinued therapy. There was also one case of grade 3 myalgia. Dr. Vey characterized the overall level of adverse events as “acceptable.”

In addition to its relative safety, flotetuzumab was associated with “encouraging antileukemic activity,” Dr. Vey said. Six of 14 patients receiving doses that exceeded 500 ng/kg per day had objective responses and two of these patients had complete responses. Again, toxicity at these dose levels was considered manageable.

“This rate of clinical response is exciting,” commented Tim Somervaille, MD, Senior Group Leader, Leukemia Biology Laboratory, Cancer Research UK Institute, Manchester (England). An ESMO-invited discussant on this paper, Dr. Somervaille expressed enthusiasm in general about a growing role for bispecific T-cell engagers. Blinatumomab, the first of these agents, received regulatory approval for refractory AML in 2014.

“There are a number of these bispecific T cell antibodies that are in early-phase trials,” said Dr. Somervaille, citing several that also target CD123 within the context of a different partner antigen than that employed by flotetuzumab. He also mentioned ongoing efforts to develop bispecific natural killer cell engagers that target malignant cells through immune activation.

As for flotetuzumab, the phase 1 trial provided adequate data to encourage further development.

“A cohort expansion is now ongoing and enrolling patients at 11 sites in the United States and Europe,” Dr. Vey reported. “A clinical update on these results is expected by the end of the year.”

Dr. Vey reported financial relationships with Bristol-Myers Squibb, Novartis, and Servier.

MacroGenics retains full development and commercialization rights to flotetuzumab in the United States, Canada, Mexico, Japan, South Korea, and India. Servier participates in the development and has rights to flotetuzumab in all other countries. The U.S. Food and Drug Administration has granted orphan drug designation to flotetuzumab for the investigational treatment of AML, according to a press release from MacroGenics.

MADRID – Flotetuzumab, a novel bispecific monoclonal antibody that employs a proprietary technology to redirect T lymphocytes to kill CD123-expressing cells, was safe and demonstrated efficacy in patients with acute myeloid leukemia in a phase 1 trial, based on data presented at the European Society for Medical Oncology (ESMO) Congress.

Flotetuzumab combines a portion of antibody recognizing CD3, which is an activating molecule expressed by T cells, and an arm that recognizes CD123 on the cancer cell, explained Norbert Vey, MD, PhD, Head, Leukemia Treatment Unit, Institut Paoli-Calmettes, Marseille, France. This bispecific quality, produced through a proprietary technology called Dual-Affinity ReTargeting, is considered promising because CD123 is expressed by more than 90% of AML cells and is highly expressed on stem cells involved in initiating myelodysplastic syndrome (MDS).

In this dose-ranging study (NCT02152956), 42 patients with AML and 5 patients with MDS were treated in the first cycle with infusions of flotetuzumab on either a continuous 7-day or a 4-days-on, 3-days-off schedule. For subsequent cycles, patients received the 4-days-on, 3-days-off schedule. Continuous infusion is employed due to the short half-life of flotetuzumab.

The most common adverse events were infusion-related reactions, which were observed in 76.6% of patients. Pyrexia, a potential sign of cytokine release syndrome (CRS), was observed in 23.4% of patients, who were given tocilizumab at the earliest sign of CRS. Two patients had grade 3 CRS, and one discontinued therapy. There was also one case of grade 3 myalgia. Dr. Vey characterized the overall level of adverse events as “acceptable.”

In addition to its relative safety, flotetuzumab was associated with “encouraging antileukemic activity,” Dr. Vey said. Six of 14 patients receiving doses that exceeded 500 ng/kg per day had objective responses and two of these patients had complete responses. Again, toxicity at these dose levels was considered manageable.

“This rate of clinical response is exciting,” commented Tim Somervaille, MD, Senior Group Leader, Leukemia Biology Laboratory, Cancer Research UK Institute, Manchester (England). An ESMO-invited discussant on this paper, Dr. Somervaille expressed enthusiasm in general about a growing role for bispecific T-cell engagers. Blinatumomab, the first of these agents, received regulatory approval for refractory AML in 2014.

“There are a number of these bispecific T cell antibodies that are in early-phase trials,” said Dr. Somervaille, citing several that also target CD123 within the context of a different partner antigen than that employed by flotetuzumab. He also mentioned ongoing efforts to develop bispecific natural killer cell engagers that target malignant cells through immune activation.

As for flotetuzumab, the phase 1 trial provided adequate data to encourage further development.

“A cohort expansion is now ongoing and enrolling patients at 11 sites in the United States and Europe,” Dr. Vey reported. “A clinical update on these results is expected by the end of the year.”

Dr. Vey reported financial relationships with Bristol-Myers Squibb, Novartis, and Servier.

MacroGenics retains full development and commercialization rights to flotetuzumab in the United States, Canada, Mexico, Japan, South Korea, and India. Servier participates in the development and has rights to flotetuzumab in all other countries. The U.S. Food and Drug Administration has granted orphan drug designation to flotetuzumab for the investigational treatment of AML, according to a press release from MacroGenics.

AGA has issued a new clinical guideline on the role of therapeutic drug monitoring (TDM) in the management of IBD, published in the September 2017 issue of Gastroenterology. The guideline focuses on the application of TDM for biologic therapy, specifically anti–tumor necrosis factor-alpha (TNF) agents and thiopurines, and addresses questions about the risks and benefits of reactive TDM, routine proactive TDM, or no TDM in guiding treatment changes. AGA’s recommendations include:

AGA has issued a new clinical guideline on the role of therapeutic drug monitoring (TDM) in the management of IBD, published in the September 2017 issue of Gastroenterology. The guideline focuses on the application of TDM for biologic therapy, specifically anti–tumor necrosis factor-alpha (TNF) agents and thiopurines, and addresses questions about the risks and benefits of reactive TDM, routine proactive TDM, or no TDM in guiding treatment changes. AGA’s recommendations include:

AGA has issued a new clinical guideline on the role of therapeutic drug monitoring (TDM) in the management of IBD, published in the September 2017 issue of Gastroenterology. The guideline focuses on the application of TDM for biologic therapy, specifically anti–tumor necrosis factor-alpha (TNF) agents and thiopurines, and addresses questions about the risks and benefits of reactive TDM, routine proactive TDM, or no TDM in guiding treatment changes. AGA’s recommendations include:

Many breakthroughs have been achieved through gastroenterological and hepatological research over the past century, forming the basis of the modern medical practice. As the charitable arm of the American Gastroenterological Association (AGA), the AGA Research Foundation contributes to this tradition of discovery by providing a key source of funding at a critical juncture in a young researcher’s career.

“The Research Scholar Award will have a pivotal effect on my future career,” said Michael Dougan, MD, PhD, Massachusetts General Hospital, Boston, 2017 Research Scholar Award recipient. “This award enables me to establish my own research infrastructure, and lay the experimental foundations for my future work as a clinician‐scientist striving to understand the complex interplay between the immune system, metabolism, and cancer.”

[email protected]

Many breakthroughs have been achieved through gastroenterological and hepatological research over the past century, forming the basis of the modern medical practice. As the charitable arm of the American Gastroenterological Association (AGA), the AGA Research Foundation contributes to this tradition of discovery by providing a key source of funding at a critical juncture in a young researcher’s career.

“The Research Scholar Award will have a pivotal effect on my future career,” said Michael Dougan, MD, PhD, Massachusetts General Hospital, Boston, 2017 Research Scholar Award recipient. “This award enables me to establish my own research infrastructure, and lay the experimental foundations for my future work as a clinician‐scientist striving to understand the complex interplay between the immune system, metabolism, and cancer.”

[email protected]

Many breakthroughs have been achieved through gastroenterological and hepatological research over the past century, forming the basis of the modern medical practice. As the charitable arm of the American Gastroenterological Association (AGA), the AGA Research Foundation contributes to this tradition of discovery by providing a key source of funding at a critical juncture in a young researcher’s career.

“The Research Scholar Award will have a pivotal effect on my future career,” said Michael Dougan, MD, PhD, Massachusetts General Hospital, Boston, 2017 Research Scholar Award recipient. “This award enables me to establish my own research infrastructure, and lay the experimental foundations for my future work as a clinician‐scientist striving to understand the complex interplay between the immune system, metabolism, and cancer.”

[email protected]

BY AYAN KUSARI AND CATALINA MATIZ, MD

The patient was diagnosed with eruptive vellus hair cysts (EVHC). Treatment with a keratolytic, such as 12% lactic acid cream, was recommended. Hydrocortisone 2.5% once daily as needed also was recommended to treat the patient’s itch.

EVHC are benign middermal cysts characterized by epidermoid keratinization of the cyst wall, as well as lamellar keratin and vellus hairs within the cyst.¹ The term “eruptive vellus hair cysts” was first used to describe a longstanding hyperpigmented, monomorphous papular eruption in two children by Esterly, Fretzin, and Pinkus in 1977.² Clinically, EVHC present as 1- to 3-mm follicular, dome-shaped papules that are often skin-colored but also have been described as being brown, gray, green or black colored.^3,4 They appear suddenly and sometimes are associated with mild tenderness and pruritus.^1,5 EVHC most commonly present on the anterior chest but also can present on the upper and lower extremities, face, neck, axillae, and buttocks.⁴

Furthermore, although spontaneous resolution is possible through transepidermal elimination of cyst products, cases may persist for years in the absence of treatment.¹

Accurate diagnosis of eruptive vellus hair cysts is important to guide therapy.

Keratosis pilaris consists of follicular-based papules with variable erythema.⁴ It may be widespread – including over the anterior chest – but is most commonly seen on the cheeks, extensor surfaces of proximal upper extremities, and the anterior thighs.⁴ It is related to excessive keratinization, which leads to formation of horny plugs within hair-follicle orifices.¹

Steatocystoma multiplex is typically characterized by firm, yellow-to-flesh–colored dermal cysts ranging from a few millimeters to 1 cm in size.¹ They are sometimes clinically hard to distinguish from EVHC, and both are associated with keratin 17 gene mutations and type 2 pachyonychia congenita.¹ Nonetheless, this patient’s lesions did not have any features – such as size or drainage – that would point toward steatocystoma multiplex or other skin findings suggestive of pachyonychia congenita.

Superficial folliculitis, also known as Bockhart’s impetigo, is an infection of the follicular ostium and typically presents with perifollicular pustules on an erythematous base that may be painful or pruritic and can occur throughout the corpus, including the anterior trunk.¹

Acne vulgaris is a very common disease that involves the pilosebaceous unit and occurs most frequently on the face, back, upper arms, and chest. However, it is characterized by open and closed comedones, papules, and pustules and, in severe cases, nodules and cysts that may leave postinflammatory hyperpigmentation and scarring. Tiny, hyperpigmented, dome-shaped macules occurring exclusively on the chest would not be characteristic.

Patients with hypohidrotic ectodermal dysplasia, also known as Christ-Siemens-Touraine syndrome, can present with EVHC. This condition is characterized by a triad of fair, sparse short hair; hyperthermia related to decreased sweating; and missing teeth.⁴ Although EVHC have been reported in association with hypohidrotic ectodermal dysplasia, this patient does not have any of the dysmorphic features associated with this syndrome.¹¹

Patients with pachyonychia congenita (type 2) also may have EVHC as part of their presentation, but this patient does not have nail dystrophy, focal palmoplantar keratoderma, follicular keratoses, or multiple steatocysts which also are features of this condition.⁴

Treatment may be offered to patients who are distressed by the lesions or seek cosmesis. A 2012 review of 220 cases of EVHC found that topical retinoic acid, incision/excision, CO2 laser, erbium:yttrium-aluminum-garnet laser, needle evacuation, dermabrasion, and 10% urea cream were each associated with successful treatment in multiple cases.³

Forty years have passed since EVHC was identified as a distinct disease entity. Despite this, eruptive vellus hair cysts remains somewhat understudied, and further research is needed to determine an ideal treatment algorithm for patients with this condition. Our approach was to attempt noninvasive keratolytic therapy before considering retinoids or surgical options; we also recommended steroid treatment for symptom relief. Providers should keep EVHC in the differential for eruptions consisting of tiny papules so that appropriate treatment may be offered.

Dr. Matiz is a pediatric dermatologist at Rady Children’s Hospital, San Diego, and an assistant clinical professor in the department of pediatric and adolescent dermatology at the University of California, San Diego. Mr. Kusari is a medical student at the University of California, San Diego. Dr. Matiz and Mr. Kusari said they had no relevant financial disclosures.

Email them at [email protected].

References

1. “Dermatology.” 3rd ed. (Philadelphia: Saunders, 2012).

2. Arch Dermatol. 1977 Apr;113(4):500-3.

3. Am J Clin Dermatol. 2012 Feb 1;13(1):19-28.

4. “Hurwitz Clinical Pediatric Dermatology: A Textbook of Skin Disorders of Childhood and Adolescence.” 4th ed. (Philadelphia: Saunders, 2011).

5. Indian Dermatol Online J. 2013 Jul;4(3):213-5.

6. J Am Acad Dermatol. 1980 Oct;3(4):425-9.

7. Am J Dermatopathol. 1997 Jun;19(3):250-3.

8. Hum Mol Genet. 1998 Jul;7(7):1143-8.

9. Dermatology. 1998;196(4):392-6.

10. Arch Dermatol. 1986 Feb;122(2):141.

11. Int J Dermatol. 2001 Jun;40(6):401-2.

BY AYAN KUSARI AND CATALINA MATIZ, MD

The patient was diagnosed with eruptive vellus hair cysts (EVHC). Treatment with a keratolytic, such as 12% lactic acid cream, was recommended. Hydrocortisone 2.5% once daily as needed also was recommended to treat the patient’s itch.

EVHC are benign middermal cysts characterized by epidermoid keratinization of the cyst wall, as well as lamellar keratin and vellus hairs within the cyst.¹ The term “eruptive vellus hair cysts” was first used to describe a longstanding hyperpigmented, monomorphous papular eruption in two children by Esterly, Fretzin, and Pinkus in 1977.² Clinically, EVHC present as 1- to 3-mm follicular, dome-shaped papules that are often skin-colored but also have been described as being brown, gray, green or black colored.^3,4 They appear suddenly and sometimes are associated with mild tenderness and pruritus.^1,5 EVHC most commonly present on the anterior chest but also can present on the upper and lower extremities, face, neck, axillae, and buttocks.⁴

Furthermore, although spontaneous resolution is possible through transepidermal elimination of cyst products, cases may persist for years in the absence of treatment.¹

Accurate diagnosis of eruptive vellus hair cysts is important to guide therapy.

Keratosis pilaris consists of follicular-based papules with variable erythema.⁴ It may be widespread – including over the anterior chest – but is most commonly seen on the cheeks, extensor surfaces of proximal upper extremities, and the anterior thighs.⁴ It is related to excessive keratinization, which leads to formation of horny plugs within hair-follicle orifices.¹

Steatocystoma multiplex is typically characterized by firm, yellow-to-flesh–colored dermal cysts ranging from a few millimeters to 1 cm in size.¹ They are sometimes clinically hard to distinguish from EVHC, and both are associated with keratin 17 gene mutations and type 2 pachyonychia congenita.¹ Nonetheless, this patient’s lesions did not have any features – such as size or drainage – that would point toward steatocystoma multiplex or other skin findings suggestive of pachyonychia congenita.

Superficial folliculitis, also known as Bockhart’s impetigo, is an infection of the follicular ostium and typically presents with perifollicular pustules on an erythematous base that may be painful or pruritic and can occur throughout the corpus, including the anterior trunk.¹

Acne vulgaris is a very common disease that involves the pilosebaceous unit and occurs most frequently on the face, back, upper arms, and chest. However, it is characterized by open and closed comedones, papules, and pustules and, in severe cases, nodules and cysts that may leave postinflammatory hyperpigmentation and scarring. Tiny, hyperpigmented, dome-shaped macules occurring exclusively on the chest would not be characteristic.

Patients with hypohidrotic ectodermal dysplasia, also known as Christ-Siemens-Touraine syndrome, can present with EVHC. This condition is characterized by a triad of fair, sparse short hair; hyperthermia related to decreased sweating; and missing teeth.⁴ Although EVHC have been reported in association with hypohidrotic ectodermal dysplasia, this patient does not have any of the dysmorphic features associated with this syndrome.¹¹

Patients with pachyonychia congenita (type 2) also may have EVHC as part of their presentation, but this patient does not have nail dystrophy, focal palmoplantar keratoderma, follicular keratoses, or multiple steatocysts which also are features of this condition.⁴

Treatment may be offered to patients who are distressed by the lesions or seek cosmesis. A 2012 review of 220 cases of EVHC found that topical retinoic acid, incision/excision, CO2 laser, erbium:yttrium-aluminum-garnet laser, needle evacuation, dermabrasion, and 10% urea cream were each associated with successful treatment in multiple cases.³

Forty years have passed since EVHC was identified as a distinct disease entity. Despite this, eruptive vellus hair cysts remains somewhat understudied, and further research is needed to determine an ideal treatment algorithm for patients with this condition. Our approach was to attempt noninvasive keratolytic therapy before considering retinoids or surgical options; we also recommended steroid treatment for symptom relief. Providers should keep EVHC in the differential for eruptions consisting of tiny papules so that appropriate treatment may be offered.

Dr. Matiz is a pediatric dermatologist at Rady Children’s Hospital, San Diego, and an assistant clinical professor in the department of pediatric and adolescent dermatology at the University of California, San Diego. Mr. Kusari is a medical student at the University of California, San Diego. Dr. Matiz and Mr. Kusari said they had no relevant financial disclosures.

Email them at [email protected].

References

1. “Dermatology.” 3rd ed. (Philadelphia: Saunders, 2012).

2. Arch Dermatol. 1977 Apr;113(4):500-3.

3. Am J Clin Dermatol. 2012 Feb 1;13(1):19-28.

4. “Hurwitz Clinical Pediatric Dermatology: A Textbook of Skin Disorders of Childhood and Adolescence.” 4th ed. (Philadelphia: Saunders, 2011).

5. Indian Dermatol Online J. 2013 Jul;4(3):213-5.

6. J Am Acad Dermatol. 1980 Oct;3(4):425-9.

7. Am J Dermatopathol. 1997 Jun;19(3):250-3.

8. Hum Mol Genet. 1998 Jul;7(7):1143-8.

9. Dermatology. 1998;196(4):392-6.

10. Arch Dermatol. 1986 Feb;122(2):141.

11. Int J Dermatol. 2001 Jun;40(6):401-2.

BY AYAN KUSARI AND CATALINA MATIZ, MD

The patient was diagnosed with eruptive vellus hair cysts (EVHC). Treatment with a keratolytic, such as 12% lactic acid cream, was recommended. Hydrocortisone 2.5% once daily as needed also was recommended to treat the patient’s itch.

EVHC are benign middermal cysts characterized by epidermoid keratinization of the cyst wall, as well as lamellar keratin and vellus hairs within the cyst.¹ The term “eruptive vellus hair cysts” was first used to describe a longstanding hyperpigmented, monomorphous papular eruption in two children by Esterly, Fretzin, and Pinkus in 1977.² Clinically, EVHC present as 1- to 3-mm follicular, dome-shaped papules that are often skin-colored but also have been described as being brown, gray, green or black colored.^3,4 They appear suddenly and sometimes are associated with mild tenderness and pruritus.^1,5 EVHC most commonly present on the anterior chest but also can present on the upper and lower extremities, face, neck, axillae, and buttocks.⁴

Furthermore, although spontaneous resolution is possible through transepidermal elimination of cyst products, cases may persist for years in the absence of treatment.¹

Accurate diagnosis of eruptive vellus hair cysts is important to guide therapy.

Keratosis pilaris consists of follicular-based papules with variable erythema.⁴ It may be widespread – including over the anterior chest – but is most commonly seen on the cheeks, extensor surfaces of proximal upper extremities, and the anterior thighs.⁴ It is related to excessive keratinization, which leads to formation of horny plugs within hair-follicle orifices.¹

Steatocystoma multiplex is typically characterized by firm, yellow-to-flesh–colored dermal cysts ranging from a few millimeters to 1 cm in size.¹ They are sometimes clinically hard to distinguish from EVHC, and both are associated with keratin 17 gene mutations and type 2 pachyonychia congenita.¹ Nonetheless, this patient’s lesions did not have any features – such as size or drainage – that would point toward steatocystoma multiplex or other skin findings suggestive of pachyonychia congenita.

Superficial folliculitis, also known as Bockhart’s impetigo, is an infection of the follicular ostium and typically presents with perifollicular pustules on an erythematous base that may be painful or pruritic and can occur throughout the corpus, including the anterior trunk.¹

Acne vulgaris is a very common disease that involves the pilosebaceous unit and occurs most frequently on the face, back, upper arms, and chest. However, it is characterized by open and closed comedones, papules, and pustules and, in severe cases, nodules and cysts that may leave postinflammatory hyperpigmentation and scarring. Tiny, hyperpigmented, dome-shaped macules occurring exclusively on the chest would not be characteristic.

Patients with hypohidrotic ectodermal dysplasia, also known as Christ-Siemens-Touraine syndrome, can present with EVHC. This condition is characterized by a triad of fair, sparse short hair; hyperthermia related to decreased sweating; and missing teeth.⁴ Although EVHC have been reported in association with hypohidrotic ectodermal dysplasia, this patient does not have any of the dysmorphic features associated with this syndrome.¹¹

Patients with pachyonychia congenita (type 2) also may have EVHC as part of their presentation, but this patient does not have nail dystrophy, focal palmoplantar keratoderma, follicular keratoses, or multiple steatocysts which also are features of this condition.⁴

Treatment may be offered to patients who are distressed by the lesions or seek cosmesis. A 2012 review of 220 cases of EVHC found that topical retinoic acid, incision/excision, CO2 laser, erbium:yttrium-aluminum-garnet laser, needle evacuation, dermabrasion, and 10% urea cream were each associated with successful treatment in multiple cases.³

Forty years have passed since EVHC was identified as a distinct disease entity. Despite this, eruptive vellus hair cysts remains somewhat understudied, and further research is needed to determine an ideal treatment algorithm for patients with this condition. Our approach was to attempt noninvasive keratolytic therapy before considering retinoids or surgical options; we also recommended steroid treatment for symptom relief. Providers should keep EVHC in the differential for eruptions consisting of tiny papules so that appropriate treatment may be offered.

Dr. Matiz is a pediatric dermatologist at Rady Children’s Hospital, San Diego, and an assistant clinical professor in the department of pediatric and adolescent dermatology at the University of California, San Diego. Mr. Kusari is a medical student at the University of California, San Diego. Dr. Matiz and Mr. Kusari said they had no relevant financial disclosures.

Email them at [email protected].

References

1. “Dermatology.” 3rd ed. (Philadelphia: Saunders, 2012).

2. Arch Dermatol. 1977 Apr;113(4):500-3.

3. Am J Clin Dermatol. 2012 Feb 1;13(1):19-28.

4. “Hurwitz Clinical Pediatric Dermatology: A Textbook of Skin Disorders of Childhood and Adolescence.” 4th ed. (Philadelphia: Saunders, 2011).

5. Indian Dermatol Online J. 2013 Jul;4(3):213-5.

6. J Am Acad Dermatol. 1980 Oct;3(4):425-9.

7. Am J Dermatopathol. 1997 Jun;19(3):250-3.

8. Hum Mol Genet. 1998 Jul;7(7):1143-8.

9. Dermatology. 1998;196(4):392-6.

10. Arch Dermatol. 1986 Feb;122(2):141.

11. Int J Dermatol. 2001 Jun;40(6):401-2.

CMS released the Medicare Inpatient Prospective Payment System (IPPS) final rule, which affects hospital payments and includes provisions for ambulatory surgery centers (ASCs) and physician payments.

Thanks to the AGA members who submitted comments to the proposed rule, CMS withdrew plans to publicly post facility accreditation reviews and correction plans. Below is a summary of AGA’s position and where CMS landed on each issue.
 

1. Public display of final accreditation surveys and plans of correction.

Summary of AGA position – AGA urged CMS to withdraw its proposal making ASC accreditation surveys open to the public. To support shared transparency objectives, AGA recommended that if CMS were to finalize its proposal, the agency should first develop standards and a framework that considers both violation severity and scope.

CMS final rule – After consideration of the public comments received, CMS will not make ASC accreditation surveys open to the public. CMS was concerned that the suggestion to have accrediting organizations post their survey reports would appear as if it was attempting to circumvent current law, which prohibits CMS from disclosing survey reports or compelling the accrediting organizations to disclose the reports themselves.
 

2. EHR Incentive Program certification requirements for payment year 2018.

Summary of AGA position – AGA supported increased flexibility for 2018 and urged CMS to allow use of EHR technology certified to the 2014 software edition OR the 2015 software edition for the 2018 EHR Incentive Program.

CMS final rule – CMS will allow health care providers to use either 2014 or 2015 CEHRT or a combination of 2014 and 2015 CEHRT for the 2018 EHR Incentive Program.
 

3. Exception for ASC-based physicians under the EHR Incentive Program for payment years 2017 and 2018.

Summary of AGA position – AGA encouraged CMS to define ASC-based as a physician or other eligible professional who provides more than 50% of Medicare billed services in an ASC. AGA was concerned that implementing a higher threshold would leave certain physicians exposed to payment penalties, because the meaningful use requirement is set at 50% or more.

CMS final rule – Unfortunately, CMS set the definition of “ASC-based” as those who provide 75% of all services in an ASC, based on previous statutory definitions.

Policy changes are effective on Oct. 1, 2017, and changes to the 2017 and 2018 EHR Incentive Program apply immediately to the 2015 and 2016 reporting period, and provide relief that will impact 2017 and 2018 payments.
 

[email protected]

CMS released the Medicare Inpatient Prospective Payment System (IPPS) final rule, which affects hospital payments and includes provisions for ambulatory surgery centers (ASCs) and physician payments.

Thanks to the AGA members who submitted comments to the proposed rule, CMS withdrew plans to publicly post facility accreditation reviews and correction plans. Below is a summary of AGA’s position and where CMS landed on each issue.
 

1. Public display of final accreditation surveys and plans of correction.

Summary of AGA position – AGA urged CMS to withdraw its proposal making ASC accreditation surveys open to the public. To support shared transparency objectives, AGA recommended that if CMS were to finalize its proposal, the agency should first develop standards and a framework that considers both violation severity and scope.

CMS final rule – After consideration of the public comments received, CMS will not make ASC accreditation surveys open to the public. CMS was concerned that the suggestion to have accrediting organizations post their survey reports would appear as if it was attempting to circumvent current law, which prohibits CMS from disclosing survey reports or compelling the accrediting organizations to disclose the reports themselves.
 

2. EHR Incentive Program certification requirements for payment year 2018.

Summary of AGA position – AGA supported increased flexibility for 2018 and urged CMS to allow use of EHR technology certified to the 2014 software edition OR the 2015 software edition for the 2018 EHR Incentive Program.

CMS final rule – CMS will allow health care providers to use either 2014 or 2015 CEHRT or a combination of 2014 and 2015 CEHRT for the 2018 EHR Incentive Program.
 

3. Exception for ASC-based physicians under the EHR Incentive Program for payment years 2017 and 2018.

Summary of AGA position – AGA encouraged CMS to define ASC-based as a physician or other eligible professional who provides more than 50% of Medicare billed services in an ASC. AGA was concerned that implementing a higher threshold would leave certain physicians exposed to payment penalties, because the meaningful use requirement is set at 50% or more.

CMS final rule – Unfortunately, CMS set the definition of “ASC-based” as those who provide 75% of all services in an ASC, based on previous statutory definitions.

Policy changes are effective on Oct. 1, 2017, and changes to the 2017 and 2018 EHR Incentive Program apply immediately to the 2015 and 2016 reporting period, and provide relief that will impact 2017 and 2018 payments.
 

[email protected]

CMS released the Medicare Inpatient Prospective Payment System (IPPS) final rule, which affects hospital payments and includes provisions for ambulatory surgery centers (ASCs) and physician payments.

Thanks to the AGA members who submitted comments to the proposed rule, CMS withdrew plans to publicly post facility accreditation reviews and correction plans. Below is a summary of AGA’s position and where CMS landed on each issue.
 

1. Public display of final accreditation surveys and plans of correction.

Summary of AGA position – AGA urged CMS to withdraw its proposal making ASC accreditation surveys open to the public. To support shared transparency objectives, AGA recommended that if CMS were to finalize its proposal, the agency should first develop standards and a framework that considers both violation severity and scope.

CMS final rule – After consideration of the public comments received, CMS will not make ASC accreditation surveys open to the public. CMS was concerned that the suggestion to have accrediting organizations post their survey reports would appear as if it was attempting to circumvent current law, which prohibits CMS from disclosing survey reports or compelling the accrediting organizations to disclose the reports themselves.
 

2. EHR Incentive Program certification requirements for payment year 2018.

Summary of AGA position – AGA supported increased flexibility for 2018 and urged CMS to allow use of EHR technology certified to the 2014 software edition OR the 2015 software edition for the 2018 EHR Incentive Program.

CMS final rule – CMS will allow health care providers to use either 2014 or 2015 CEHRT or a combination of 2014 and 2015 CEHRT for the 2018 EHR Incentive Program.
 

3. Exception for ASC-based physicians under the EHR Incentive Program for payment years 2017 and 2018.

Summary of AGA position – AGA encouraged CMS to define ASC-based as a physician or other eligible professional who provides more than 50% of Medicare billed services in an ASC. AGA was concerned that implementing a higher threshold would leave certain physicians exposed to payment penalties, because the meaningful use requirement is set at 50% or more.

CMS final rule – Unfortunately, CMS set the definition of “ASC-based” as those who provide 75% of all services in an ASC, based on previous statutory definitions.

Policy changes are effective on Oct. 1, 2017, and changes to the 2017 and 2018 EHR Incentive Program apply immediately to the 2015 and 2016 reporting period, and provide relief that will impact 2017 and 2018 payments.
 

[email protected]

Following the stressful divorce of her parents, this 8-year-old girl’s hair began to fall out, prompting her referral to dermatology. Along with the hair loss, she has mild itching and burning in the area.

The child has a history of several atopic phenomena, including seasonal allergies, asthma, and eczema—all of which are replete in her family’s history.

EXAMINATION
The child is in no distress and is quite willing to show the affected area—a sizeable (10 x 8 cm), roughly round area of complete hair loss involving the nuchal periphery of her scalp. Fortunately, the area is covered by longer hair that drapes down.

No epidermal changes (ie, redness, scaling, edema) are seen, and no nodes are palpable in the area. Her arms, brows, and lashes appear normal after careful examination.

What is the diagnosis?

However, the real significance of ophiasis is its uncertain prognosis. For this patient, the extent and type of hair loss, her young age, and her atopic history all predict a poor prognosis. The hair loss is likely to be slow to resolve, if it does at all. It could progress to loss of all scalp hair (alopecia totalis) or every hair on her body (alopecia universalis).

Compounding the problem is the fact that no good treatment exists for this autoimmune disease, which affects those with genetic predisposition. Topical steroid application or intralesional steroid injections (3 to 5 mg/cc triamcinolone suspension) can promote the growth of a few hairs, but neither have an effect on the ultimate outcome. There have been reports of benefit from injectable biologics and oral antimalarials, but these medications have not been approved for use in AA.

Histopathologic studies with special stains show a lymphocytic infiltrate surrounding the hair follicle that prevents the growth of new hairs. Glucocorticoids (eg, prednisone) resolve this and allow new hair growth, but the treatment must be continued for months with unjustifiable adverse effects. Even then, full resolution must come on its own.

This patient was treated with a month-long course of topical triamcinolone 0.1% cream. But as stated above, her prognosis is somewhat guarded.

TAKE-HOME LEARNING POINTS

• Alopecia areata (AA) is an autoimmune process and a common cause of localized hair loss.
• This hair loss is usually acute, complete, and round, and is often seen in multiple patches.
• Of the many forms of AA, this one (ophiasis) has a less certain prognosis, worsened by youth, atopy, and lesion size.
• While ordinary AA resolves on its own in most cases, ophiasis can progress into total loss of scalp hair (alopecia totalis) or loss of all body hair (alopecia universalis).

Following the stressful divorce of her parents, this 8-year-old girl’s hair began to fall out, prompting her referral to dermatology. Along with the hair loss, she has mild itching and burning in the area.

The child has a history of several atopic phenomena, including seasonal allergies, asthma, and eczema—all of which are replete in her family’s history.

EXAMINATION
The child is in no distress and is quite willing to show the affected area—a sizeable (10 x 8 cm), roughly round area of complete hair loss involving the nuchal periphery of her scalp. Fortunately, the area is covered by longer hair that drapes down.

No epidermal changes (ie, redness, scaling, edema) are seen, and no nodes are palpable in the area. Her arms, brows, and lashes appear normal after careful examination.

What is the diagnosis?

However, the real significance of ophiasis is its uncertain prognosis. For this patient, the extent and type of hair loss, her young age, and her atopic history all predict a poor prognosis. The hair loss is likely to be slow to resolve, if it does at all. It could progress to loss of all scalp hair (alopecia totalis) or every hair on her body (alopecia universalis).

Compounding the problem is the fact that no good treatment exists for this autoimmune disease, which affects those with genetic predisposition. Topical steroid application or intralesional steroid injections (3 to 5 mg/cc triamcinolone suspension) can promote the growth of a few hairs, but neither have an effect on the ultimate outcome. There have been reports of benefit from injectable biologics and oral antimalarials, but these medications have not been approved for use in AA.

Histopathologic studies with special stains show a lymphocytic infiltrate surrounding the hair follicle that prevents the growth of new hairs. Glucocorticoids (eg, prednisone) resolve this and allow new hair growth, but the treatment must be continued for months with unjustifiable adverse effects. Even then, full resolution must come on its own.

This patient was treated with a month-long course of topical triamcinolone 0.1% cream. But as stated above, her prognosis is somewhat guarded.

TAKE-HOME LEARNING POINTS

• Alopecia areata (AA) is an autoimmune process and a common cause of localized hair loss.
• This hair loss is usually acute, complete, and round, and is often seen in multiple patches.
• Of the many forms of AA, this one (ophiasis) has a less certain prognosis, worsened by youth, atopy, and lesion size.
• While ordinary AA resolves on its own in most cases, ophiasis can progress into total loss of scalp hair (alopecia totalis) or loss of all body hair (alopecia universalis).

Following the stressful divorce of her parents, this 8-year-old girl’s hair began to fall out, prompting her referral to dermatology. Along with the hair loss, she has mild itching and burning in the area.

The child has a history of several atopic phenomena, including seasonal allergies, asthma, and eczema—all of which are replete in her family’s history.

EXAMINATION
The child is in no distress and is quite willing to show the affected area—a sizeable (10 x 8 cm), roughly round area of complete hair loss involving the nuchal periphery of her scalp. Fortunately, the area is covered by longer hair that drapes down.

No epidermal changes (ie, redness, scaling, edema) are seen, and no nodes are palpable in the area. Her arms, brows, and lashes appear normal after careful examination.

What is the diagnosis?

However, the real significance of ophiasis is its uncertain prognosis. For this patient, the extent and type of hair loss, her young age, and her atopic history all predict a poor prognosis. The hair loss is likely to be slow to resolve, if it does at all. It could progress to loss of all scalp hair (alopecia totalis) or every hair on her body (alopecia universalis).

Compounding the problem is the fact that no good treatment exists for this autoimmune disease, which affects those with genetic predisposition. Topical steroid application or intralesional steroid injections (3 to 5 mg/cc triamcinolone suspension) can promote the growth of a few hairs, but neither have an effect on the ultimate outcome. There have been reports of benefit from injectable biologics and oral antimalarials, but these medications have not been approved for use in AA.

Histopathologic studies with special stains show a lymphocytic infiltrate surrounding the hair follicle that prevents the growth of new hairs. Glucocorticoids (eg, prednisone) resolve this and allow new hair growth, but the treatment must be continued for months with unjustifiable adverse effects. Even then, full resolution must come on its own.

This patient was treated with a month-long course of topical triamcinolone 0.1% cream. But as stated above, her prognosis is somewhat guarded.

TAKE-HOME LEARNING POINTS

• Alopecia areata (AA) is an autoimmune process and a common cause of localized hair loss.
• This hair loss is usually acute, complete, and round, and is often seen in multiple patches.
• Of the many forms of AA, this one (ophiasis) has a less certain prognosis, worsened by youth, atopy, and lesion size.
• While ordinary AA resolves on its own in most cases, ophiasis can progress into total loss of scalp hair (alopecia totalis) or loss of all body hair (alopecia universalis).

SAN FRANCISCO – Blistering diseases are easily misdiagnosed and may resemble psoriasis or other conditions, but a routine histology and clinical examination aren’t sufficient diagnostic starting points.

“You have to have some kind of immunological test,” according to Peter Marinkovich, MD. “Pathologists will try to give you as much information as they can on the routine histology, but don’t use that as a diagnostic.”

If not properly identified, autoimmune blistering diseases can lead to chronic overexposure to steroids and resultant side effects without addressing the underlying problem, said Dr. Marinkovich of the department of dermatology at Stanford (Calif.) University.

Dr. Marinkovich gave one example of a patient who had been diagnosed with bullous pemphigoid several years before, and who was becoming Cushingoid as a result of steroids. But the diagnosis was made on the basis of histopathology and clinical appearance alone.

“Nobody had done the immunofluorescence test,” he explained at the annual meeting of the Pacific Dermatologic Association. “I did it, and it turned out she had linear IgA disease. The patient went through 2 years of toxicity just because nobody had done the immunofluorescence test.” Instead, the patient improved when placed on dapsone, which is much less toxic than prednisone.

Direct/indirect immunofluorescence is the highest-yield test for patients with blistering disease. “It’s the best way, I believe, to make the diagnosis,” Dr. Marinkovich said. If that test isn’t available, serum taken during an active phase can also be used. But serum samples can turn up false negatives, so dermatologists should consider collecting and testing serum samples several times.

Another useful tool is salt-split skin analysis, which will demarcate antigens to the roof or floor of the blister. Specifically, it helps distinguish bullous pemphigoid and epidermolysis bullosa acquisita.

In the future, Dr. Marinkovich said, ELISA (enzyme-linked immunosorbent assay) testing will have greater importance for diagnosis and disease monitoring, not just for pemphigus but for subepidermal bullous disorders as well.

Autoimmune blistering diseases do respond to prednisone treatment, although not as well as some other conditions. However, symptom improvement can mask the true cause of the disease.

“It’s easy for physicians to give steroids, and the patients will be happy for the time being; but that doesn’t solve the problem in the long term,” Dr. Marinkovich cautioned. “These are chronic conditions, and the patient will continue to require prednisone, and they’ll get more and more side effects, which could have been avoided if someone had done a more thorough investigation.”

Topical agents such as tetracycline, niacinamide, and topical steroids are more useful in pemphigoid than for pemphigus, because pemphigoid involves local immune factors that the agents can target, while pemphigus can be driven by antibodies alone, which are not as responsive to these treatments.

When systemic therapies are necessary, prednisone is a useful tool, but aim for the lowest possible dose, he said. Reducing prednisone dose is challenging in and of itself. Dropping the dose too quickly can lead to more long-term exposure, because a steep drop can lead to a rebound in the disease, which leads to a higher dose.

“The patient is on this roller coaster ride, up and down, up and down, and that alone can ramp up disease activity,” said Dr. Marinkovich. “Lowering steroid more steadily is a better way to go. This calms the disease down by itself.”

When steroids can’t be completely tapered, which is almost always the case in pemphigus and common in pemphigoid, add steroid-sparing agents such as mycophenolate and azathioprine.

If the steroid-sparing agents don’t get patients down to 10 mg/day prednisone or below, then consider using rituximab and intravenous IgG.

In Europe, physicians are using rituximab earlier in the course of disease, a strategy that appeared effective in a study published in the Lancet (2017 May 20;389[10083]:2031-40). “The evidence suggests to me that earlier use of rituximab tends to reduce the total amount of steroids that the patients are using and has the potential to reduce the duration of the disease,” Dr. Marinkovich said. “That’s a trend that will be going on in the next couple of years here in the United States.”

Dr. Marinkovich is an investigator on a clinical trial funded by Syntimmune.

SAN FRANCISCO – Blistering diseases are easily misdiagnosed and may resemble psoriasis or other conditions, but a routine histology and clinical examination aren’t sufficient diagnostic starting points.

“You have to have some kind of immunological test,” according to Peter Marinkovich, MD. “Pathologists will try to give you as much information as they can on the routine histology, but don’t use that as a diagnostic.”

If not properly identified, autoimmune blistering diseases can lead to chronic overexposure to steroids and resultant side effects without addressing the underlying problem, said Dr. Marinkovich of the department of dermatology at Stanford (Calif.) University.

Dr. Marinkovich gave one example of a patient who had been diagnosed with bullous pemphigoid several years before, and who was becoming Cushingoid as a result of steroids. But the diagnosis was made on the basis of histopathology and clinical appearance alone.

“Nobody had done the immunofluorescence test,” he explained at the annual meeting of the Pacific Dermatologic Association. “I did it, and it turned out she had linear IgA disease. The patient went through 2 years of toxicity just because nobody had done the immunofluorescence test.” Instead, the patient improved when placed on dapsone, which is much less toxic than prednisone.

Direct/indirect immunofluorescence is the highest-yield test for patients with blistering disease. “It’s the best way, I believe, to make the diagnosis,” Dr. Marinkovich said. If that test isn’t available, serum taken during an active phase can also be used. But serum samples can turn up false negatives, so dermatologists should consider collecting and testing serum samples several times.

Another useful tool is salt-split skin analysis, which will demarcate antigens to the roof or floor of the blister. Specifically, it helps distinguish bullous pemphigoid and epidermolysis bullosa acquisita.

In the future, Dr. Marinkovich said, ELISA (enzyme-linked immunosorbent assay) testing will have greater importance for diagnosis and disease monitoring, not just for pemphigus but for subepidermal bullous disorders as well.

Autoimmune blistering diseases do respond to prednisone treatment, although not as well as some other conditions. However, symptom improvement can mask the true cause of the disease.

“It’s easy for physicians to give steroids, and the patients will be happy for the time being; but that doesn’t solve the problem in the long term,” Dr. Marinkovich cautioned. “These are chronic conditions, and the patient will continue to require prednisone, and they’ll get more and more side effects, which could have been avoided if someone had done a more thorough investigation.”

Topical agents such as tetracycline, niacinamide, and topical steroids are more useful in pemphigoid than for pemphigus, because pemphigoid involves local immune factors that the agents can target, while pemphigus can be driven by antibodies alone, which are not as responsive to these treatments.

When systemic therapies are necessary, prednisone is a useful tool, but aim for the lowest possible dose, he said. Reducing prednisone dose is challenging in and of itself. Dropping the dose too quickly can lead to more long-term exposure, because a steep drop can lead to a rebound in the disease, which leads to a higher dose.

“The patient is on this roller coaster ride, up and down, up and down, and that alone can ramp up disease activity,” said Dr. Marinkovich. “Lowering steroid more steadily is a better way to go. This calms the disease down by itself.”

When steroids can’t be completely tapered, which is almost always the case in pemphigus and common in pemphigoid, add steroid-sparing agents such as mycophenolate and azathioprine.

If the steroid-sparing agents don’t get patients down to 10 mg/day prednisone or below, then consider using rituximab and intravenous IgG.

In Europe, physicians are using rituximab earlier in the course of disease, a strategy that appeared effective in a study published in the Lancet (2017 May 20;389[10083]:2031-40). “The evidence suggests to me that earlier use of rituximab tends to reduce the total amount of steroids that the patients are using and has the potential to reduce the duration of the disease,” Dr. Marinkovich said. “That’s a trend that will be going on in the next couple of years here in the United States.”

Dr. Marinkovich is an investigator on a clinical trial funded by Syntimmune.

SAN FRANCISCO – Blistering diseases are easily misdiagnosed and may resemble psoriasis or other conditions, but a routine histology and clinical examination aren’t sufficient diagnostic starting points.

“You have to have some kind of immunological test,” according to Peter Marinkovich, MD. “Pathologists will try to give you as much information as they can on the routine histology, but don’t use that as a diagnostic.”

If not properly identified, autoimmune blistering diseases can lead to chronic overexposure to steroids and resultant side effects without addressing the underlying problem, said Dr. Marinkovich of the department of dermatology at Stanford (Calif.) University.

Dr. Marinkovich gave one example of a patient who had been diagnosed with bullous pemphigoid several years before, and who was becoming Cushingoid as a result of steroids. But the diagnosis was made on the basis of histopathology and clinical appearance alone.

“Nobody had done the immunofluorescence test,” he explained at the annual meeting of the Pacific Dermatologic Association. “I did it, and it turned out she had linear IgA disease. The patient went through 2 years of toxicity just because nobody had done the immunofluorescence test.” Instead, the patient improved when placed on dapsone, which is much less toxic than prednisone.

Direct/indirect immunofluorescence is the highest-yield test for patients with blistering disease. “It’s the best way, I believe, to make the diagnosis,” Dr. Marinkovich said. If that test isn’t available, serum taken during an active phase can also be used. But serum samples can turn up false negatives, so dermatologists should consider collecting and testing serum samples several times.

Another useful tool is salt-split skin analysis, which will demarcate antigens to the roof or floor of the blister. Specifically, it helps distinguish bullous pemphigoid and epidermolysis bullosa acquisita.

In the future, Dr. Marinkovich said, ELISA (enzyme-linked immunosorbent assay) testing will have greater importance for diagnosis and disease monitoring, not just for pemphigus but for subepidermal bullous disorders as well.

Autoimmune blistering diseases do respond to prednisone treatment, although not as well as some other conditions. However, symptom improvement can mask the true cause of the disease.

“It’s easy for physicians to give steroids, and the patients will be happy for the time being; but that doesn’t solve the problem in the long term,” Dr. Marinkovich cautioned. “These are chronic conditions, and the patient will continue to require prednisone, and they’ll get more and more side effects, which could have been avoided if someone had done a more thorough investigation.”

Topical agents such as tetracycline, niacinamide, and topical steroids are more useful in pemphigoid than for pemphigus, because pemphigoid involves local immune factors that the agents can target, while pemphigus can be driven by antibodies alone, which are not as responsive to these treatments.

When systemic therapies are necessary, prednisone is a useful tool, but aim for the lowest possible dose, he said. Reducing prednisone dose is challenging in and of itself. Dropping the dose too quickly can lead to more long-term exposure, because a steep drop can lead to a rebound in the disease, which leads to a higher dose.

“The patient is on this roller coaster ride, up and down, up and down, and that alone can ramp up disease activity,” said Dr. Marinkovich. “Lowering steroid more steadily is a better way to go. This calms the disease down by itself.”

When steroids can’t be completely tapered, which is almost always the case in pemphigus and common in pemphigoid, add steroid-sparing agents such as mycophenolate and azathioprine.

If the steroid-sparing agents don’t get patients down to 10 mg/day prednisone or below, then consider using rituximab and intravenous IgG.

In Europe, physicians are using rituximab earlier in the course of disease, a strategy that appeared effective in a study published in the Lancet (2017 May 20;389[10083]:2031-40). “The evidence suggests to me that earlier use of rituximab tends to reduce the total amount of steroids that the patients are using and has the potential to reduce the duration of the disease,” Dr. Marinkovich said. “That’s a trend that will be going on in the next couple of years here in the United States.”

Dr. Marinkovich is an investigator on a clinical trial funded by Syntimmune.

The major improvement in survival that patients with systemic lupus erythematosus (SLE) have experienced from 1950 to the mid-1990s has plateaued ever since, reported Maria Tektonidou, MD, and her colleagues. The study was published in Annals of the Rheumatic Diseases.

Dr. Tektonidou of National and Kapodistrian University of Athens and her coauthors at the U.S. National Institute of Arthritis and Musculoskeletal and Skin Diseases performed a meta-analysis on studies examining survival in adult and pediatric SLE patients from the 1950s to the mid-1990s. Ultimately, they analyzed 125 adult studies, including 82 from high-income countries and 43 from low- to middle-income countries (LMIC), and 51 pediatric studies, of which 33 were from high-income countries and 18 from LMIC.

In adult studies, researchers found that both high-income and LMIC experienced gradual increases in survival from the 1950s to mid-1990s. After this period of time, the survival estimates stabilized. “In 2008–2016, the 5-year, 10-year, and 15-year survival estimates in high-income countries were 0.95 (95% credible interval, 0.94 to 0.96), 0.89 (0.88 to 0.90) and 0.82 (0.81 to 0.83), respectively” (Ann Rheum Dis. 2017 Aug 9. doi: 10.1136/annrheumdis-2017-211663).

Although there were no data for LMIC prior to 1970, researchers identified survival trends similar to those in high-income countries in more recent years. Over the same time period between 2008 and 2016, “the 5-year, 10-year, and 15-year survival estimates in LMIC were 0.92 (0.91 to 0.93), 0.85 (0.84 to 0.87) and 0.79 (0.78 to 0.81), respectively,” according to the report.

Unlike the steady improvement seen over a 40-year period with adult studies, pediatric SLE patients in high-income countries experienced dramatic increases in survival rates from the 1960s to the 1970s, followed by slower increases in survival rates. The researchers reported that between 2008 and 2016,“the 5-year and 10-year survival estimates from high-income countries were 0.99 (0.98 to 1.00) and 0.97 (0.96 to 0.98), respectively.”

LMIC had significantly worse survival in pediatric SLE patients than did their wealthy counterparts. “Survival persistently lagged [behind] that of high-income countries” between 1980 and 2000. Dr. Tektonidou and her associates found that “5-year and 10-year survival estimates from LMIC were 0.85 (0.83 to 0.88) and 0.79 (0.76 to 0.82), respectively.” Due to the small number of studies reporting 15-year survival rates, this time point was not included in the pediatric analysis.

The researchers also analyzed the cause of death for adult and pediatric SLE patients in both high-income countries and LMIC. High-income countries showed lower rates of SLE-associated deaths over time in adults, although infection-related deaths increased in adults in both high-income countries and LMIC. There were not enough studies and data to assess cause of death in pediatric studies in high-income countries, but pediatric patients in LMIC had an upward trend in SLE-associated deaths.

The Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases supported the study. The researchers reported having no relevant financial disclosures.

[email protected]

The major improvement in survival that patients with systemic lupus erythematosus (SLE) have experienced from 1950 to the mid-1990s has plateaued ever since, reported Maria Tektonidou, MD, and her colleagues. The study was published in Annals of the Rheumatic Diseases.

Dr. Tektonidou of National and Kapodistrian University of Athens and her coauthors at the U.S. National Institute of Arthritis and Musculoskeletal and Skin Diseases performed a meta-analysis on studies examining survival in adult and pediatric SLE patients from the 1950s to the mid-1990s. Ultimately, they analyzed 125 adult studies, including 82 from high-income countries and 43 from low- to middle-income countries (LMIC), and 51 pediatric studies, of which 33 were from high-income countries and 18 from LMIC.

In adult studies, researchers found that both high-income and LMIC experienced gradual increases in survival from the 1950s to mid-1990s. After this period of time, the survival estimates stabilized. “In 2008–2016, the 5-year, 10-year, and 15-year survival estimates in high-income countries were 0.95 (95% credible interval, 0.94 to 0.96), 0.89 (0.88 to 0.90) and 0.82 (0.81 to 0.83), respectively” (Ann Rheum Dis. 2017 Aug 9. doi: 10.1136/annrheumdis-2017-211663).

Although there were no data for LMIC prior to 1970, researchers identified survival trends similar to those in high-income countries in more recent years. Over the same time period between 2008 and 2016, “the 5-year, 10-year, and 15-year survival estimates in LMIC were 0.92 (0.91 to 0.93), 0.85 (0.84 to 0.87) and 0.79 (0.78 to 0.81), respectively,” according to the report.

Unlike the steady improvement seen over a 40-year period with adult studies, pediatric SLE patients in high-income countries experienced dramatic increases in survival rates from the 1960s to the 1970s, followed by slower increases in survival rates. The researchers reported that between 2008 and 2016,“the 5-year and 10-year survival estimates from high-income countries were 0.99 (0.98 to 1.00) and 0.97 (0.96 to 0.98), respectively.”

LMIC had significantly worse survival in pediatric SLE patients than did their wealthy counterparts. “Survival persistently lagged [behind] that of high-income countries” between 1980 and 2000. Dr. Tektonidou and her associates found that “5-year and 10-year survival estimates from LMIC were 0.85 (0.83 to 0.88) and 0.79 (0.76 to 0.82), respectively.” Due to the small number of studies reporting 15-year survival rates, this time point was not included in the pediatric analysis.

The researchers also analyzed the cause of death for adult and pediatric SLE patients in both high-income countries and LMIC. High-income countries showed lower rates of SLE-associated deaths over time in adults, although infection-related deaths increased in adults in both high-income countries and LMIC. There were not enough studies and data to assess cause of death in pediatric studies in high-income countries, but pediatric patients in LMIC had an upward trend in SLE-associated deaths.

The Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases supported the study. The researchers reported having no relevant financial disclosures.

[email protected]

The major improvement in survival that patients with systemic lupus erythematosus (SLE) have experienced from 1950 to the mid-1990s has plateaued ever since, reported Maria Tektonidou, MD, and her colleagues. The study was published in Annals of the Rheumatic Diseases.

Dr. Tektonidou of National and Kapodistrian University of Athens and her coauthors at the U.S. National Institute of Arthritis and Musculoskeletal and Skin Diseases performed a meta-analysis on studies examining survival in adult and pediatric SLE patients from the 1950s to the mid-1990s. Ultimately, they analyzed 125 adult studies, including 82 from high-income countries and 43 from low- to middle-income countries (LMIC), and 51 pediatric studies, of which 33 were from high-income countries and 18 from LMIC.

In adult studies, researchers found that both high-income and LMIC experienced gradual increases in survival from the 1950s to mid-1990s. After this period of time, the survival estimates stabilized. “In 2008–2016, the 5-year, 10-year, and 15-year survival estimates in high-income countries were 0.95 (95% credible interval, 0.94 to 0.96), 0.89 (0.88 to 0.90) and 0.82 (0.81 to 0.83), respectively” (Ann Rheum Dis. 2017 Aug 9. doi: 10.1136/annrheumdis-2017-211663).

Although there were no data for LMIC prior to 1970, researchers identified survival trends similar to those in high-income countries in more recent years. Over the same time period between 2008 and 2016, “the 5-year, 10-year, and 15-year survival estimates in LMIC were 0.92 (0.91 to 0.93), 0.85 (0.84 to 0.87) and 0.79 (0.78 to 0.81), respectively,” according to the report.

Unlike the steady improvement seen over a 40-year period with adult studies, pediatric SLE patients in high-income countries experienced dramatic increases in survival rates from the 1960s to the 1970s, followed by slower increases in survival rates. The researchers reported that between 2008 and 2016,“the 5-year and 10-year survival estimates from high-income countries were 0.99 (0.98 to 1.00) and 0.97 (0.96 to 0.98), respectively.”

LMIC had significantly worse survival in pediatric SLE patients than did their wealthy counterparts. “Survival persistently lagged [behind] that of high-income countries” between 1980 and 2000. Dr. Tektonidou and her associates found that “5-year and 10-year survival estimates from LMIC were 0.85 (0.83 to 0.88) and 0.79 (0.76 to 0.82), respectively.” Due to the small number of studies reporting 15-year survival rates, this time point was not included in the pediatric analysis.

The researchers also analyzed the cause of death for adult and pediatric SLE patients in both high-income countries and LMIC. High-income countries showed lower rates of SLE-associated deaths over time in adults, although infection-related deaths increased in adults in both high-income countries and LMIC. There were not enough studies and data to assess cause of death in pediatric studies in high-income countries, but pediatric patients in LMIC had an upward trend in SLE-associated deaths.

The Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases supported the study. The researchers reported having no relevant financial disclosures.

[email protected]