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New atopic dermatitis agents expand treatment options
GRAND CAYMAN, CAYMAN ISLANDS –
Moisturizers that confer skin barrier protection, lipid-replenishing topicals, and some biologics are available now or will soon be available for patients with AD, Joseph Fowler Jr., MD, said at the Caribbean Dermatology Symposium provided by Global Academy for Medical Education.
With the approval of dupilumab for moderate to severe disease in 2017, a biologic finally became available for treating AD, said Dr. Fowler of the University of Louisville (Ky.). While it’s not a cure and may take as long as 6 months to really kick in, “I think almost everyone gets some benefit from it. And although it’s not approved yet for anyone under 18, I’m sure it will be.”
He provided a brief rundown of dupilumab; crisaborole, another relatively new agent for AD; and some agents that are being investigated.
- Dupilumab. For AD, dupilumab, which inhibits interleukin-4 and interleukin-13 signaling, is usually started at 600 mg, then tapered to 300 mg subcutaneously every 2 weeks. Its pivotal data showed a mean 70% decrease in Eczema Area and Severity Index (EASI) scores over 16 weeks at that dose.*
“Again, I would say most patients do get benefit from this, but they might not see it for more than 3 months, and even up to 6 months. I’m not sure why, but some develop eye symptoms – I think these are more severe cases who also have respiratory atopy. I would also be interested to see if dupilumab might work on patients with chronic hand eczema,” he said.
- Crisaborole ointment 2%. A nonsteroidal topical phosphodiesterase 4 (PDE4) inhibitor approved in 2016 for mild to moderate AD in people aged 2 and older, crisaborole (Eucrisa) blocks the release of cyclic adenosine monophosphate (cAMP), which is elevated in AD. Lower cAMP levels lead to lower levels of inflammatory cytokines. In its pivotal phase 3 study, about 35% of patients achieved clinical success – an Investigator’s Static Global Assessment (ISGA) score of 0 or 1, or at least a two-grade improvement over baseline.
“In my opinion, it’s similar or slightly better than topical corticosteroids, and safer as well, especially in our younger patients, or when the face or intertriginous areas are involved,” Dr. Fowler said. “There is often some application site stinging and burning. If you put it in the fridge and get it good and cold when it goes on, that seems to moderate the sensation. It’s a good steroid-sparing option.”
Crisaborole is now being investigated for use in infants aged 3-24 months with mild to moderate AD.
- Tofacitinib ointment. This topical form of tofacitinib, an inhibitor of Janus kinase 1 and 3, is being evaluated in a placebo-controlled trial in adults with mild to moderate AD. There are also a few reports of oral tofacitinib improving AD, including a case report (Clin Exp Dermatol. 2017 Dec;42[8]:942-4). Dr. Fowler noted a small series of six adults with moderate to severe AD uncontrolled with methotrexate or azathioprine. The patients received oral tofacitinib 5 mg twice a day for 8-29 weeks; there was a mean 67% improvement in the Scoring Atopic Dermatitis (SCORAD) index.
- Ustekinumab. The interleukin-12 and -23 antagonist indicated for moderate to severe psoriasis has also made an appearance in the AD literature, including an Austrian report of three patients with severe AD who received 45 mg of ustekinumab (Stelara) subcutaneously at 0, 4 and 12 weeks. By week 16, all of them experienced a 50% reduction in their EASI score, with a marked reduction in interleukin-22 markers (J Am Acad Dermatol. 2017 Jan;76[1]:91-7.e3).
But no matter which therapy is chosen, regular moisturizing is critically important, Dr. Fowler remarked. Expensive prescription moisturizers are available, but he questioned whether they offer any cost-worthy extra benefit over a good nonprescription moisturizer.
“Do these super-moisturizers protect the skin barrier any more than petrolatum? I can’t answer that. They promise better results, but each patient and doc have to make the decision. If your patient can afford it, maybe some will be better for their skin, but really, it’s not as important as some of the other medications. So, I tell them, if cost is an issue, don’t worry about the fancy moisturizers.”
Dr. Fowler disclosed relationships with multiple pharmaceutical companies.
Global Academy and this news organization are owned by the same parent company.
Correction, 2/15/19: An earlier version of this article mischaracterized the chemical action of dupilumab.
GRAND CAYMAN, CAYMAN ISLANDS –
Moisturizers that confer skin barrier protection, lipid-replenishing topicals, and some biologics are available now or will soon be available for patients with AD, Joseph Fowler Jr., MD, said at the Caribbean Dermatology Symposium provided by Global Academy for Medical Education.
With the approval of dupilumab for moderate to severe disease in 2017, a biologic finally became available for treating AD, said Dr. Fowler of the University of Louisville (Ky.). While it’s not a cure and may take as long as 6 months to really kick in, “I think almost everyone gets some benefit from it. And although it’s not approved yet for anyone under 18, I’m sure it will be.”
He provided a brief rundown of dupilumab; crisaborole, another relatively new agent for AD; and some agents that are being investigated.
- Dupilumab. For AD, dupilumab, which inhibits interleukin-4 and interleukin-13 signaling, is usually started at 600 mg, then tapered to 300 mg subcutaneously every 2 weeks. Its pivotal data showed a mean 70% decrease in Eczema Area and Severity Index (EASI) scores over 16 weeks at that dose.*
“Again, I would say most patients do get benefit from this, but they might not see it for more than 3 months, and even up to 6 months. I’m not sure why, but some develop eye symptoms – I think these are more severe cases who also have respiratory atopy. I would also be interested to see if dupilumab might work on patients with chronic hand eczema,” he said.
- Crisaborole ointment 2%. A nonsteroidal topical phosphodiesterase 4 (PDE4) inhibitor approved in 2016 for mild to moderate AD in people aged 2 and older, crisaborole (Eucrisa) blocks the release of cyclic adenosine monophosphate (cAMP), which is elevated in AD. Lower cAMP levels lead to lower levels of inflammatory cytokines. In its pivotal phase 3 study, about 35% of patients achieved clinical success – an Investigator’s Static Global Assessment (ISGA) score of 0 or 1, or at least a two-grade improvement over baseline.
“In my opinion, it’s similar or slightly better than topical corticosteroids, and safer as well, especially in our younger patients, or when the face or intertriginous areas are involved,” Dr. Fowler said. “There is often some application site stinging and burning. If you put it in the fridge and get it good and cold when it goes on, that seems to moderate the sensation. It’s a good steroid-sparing option.”
Crisaborole is now being investigated for use in infants aged 3-24 months with mild to moderate AD.
- Tofacitinib ointment. This topical form of tofacitinib, an inhibitor of Janus kinase 1 and 3, is being evaluated in a placebo-controlled trial in adults with mild to moderate AD. There are also a few reports of oral tofacitinib improving AD, including a case report (Clin Exp Dermatol. 2017 Dec;42[8]:942-4). Dr. Fowler noted a small series of six adults with moderate to severe AD uncontrolled with methotrexate or azathioprine. The patients received oral tofacitinib 5 mg twice a day for 8-29 weeks; there was a mean 67% improvement in the Scoring Atopic Dermatitis (SCORAD) index.
- Ustekinumab. The interleukin-12 and -23 antagonist indicated for moderate to severe psoriasis has also made an appearance in the AD literature, including an Austrian report of three patients with severe AD who received 45 mg of ustekinumab (Stelara) subcutaneously at 0, 4 and 12 weeks. By week 16, all of them experienced a 50% reduction in their EASI score, with a marked reduction in interleukin-22 markers (J Am Acad Dermatol. 2017 Jan;76[1]:91-7.e3).
But no matter which therapy is chosen, regular moisturizing is critically important, Dr. Fowler remarked. Expensive prescription moisturizers are available, but he questioned whether they offer any cost-worthy extra benefit over a good nonprescription moisturizer.
“Do these super-moisturizers protect the skin barrier any more than petrolatum? I can’t answer that. They promise better results, but each patient and doc have to make the decision. If your patient can afford it, maybe some will be better for their skin, but really, it’s not as important as some of the other medications. So, I tell them, if cost is an issue, don’t worry about the fancy moisturizers.”
Dr. Fowler disclosed relationships with multiple pharmaceutical companies.
Global Academy and this news organization are owned by the same parent company.
Correction, 2/15/19: An earlier version of this article mischaracterized the chemical action of dupilumab.
GRAND CAYMAN, CAYMAN ISLANDS –
Moisturizers that confer skin barrier protection, lipid-replenishing topicals, and some biologics are available now or will soon be available for patients with AD, Joseph Fowler Jr., MD, said at the Caribbean Dermatology Symposium provided by Global Academy for Medical Education.
With the approval of dupilumab for moderate to severe disease in 2017, a biologic finally became available for treating AD, said Dr. Fowler of the University of Louisville (Ky.). While it’s not a cure and may take as long as 6 months to really kick in, “I think almost everyone gets some benefit from it. And although it’s not approved yet for anyone under 18, I’m sure it will be.”
He provided a brief rundown of dupilumab; crisaborole, another relatively new agent for AD; and some agents that are being investigated.
- Dupilumab. For AD, dupilumab, which inhibits interleukin-4 and interleukin-13 signaling, is usually started at 600 mg, then tapered to 300 mg subcutaneously every 2 weeks. Its pivotal data showed a mean 70% decrease in Eczema Area and Severity Index (EASI) scores over 16 weeks at that dose.*
“Again, I would say most patients do get benefit from this, but they might not see it for more than 3 months, and even up to 6 months. I’m not sure why, but some develop eye symptoms – I think these are more severe cases who also have respiratory atopy. I would also be interested to see if dupilumab might work on patients with chronic hand eczema,” he said.
- Crisaborole ointment 2%. A nonsteroidal topical phosphodiesterase 4 (PDE4) inhibitor approved in 2016 for mild to moderate AD in people aged 2 and older, crisaborole (Eucrisa) blocks the release of cyclic adenosine monophosphate (cAMP), which is elevated in AD. Lower cAMP levels lead to lower levels of inflammatory cytokines. In its pivotal phase 3 study, about 35% of patients achieved clinical success – an Investigator’s Static Global Assessment (ISGA) score of 0 or 1, or at least a two-grade improvement over baseline.
“In my opinion, it’s similar or slightly better than topical corticosteroids, and safer as well, especially in our younger patients, or when the face or intertriginous areas are involved,” Dr. Fowler said. “There is often some application site stinging and burning. If you put it in the fridge and get it good and cold when it goes on, that seems to moderate the sensation. It’s a good steroid-sparing option.”
Crisaborole is now being investigated for use in infants aged 3-24 months with mild to moderate AD.
- Tofacitinib ointment. This topical form of tofacitinib, an inhibitor of Janus kinase 1 and 3, is being evaluated in a placebo-controlled trial in adults with mild to moderate AD. There are also a few reports of oral tofacitinib improving AD, including a case report (Clin Exp Dermatol. 2017 Dec;42[8]:942-4). Dr. Fowler noted a small series of six adults with moderate to severe AD uncontrolled with methotrexate or azathioprine. The patients received oral tofacitinib 5 mg twice a day for 8-29 weeks; there was a mean 67% improvement in the Scoring Atopic Dermatitis (SCORAD) index.
- Ustekinumab. The interleukin-12 and -23 antagonist indicated for moderate to severe psoriasis has also made an appearance in the AD literature, including an Austrian report of three patients with severe AD who received 45 mg of ustekinumab (Stelara) subcutaneously at 0, 4 and 12 weeks. By week 16, all of them experienced a 50% reduction in their EASI score, with a marked reduction in interleukin-22 markers (J Am Acad Dermatol. 2017 Jan;76[1]:91-7.e3).
But no matter which therapy is chosen, regular moisturizing is critically important, Dr. Fowler remarked. Expensive prescription moisturizers are available, but he questioned whether they offer any cost-worthy extra benefit over a good nonprescription moisturizer.
“Do these super-moisturizers protect the skin barrier any more than petrolatum? I can’t answer that. They promise better results, but each patient and doc have to make the decision. If your patient can afford it, maybe some will be better for their skin, but really, it’s not as important as some of the other medications. So, I tell them, if cost is an issue, don’t worry about the fancy moisturizers.”
Dr. Fowler disclosed relationships with multiple pharmaceutical companies.
Global Academy and this news organization are owned by the same parent company.
Correction, 2/15/19: An earlier version of this article mischaracterized the chemical action of dupilumab.
REPORTING FROM THE CARIBBEAN DERMATOLOGY SYMPOSIUM
Hidradenitis suppurativa linked to increased lymphoma risk
Lymphomas appear to be up to four times more likely in patients with hidradenitis suppurativa than among the general population, Rachel Tannenbaum and her colleagues reported in a Research Letter in JAMA Dermatology.
The risks of Hodgkin (HL), non-Hodgkin (NHL), and cutaneous T-cell lymphoma (CTCL) all were significantly higher among patients with HS, wrote Ms. Tannenbaum, Andrew Strunk, and Amit Garg, MD. Males and older patients carried higher risks than females and younger patients, they found.
The team members, of Hofstra University, Hempstead, N.Y., conducted a health care database study comprising 55 million patients included in 27 integrated U.S. health care systems. All the subjects were at least 18 years old; records indicated active HS during the study period of 2013-2018. A regression analysis controlled for age and sex.
The database contained 62,690 patients with HS. The majority (74%) were female and were aged 44 years or younger (57%).
All three lymphomas were more common among HS patients than patients without HS, including non-Hodgkin lymphoma (0.40% vs. 0.35%,) Hodgkin lymphoma (0.17% vs. 0.09%), and cutaneous T-cell lymphoma (0.06% vs. 0.02%).
The multivariate analysis determined that HS patients were twice as likely to develop both non-Hodgkin and Hodgkin lymphoma (odds ratio, 2.0 and 2.21, respectively). They were four times more likely to develop cutaneous T-cell lymphoma (OR, 4.31).
All three lymphomas were more common among males than females: NHL, 0.62% vs. 0.32%; HL, 0.28% vs. 0.13%; and CTCL, 0.09% vs. 0.04%. This translated into significantly increased HS-associated risks, Ms. Tannenbaum and her coauthors noted. “For example, the [odds ratios] for the association between HS and HL were higher in males (OR, 2.97; 95% confidence interval, 2.22-3.99) than in females (OR, 1.86; 95% CI, 1.44-2.39) (P = .02),” they wrote.
Lymphomas were more common among HS patients in every age group. Patients with HS aged 45-64 years were 38% more likely to develop NHL, and those older than 65, about twice as likely (OR, 1.99).
“To our knowledge, this is the first investigation to systematically evaluate this association in a U.S. population of patients with HS,” the research team concluded.
The study was supported by a grant from AbbVie. Ms. Tannenbaum and Mr. Strunk reported no disclosures. Dr. Garg reported financial relationships with AbbVie and several other pharmaceutical companies.
SOURCE: Tannenbaum R et al. JAMA Dermatol. 2019 Jan 30. doi: 10.1001/jamadermatol.2018.5230.
Lymphomas appear to be up to four times more likely in patients with hidradenitis suppurativa than among the general population, Rachel Tannenbaum and her colleagues reported in a Research Letter in JAMA Dermatology.
The risks of Hodgkin (HL), non-Hodgkin (NHL), and cutaneous T-cell lymphoma (CTCL) all were significantly higher among patients with HS, wrote Ms. Tannenbaum, Andrew Strunk, and Amit Garg, MD. Males and older patients carried higher risks than females and younger patients, they found.
The team members, of Hofstra University, Hempstead, N.Y., conducted a health care database study comprising 55 million patients included in 27 integrated U.S. health care systems. All the subjects were at least 18 years old; records indicated active HS during the study period of 2013-2018. A regression analysis controlled for age and sex.
The database contained 62,690 patients with HS. The majority (74%) were female and were aged 44 years or younger (57%).
All three lymphomas were more common among HS patients than patients without HS, including non-Hodgkin lymphoma (0.40% vs. 0.35%,) Hodgkin lymphoma (0.17% vs. 0.09%), and cutaneous T-cell lymphoma (0.06% vs. 0.02%).
The multivariate analysis determined that HS patients were twice as likely to develop both non-Hodgkin and Hodgkin lymphoma (odds ratio, 2.0 and 2.21, respectively). They were four times more likely to develop cutaneous T-cell lymphoma (OR, 4.31).
All three lymphomas were more common among males than females: NHL, 0.62% vs. 0.32%; HL, 0.28% vs. 0.13%; and CTCL, 0.09% vs. 0.04%. This translated into significantly increased HS-associated risks, Ms. Tannenbaum and her coauthors noted. “For example, the [odds ratios] for the association between HS and HL were higher in males (OR, 2.97; 95% confidence interval, 2.22-3.99) than in females (OR, 1.86; 95% CI, 1.44-2.39) (P = .02),” they wrote.
Lymphomas were more common among HS patients in every age group. Patients with HS aged 45-64 years were 38% more likely to develop NHL, and those older than 65, about twice as likely (OR, 1.99).
“To our knowledge, this is the first investigation to systematically evaluate this association in a U.S. population of patients with HS,” the research team concluded.
The study was supported by a grant from AbbVie. Ms. Tannenbaum and Mr. Strunk reported no disclosures. Dr. Garg reported financial relationships with AbbVie and several other pharmaceutical companies.
SOURCE: Tannenbaum R et al. JAMA Dermatol. 2019 Jan 30. doi: 10.1001/jamadermatol.2018.5230.
Lymphomas appear to be up to four times more likely in patients with hidradenitis suppurativa than among the general population, Rachel Tannenbaum and her colleagues reported in a Research Letter in JAMA Dermatology.
The risks of Hodgkin (HL), non-Hodgkin (NHL), and cutaneous T-cell lymphoma (CTCL) all were significantly higher among patients with HS, wrote Ms. Tannenbaum, Andrew Strunk, and Amit Garg, MD. Males and older patients carried higher risks than females and younger patients, they found.
The team members, of Hofstra University, Hempstead, N.Y., conducted a health care database study comprising 55 million patients included in 27 integrated U.S. health care systems. All the subjects were at least 18 years old; records indicated active HS during the study period of 2013-2018. A regression analysis controlled for age and sex.
The database contained 62,690 patients with HS. The majority (74%) were female and were aged 44 years or younger (57%).
All three lymphomas were more common among HS patients than patients without HS, including non-Hodgkin lymphoma (0.40% vs. 0.35%,) Hodgkin lymphoma (0.17% vs. 0.09%), and cutaneous T-cell lymphoma (0.06% vs. 0.02%).
The multivariate analysis determined that HS patients were twice as likely to develop both non-Hodgkin and Hodgkin lymphoma (odds ratio, 2.0 and 2.21, respectively). They were four times more likely to develop cutaneous T-cell lymphoma (OR, 4.31).
All three lymphomas were more common among males than females: NHL, 0.62% vs. 0.32%; HL, 0.28% vs. 0.13%; and CTCL, 0.09% vs. 0.04%. This translated into significantly increased HS-associated risks, Ms. Tannenbaum and her coauthors noted. “For example, the [odds ratios] for the association between HS and HL were higher in males (OR, 2.97; 95% confidence interval, 2.22-3.99) than in females (OR, 1.86; 95% CI, 1.44-2.39) (P = .02),” they wrote.
Lymphomas were more common among HS patients in every age group. Patients with HS aged 45-64 years were 38% more likely to develop NHL, and those older than 65, about twice as likely (OR, 1.99).
“To our knowledge, this is the first investigation to systematically evaluate this association in a U.S. population of patients with HS,” the research team concluded.
The study was supported by a grant from AbbVie. Ms. Tannenbaum and Mr. Strunk reported no disclosures. Dr. Garg reported financial relationships with AbbVie and several other pharmaceutical companies.
SOURCE: Tannenbaum R et al. JAMA Dermatol. 2019 Jan 30. doi: 10.1001/jamadermatol.2018.5230.
FROM JAMA DERMATOLOGY
Key clinical point: Hidradenitis suppurativa appears to increase the risk of cutaneous T-cell lymphoma, Hodgkin, and non-Hodgkin lymphomas.
Major finding: Lymphomas are up to four times more common among patients with hidradenitis suppurativa than those without the chronic inflammatory disorder.
Study details: The database review comprised more than 55 million patients in 27 linked health care systems.
Disclosures: This study was supported by a grant from AbbVie. Ms. Tannenbaum and Mr. Strunk reported no disclosures. Dr. Garg reported financial relationships with AbbVie and several other pharmaceutical companies.
Source: Tannenbaum R et al. JAMA Dermatol. 2019 Jan 30. doi: 10.1001/jamadermatol.2018.5230.
What is your diagnosis?
It most commonly affects young girls. The pathogenesis of LAHS is thought to involve a sporadic, autosomal dominant mutation that leads to a defect between the hair cuticle and the inner root sheath.1 This defect results in the hair being poorly anchored to the scalp, and therefore easily and painlessly plucked or lost during normal hair care.
The classic presentation of LAHS is that of hair thinning and hair that may be unruly and/or lackluster; the hair rarely, if ever, requires cutting.2 The key feature is the ability to easily and painlessly pluck hairs from the patient’s scalp. The affected area is limited to the scalp, and loss of eyebrows, eyelashes, and body hair should not be seen.
Diagnosis and consideration of the differential
The diagnosis of LAHS can in some cases be made on history and physical exam alone. Patients with LAHS typically will show hair thinning with or without dullness or unruliness. They lack evidence of scalp inflammation, such as erythema, scale, pruritus, and pain. Areas of hair thinning or aberration are typically not well demarcated, and there are typically not areas of complete hair loss. There is no scarring or atrophy of the scalp itself.
Diagnostic tests include the “hair pull test,” as well as trichogram testing. In the “hair pull test” a provider grasps a set of hair at the proximal shaft near the scalp. The traction applied should result in the painless and easy extraction of more than 10% of grasped hairs in a patient with LAHS. Removal of less than 10% of hair is a normal finding, as patients without LAHS typically have about 10% of their scalp hair in the telogen phase at any given time, which would result in removal during the hair pull test.3 In trichography, plucked hairs are examined under magnification, with or without the use of selective dyes. Cinnamaldehyde is a dye that stains citrulline, which is abundant in the inner root sheath, and can be a tool in identifying its presence and/or aberrations.4 A trichogram of the pulled hairs in a patient with LAHS may classically show ruffled appearance of the cuticle, misshapen anagen hair bulbs, and absence of the inner root sheath.5 Examination under magnification also allows providers to better identify telogen versus anagen hairs, which aids in the diagnosis. By carefully considering the patient history, physical exam, and results of additional hair tests, providers can make the diagnosis of LAHS and avoid unnecessary blood work and invasive procedures like scalp biopsies.
The differential diagnosis of hair loss frequently includes alopecia areata. However, in alopecia areata, patients typically have sharply demarcated areas of hair loss, which may involve the eyebrows, eyelids, and body hairs. In alopecia areata, providers may be able to identify the “exclamation point sign” in which the hair shaft thins proximally, leading to the appearance of more pigmented, thicker hairs floating above the scalp.
Telogen effluvium is a condition in which a medical illness or stress, such as systemic illness, surgery, severe emotional distress, childbirth, dietary changes, or another traumatic event, causes a disruption in the natural cycle of hair growth such that the percentage of hairs in the telogen phase increases from about 10% to up to 70%.6 Unlike in LAHS, in which shed hairs are in the anagen phase, the hair that is shed in telogen effluvium is in the telogen phase and will have a different appearance when magnified.
Anagen effluvium, loss of hairs in their growing phase, is typically associated with chemotherapy. The hairs become broken and fractured at the shaft leading to breakage at different points throughout the scalp. Affected areas can include the eyebrows, eyelashes, and body hair. In the absence of a history of administration of a chemotherapy agent (or other drug known to trigger hair loss), the diagnosis of anagen effluvium should not be made.
Patients with trichotillosis (also known as trichotillomania) present with areas of hair loss caused by intentional or subconscious hair pulling. It is considered a psychological condition that can be associated with obsessive compulsive disorder, although the presence of a secondary psychological diagnosis is not required. Providers may see irregular geometric shapes of hair loss, and on close inspection see broken hair shafts of different lengths. Patients most often pull hair from their scalps (over 70% of patients), but also can pull eyelashes, eyebrow hairs, and pubic hairs.7
Treatment
LAHS is self-limited and does not necessitate treatment. However, if patients or parents feel there is significant disease burden, perhaps with poor effects on quality of life or with psychosocial impairment, treatment with minoxidil 5% solution has been studied with some success reported in the literature.1,8,9
Ms. Natsis is a medical student at the University of California, San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital-San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. Ms. Natsis and Dr. Eichenfield had no relevant financial disclosures. Email them at [email protected].
References
1. Arch Dermatol. 2002;138(4):501-6.
2. Int J Trichology. 2010;2(2):96-100.
3. Pediatric Dermatol. 2016:33(50):507-10.
4. Dermatol Clin. 1986;14:745-51.
5. Arch Dermatol. 2009;145(10):1123-8.
6. J Clin Diagn Res. 2015;9(9):WE01-3.
7. Am J Psychiatry. 2016;173(9):868-74.
8. Australas J Dermatol. 2018;59:e286-e287.
9. Pediatr Dermatol. 2014;31:389-90.
It most commonly affects young girls. The pathogenesis of LAHS is thought to involve a sporadic, autosomal dominant mutation that leads to a defect between the hair cuticle and the inner root sheath.1 This defect results in the hair being poorly anchored to the scalp, and therefore easily and painlessly plucked or lost during normal hair care.
The classic presentation of LAHS is that of hair thinning and hair that may be unruly and/or lackluster; the hair rarely, if ever, requires cutting.2 The key feature is the ability to easily and painlessly pluck hairs from the patient’s scalp. The affected area is limited to the scalp, and loss of eyebrows, eyelashes, and body hair should not be seen.
Diagnosis and consideration of the differential
The diagnosis of LAHS can in some cases be made on history and physical exam alone. Patients with LAHS typically will show hair thinning with or without dullness or unruliness. They lack evidence of scalp inflammation, such as erythema, scale, pruritus, and pain. Areas of hair thinning or aberration are typically not well demarcated, and there are typically not areas of complete hair loss. There is no scarring or atrophy of the scalp itself.
Diagnostic tests include the “hair pull test,” as well as trichogram testing. In the “hair pull test” a provider grasps a set of hair at the proximal shaft near the scalp. The traction applied should result in the painless and easy extraction of more than 10% of grasped hairs in a patient with LAHS. Removal of less than 10% of hair is a normal finding, as patients without LAHS typically have about 10% of their scalp hair in the telogen phase at any given time, which would result in removal during the hair pull test.3 In trichography, plucked hairs are examined under magnification, with or without the use of selective dyes. Cinnamaldehyde is a dye that stains citrulline, which is abundant in the inner root sheath, and can be a tool in identifying its presence and/or aberrations.4 A trichogram of the pulled hairs in a patient with LAHS may classically show ruffled appearance of the cuticle, misshapen anagen hair bulbs, and absence of the inner root sheath.5 Examination under magnification also allows providers to better identify telogen versus anagen hairs, which aids in the diagnosis. By carefully considering the patient history, physical exam, and results of additional hair tests, providers can make the diagnosis of LAHS and avoid unnecessary blood work and invasive procedures like scalp biopsies.
The differential diagnosis of hair loss frequently includes alopecia areata. However, in alopecia areata, patients typically have sharply demarcated areas of hair loss, which may involve the eyebrows, eyelids, and body hairs. In alopecia areata, providers may be able to identify the “exclamation point sign” in which the hair shaft thins proximally, leading to the appearance of more pigmented, thicker hairs floating above the scalp.
Telogen effluvium is a condition in which a medical illness or stress, such as systemic illness, surgery, severe emotional distress, childbirth, dietary changes, or another traumatic event, causes a disruption in the natural cycle of hair growth such that the percentage of hairs in the telogen phase increases from about 10% to up to 70%.6 Unlike in LAHS, in which shed hairs are in the anagen phase, the hair that is shed in telogen effluvium is in the telogen phase and will have a different appearance when magnified.
Anagen effluvium, loss of hairs in their growing phase, is typically associated with chemotherapy. The hairs become broken and fractured at the shaft leading to breakage at different points throughout the scalp. Affected areas can include the eyebrows, eyelashes, and body hair. In the absence of a history of administration of a chemotherapy agent (or other drug known to trigger hair loss), the diagnosis of anagen effluvium should not be made.
Patients with trichotillosis (also known as trichotillomania) present with areas of hair loss caused by intentional or subconscious hair pulling. It is considered a psychological condition that can be associated with obsessive compulsive disorder, although the presence of a secondary psychological diagnosis is not required. Providers may see irregular geometric shapes of hair loss, and on close inspection see broken hair shafts of different lengths. Patients most often pull hair from their scalps (over 70% of patients), but also can pull eyelashes, eyebrow hairs, and pubic hairs.7
Treatment
LAHS is self-limited and does not necessitate treatment. However, if patients or parents feel there is significant disease burden, perhaps with poor effects on quality of life or with psychosocial impairment, treatment with minoxidil 5% solution has been studied with some success reported in the literature.1,8,9
Ms. Natsis is a medical student at the University of California, San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital-San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. Ms. Natsis and Dr. Eichenfield had no relevant financial disclosures. Email them at [email protected].
References
1. Arch Dermatol. 2002;138(4):501-6.
2. Int J Trichology. 2010;2(2):96-100.
3. Pediatric Dermatol. 2016:33(50):507-10.
4. Dermatol Clin. 1986;14:745-51.
5. Arch Dermatol. 2009;145(10):1123-8.
6. J Clin Diagn Res. 2015;9(9):WE01-3.
7. Am J Psychiatry. 2016;173(9):868-74.
8. Australas J Dermatol. 2018;59:e286-e287.
9. Pediatr Dermatol. 2014;31:389-90.
It most commonly affects young girls. The pathogenesis of LAHS is thought to involve a sporadic, autosomal dominant mutation that leads to a defect between the hair cuticle and the inner root sheath.1 This defect results in the hair being poorly anchored to the scalp, and therefore easily and painlessly plucked or lost during normal hair care.
The classic presentation of LAHS is that of hair thinning and hair that may be unruly and/or lackluster; the hair rarely, if ever, requires cutting.2 The key feature is the ability to easily and painlessly pluck hairs from the patient’s scalp. The affected area is limited to the scalp, and loss of eyebrows, eyelashes, and body hair should not be seen.
Diagnosis and consideration of the differential
The diagnosis of LAHS can in some cases be made on history and physical exam alone. Patients with LAHS typically will show hair thinning with or without dullness or unruliness. They lack evidence of scalp inflammation, such as erythema, scale, pruritus, and pain. Areas of hair thinning or aberration are typically not well demarcated, and there are typically not areas of complete hair loss. There is no scarring or atrophy of the scalp itself.
Diagnostic tests include the “hair pull test,” as well as trichogram testing. In the “hair pull test” a provider grasps a set of hair at the proximal shaft near the scalp. The traction applied should result in the painless and easy extraction of more than 10% of grasped hairs in a patient with LAHS. Removal of less than 10% of hair is a normal finding, as patients without LAHS typically have about 10% of their scalp hair in the telogen phase at any given time, which would result in removal during the hair pull test.3 In trichography, plucked hairs are examined under magnification, with or without the use of selective dyes. Cinnamaldehyde is a dye that stains citrulline, which is abundant in the inner root sheath, and can be a tool in identifying its presence and/or aberrations.4 A trichogram of the pulled hairs in a patient with LAHS may classically show ruffled appearance of the cuticle, misshapen anagen hair bulbs, and absence of the inner root sheath.5 Examination under magnification also allows providers to better identify telogen versus anagen hairs, which aids in the diagnosis. By carefully considering the patient history, physical exam, and results of additional hair tests, providers can make the diagnosis of LAHS and avoid unnecessary blood work and invasive procedures like scalp biopsies.
The differential diagnosis of hair loss frequently includes alopecia areata. However, in alopecia areata, patients typically have sharply demarcated areas of hair loss, which may involve the eyebrows, eyelids, and body hairs. In alopecia areata, providers may be able to identify the “exclamation point sign” in which the hair shaft thins proximally, leading to the appearance of more pigmented, thicker hairs floating above the scalp.
Telogen effluvium is a condition in which a medical illness or stress, such as systemic illness, surgery, severe emotional distress, childbirth, dietary changes, or another traumatic event, causes a disruption in the natural cycle of hair growth such that the percentage of hairs in the telogen phase increases from about 10% to up to 70%.6 Unlike in LAHS, in which shed hairs are in the anagen phase, the hair that is shed in telogen effluvium is in the telogen phase and will have a different appearance when magnified.
Anagen effluvium, loss of hairs in their growing phase, is typically associated with chemotherapy. The hairs become broken and fractured at the shaft leading to breakage at different points throughout the scalp. Affected areas can include the eyebrows, eyelashes, and body hair. In the absence of a history of administration of a chemotherapy agent (or other drug known to trigger hair loss), the diagnosis of anagen effluvium should not be made.
Patients with trichotillosis (also known as trichotillomania) present with areas of hair loss caused by intentional or subconscious hair pulling. It is considered a psychological condition that can be associated with obsessive compulsive disorder, although the presence of a secondary psychological diagnosis is not required. Providers may see irregular geometric shapes of hair loss, and on close inspection see broken hair shafts of different lengths. Patients most often pull hair from their scalps (over 70% of patients), but also can pull eyelashes, eyebrow hairs, and pubic hairs.7
Treatment
LAHS is self-limited and does not necessitate treatment. However, if patients or parents feel there is significant disease burden, perhaps with poor effects on quality of life or with psychosocial impairment, treatment with minoxidil 5% solution has been studied with some success reported in the literature.1,8,9
Ms. Natsis is a medical student at the University of California, San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital-San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. Ms. Natsis and Dr. Eichenfield had no relevant financial disclosures. Email them at [email protected].
References
1. Arch Dermatol. 2002;138(4):501-6.
2. Int J Trichology. 2010;2(2):96-100.
3. Pediatric Dermatol. 2016:33(50):507-10.
4. Dermatol Clin. 1986;14:745-51.
5. Arch Dermatol. 2009;145(10):1123-8.
6. J Clin Diagn Res. 2015;9(9):WE01-3.
7. Am J Psychiatry. 2016;173(9):868-74.
8. Australas J Dermatol. 2018;59:e286-e287.
9. Pediatr Dermatol. 2014;31:389-90.
A 5-year-old female is brought to clinic for hair loss. The mother reports that when styling her daughter's hair, she has noticed areas of hair thinning, especially at the temples and at the occiput. The mother denies scale, pruritus, and erythema. The patient reports that her scalp does not hurt. She has never had a haircut because her hair hasn't grown long enough to cut. There is no history of specific bald spots. The patient has no personal history of psoriasis, seborrheic dermatitis, or autoimmune disease. No picking has been noted, and there is no history of compulsive behaviors or anxiety. The patient's mother has a history of Graves disease. The mother reports that the patient's older sister may have had hair thinning when she was younger as well, but no longer has thin hair.
The patient was previously seen by another provider who prescribed hydrocortisone 2.5% ointment, which the mother has been applying nightly without improvement.
The child is otherwise medically well and thriving, with no recent change in activity level and with growth parameters consistently around the 75th percentile for height and weight. On physical exam, the patient has blondish, fine hair with areas of poorly demarcated hair thinning at the left temple and at the occiput. The hair remaining at the occiput is normal in texture. There are no areas of complete hair loss. There is no scale, erythema, or abnormal pigmentation, and no cervical or occipital adenopathy. The patient has intact eyebrows and eyelashes.
Adolescence does not rule out bullous pemphigoid
Although there are only 14 cases in the literature, it should still be kept in mind, wrote investigators led by Aikaterini Patsatsi, MD, PhD, of Aristotle University, Thessaloniki, Greece, and senior author Victoria Werth, MD, of the University of Pennsylvania, Philadelphia.
The good news is that the course of adolescent bullous pemphigoid “seems favorable, with long remission after disease control,” the investigators reported in Pediatric Dermatology.
Bullous pemphigoid (BP) is the most common autoimmune blistering disease in the elderly, but is rare in children, with the majority of pediatric cases occurring in early childhood. Even so, BP is still possible in adolescents, and should be worked up with “salt‐split skin [testing] in all cases, and the detection of circulating anti-BP180 and anti‐BP230 autoantibodies by ELISA [enzyme-linked immunosorbent assay] tests, not routinely done for this diagnosis,” the investigators wrote.
BP hasn’t been well characterized in teenagers, so Dr. Patsatsi and her associates searched Medline for “bullous pemphigoid in childhood and adolescence,” “childhood bullous pemphigoid,” “juvenile bullous pemphigoid,” and “autoimmune blistering and autoimmune bullous diseases in childhood.”
It turned out that “all authors agree that the management plan should be the least aggressive possible” with “the addition of immunomodulating agents such as dapsone, azathioprine, mycophenolate mofetil, or doxycycline/niacinamide,” although systemic steroids were used in 13 of the 14 cases, the investigators wrote.
They found nine cases in children aged 10‐13 years (six in girls, two in boys, and one case with no sex identified), with the first case reported in 1970. Five had mucosal involvement. One case was diagnosed as localized BP of the perineum. The children were treated with systemic prednisone (eight of nine), in combination with dapsone (two of nine), azathioprine (two of nine), and erythromycin/nicotinamide (one of nine). Three relapsed; there was no report of what was done for them or how they fared.
“The clinical features of BP in this age range include a pruritic generalized bullous eruption, similar to ... adult BP, with frequent involvement of the oral mucosa,” Dr. Patsatsi and her associates wrote.
The team also found five cases in children aged 14‐17 years (three girls, two boys), with the first reported in 1994. None had mucosal involvement. Treatment included systemic prednisone (five of five), in combination with dapsone (three of five), azathioprine (two of five), doxycycline/nicotinamide (one of five), and mycophenolate mofetil (one of five). Two cases relapsed; subsequent treatment and outcomes weren’t reported.
The clinical features again were similar to those seen in adults, “with disseminated tense blisters and erosions,” the investigators noted.
Only one case was reported in adolescents aged 18-21 years, though it was excluded from the review because it overlapped with pemphigus vulgaris.
No funding and no relevant financial disclosures were reported for the work.
SOURCE: Patsatsi A et al. Pediatr Dermatol. 2018 Dec 19. doi: 10.1111/pde.13717.
Although there are only 14 cases in the literature, it should still be kept in mind, wrote investigators led by Aikaterini Patsatsi, MD, PhD, of Aristotle University, Thessaloniki, Greece, and senior author Victoria Werth, MD, of the University of Pennsylvania, Philadelphia.
The good news is that the course of adolescent bullous pemphigoid “seems favorable, with long remission after disease control,” the investigators reported in Pediatric Dermatology.
Bullous pemphigoid (BP) is the most common autoimmune blistering disease in the elderly, but is rare in children, with the majority of pediatric cases occurring in early childhood. Even so, BP is still possible in adolescents, and should be worked up with “salt‐split skin [testing] in all cases, and the detection of circulating anti-BP180 and anti‐BP230 autoantibodies by ELISA [enzyme-linked immunosorbent assay] tests, not routinely done for this diagnosis,” the investigators wrote.
BP hasn’t been well characterized in teenagers, so Dr. Patsatsi and her associates searched Medline for “bullous pemphigoid in childhood and adolescence,” “childhood bullous pemphigoid,” “juvenile bullous pemphigoid,” and “autoimmune blistering and autoimmune bullous diseases in childhood.”
It turned out that “all authors agree that the management plan should be the least aggressive possible” with “the addition of immunomodulating agents such as dapsone, azathioprine, mycophenolate mofetil, or doxycycline/niacinamide,” although systemic steroids were used in 13 of the 14 cases, the investigators wrote.
They found nine cases in children aged 10‐13 years (six in girls, two in boys, and one case with no sex identified), with the first case reported in 1970. Five had mucosal involvement. One case was diagnosed as localized BP of the perineum. The children were treated with systemic prednisone (eight of nine), in combination with dapsone (two of nine), azathioprine (two of nine), and erythromycin/nicotinamide (one of nine). Three relapsed; there was no report of what was done for them or how they fared.
“The clinical features of BP in this age range include a pruritic generalized bullous eruption, similar to ... adult BP, with frequent involvement of the oral mucosa,” Dr. Patsatsi and her associates wrote.
The team also found five cases in children aged 14‐17 years (three girls, two boys), with the first reported in 1994. None had mucosal involvement. Treatment included systemic prednisone (five of five), in combination with dapsone (three of five), azathioprine (two of five), doxycycline/nicotinamide (one of five), and mycophenolate mofetil (one of five). Two cases relapsed; subsequent treatment and outcomes weren’t reported.
The clinical features again were similar to those seen in adults, “with disseminated tense blisters and erosions,” the investigators noted.
Only one case was reported in adolescents aged 18-21 years, though it was excluded from the review because it overlapped with pemphigus vulgaris.
No funding and no relevant financial disclosures were reported for the work.
SOURCE: Patsatsi A et al. Pediatr Dermatol. 2018 Dec 19. doi: 10.1111/pde.13717.
Although there are only 14 cases in the literature, it should still be kept in mind, wrote investigators led by Aikaterini Patsatsi, MD, PhD, of Aristotle University, Thessaloniki, Greece, and senior author Victoria Werth, MD, of the University of Pennsylvania, Philadelphia.
The good news is that the course of adolescent bullous pemphigoid “seems favorable, with long remission after disease control,” the investigators reported in Pediatric Dermatology.
Bullous pemphigoid (BP) is the most common autoimmune blistering disease in the elderly, but is rare in children, with the majority of pediatric cases occurring in early childhood. Even so, BP is still possible in adolescents, and should be worked up with “salt‐split skin [testing] in all cases, and the detection of circulating anti-BP180 and anti‐BP230 autoantibodies by ELISA [enzyme-linked immunosorbent assay] tests, not routinely done for this diagnosis,” the investigators wrote.
BP hasn’t been well characterized in teenagers, so Dr. Patsatsi and her associates searched Medline for “bullous pemphigoid in childhood and adolescence,” “childhood bullous pemphigoid,” “juvenile bullous pemphigoid,” and “autoimmune blistering and autoimmune bullous diseases in childhood.”
It turned out that “all authors agree that the management plan should be the least aggressive possible” with “the addition of immunomodulating agents such as dapsone, azathioprine, mycophenolate mofetil, or doxycycline/niacinamide,” although systemic steroids were used in 13 of the 14 cases, the investigators wrote.
They found nine cases in children aged 10‐13 years (six in girls, two in boys, and one case with no sex identified), with the first case reported in 1970. Five had mucosal involvement. One case was diagnosed as localized BP of the perineum. The children were treated with systemic prednisone (eight of nine), in combination with dapsone (two of nine), azathioprine (two of nine), and erythromycin/nicotinamide (one of nine). Three relapsed; there was no report of what was done for them or how they fared.
“The clinical features of BP in this age range include a pruritic generalized bullous eruption, similar to ... adult BP, with frequent involvement of the oral mucosa,” Dr. Patsatsi and her associates wrote.
The team also found five cases in children aged 14‐17 years (three girls, two boys), with the first reported in 1994. None had mucosal involvement. Treatment included systemic prednisone (five of five), in combination with dapsone (three of five), azathioprine (two of five), doxycycline/nicotinamide (one of five), and mycophenolate mofetil (one of five). Two cases relapsed; subsequent treatment and outcomes weren’t reported.
The clinical features again were similar to those seen in adults, “with disseminated tense blisters and erosions,” the investigators noted.
Only one case was reported in adolescents aged 18-21 years, though it was excluded from the review because it overlapped with pemphigus vulgaris.
No funding and no relevant financial disclosures were reported for the work.
SOURCE: Patsatsi A et al. Pediatr Dermatol. 2018 Dec 19. doi: 10.1111/pde.13717.
FROM PEDIATRIC DERMATOLOGY
Key clinical point: The course of adolescent bullous pemphigoid appears favorable, with long remission after the disease is controlled.
Major finding: The investigators found nine cases in children aged 10‐13 years, and five cases in children aged 14‐17 years.
Study details: A search in Medline detected 14 adolescents with a diagnosis of bullous pemphigoid.
Disclosures: No funding and no relevant financial disclosures were reported for the work.
Source: Patsatsi A et al. Pediatr Dermatol. 2018 Dec 19. doi: 10.1111/pde.13717.
Different disease features found with family history of psoriasis versus PsA
the results of a retrospective cohort study suggest.
A family history of psoriasis was associated with younger onset of psoriatic disease and the presence of enthesitis, while by contrast, a family history of psoriatic arthritis (PsA) was associated with lower risk of plaque psoriasis and higher risk of deformities, according to Dilek Solmaz, MD, of the University of Ottawa and her coauthors, who reported their findings in Arthritis Care & Research.
“The link between family history of psoriasis/psoriatic arthritis and pustular/plaque phenotypes may point to a different genetic background and pathogenic mechanisms in these subsets,” the investigators wrote.
Most, if not all, previous studies evaluating family history have grouped psoriasis and PsA together, according to Dr. Solmaz and her colleagues, rather than looking at the individual effects of psoriasis or PsA family history that may lead to unique disease phenotypes, as was done in the present study.
The investigators based their retrospective analysis on patients recruited in a longitudinal, multicenter database in Turkey and Canada. The mean age of patients in the study was 48 years; nearly 65% were female.
Out of 1,393 patients in the database, 444 had a family history of psoriasis or PsA. That included 335 patients with a psoriasis-only family history and 74 with a family history of PsA; another 35 patients weren’t sure about having a family history of PsA or psoriasis and were left out of the analysis.
Plaque psoriasis was more common in individuals with a family history of only psoriasis, while pustular psoriasis was more common in those with a PsA family history, the investigators reported.
In multivariate analyses, having a family member with psoriasis was a risk factor for younger age of psoriasis onset (odds ratio, 0.976; 95% confidence interval, 0.964-0.989; P less than .001) as well as a higher risk for enthesitis (OR, 1.931; 95% CI, 1.276-2.922; P = .002) when compared against patients without a family history of psoriasis.
Patients with a family history of PsA were more likely to have deformities (OR, 2.557; 95% CI, 1.250-5.234; P less than .010) and lower risk of plaque-type psoriasis (OR, 0.417; 95% CI, 0.213-0.816; P less than .011) than patients without a family history of PsA.
Disease onset was earlier among patients with a family history of psoriasis at a mean of 28.1 years versus 31.9 years for those with a family history of PsA (P less than .001).
Dr. Solmaz and her colleagues reported no conflicts of interest related to the research, which was supported in part by the Turkish Society for Rheumatology, the Scientific and Technological Research Council of Turkey, and Union Chimique Belge.
SOURCE: Solmaz D et al. Arthritis Care Res (Hoboken). 2019 Jan 25. doi: 10.1002/acr.23836.
the results of a retrospective cohort study suggest.
A family history of psoriasis was associated with younger onset of psoriatic disease and the presence of enthesitis, while by contrast, a family history of psoriatic arthritis (PsA) was associated with lower risk of plaque psoriasis and higher risk of deformities, according to Dilek Solmaz, MD, of the University of Ottawa and her coauthors, who reported their findings in Arthritis Care & Research.
“The link between family history of psoriasis/psoriatic arthritis and pustular/plaque phenotypes may point to a different genetic background and pathogenic mechanisms in these subsets,” the investigators wrote.
Most, if not all, previous studies evaluating family history have grouped psoriasis and PsA together, according to Dr. Solmaz and her colleagues, rather than looking at the individual effects of psoriasis or PsA family history that may lead to unique disease phenotypes, as was done in the present study.
The investigators based their retrospective analysis on patients recruited in a longitudinal, multicenter database in Turkey and Canada. The mean age of patients in the study was 48 years; nearly 65% were female.
Out of 1,393 patients in the database, 444 had a family history of psoriasis or PsA. That included 335 patients with a psoriasis-only family history and 74 with a family history of PsA; another 35 patients weren’t sure about having a family history of PsA or psoriasis and were left out of the analysis.
Plaque psoriasis was more common in individuals with a family history of only psoriasis, while pustular psoriasis was more common in those with a PsA family history, the investigators reported.
In multivariate analyses, having a family member with psoriasis was a risk factor for younger age of psoriasis onset (odds ratio, 0.976; 95% confidence interval, 0.964-0.989; P less than .001) as well as a higher risk for enthesitis (OR, 1.931; 95% CI, 1.276-2.922; P = .002) when compared against patients without a family history of psoriasis.
Patients with a family history of PsA were more likely to have deformities (OR, 2.557; 95% CI, 1.250-5.234; P less than .010) and lower risk of plaque-type psoriasis (OR, 0.417; 95% CI, 0.213-0.816; P less than .011) than patients without a family history of PsA.
Disease onset was earlier among patients with a family history of psoriasis at a mean of 28.1 years versus 31.9 years for those with a family history of PsA (P less than .001).
Dr. Solmaz and her colleagues reported no conflicts of interest related to the research, which was supported in part by the Turkish Society for Rheumatology, the Scientific and Technological Research Council of Turkey, and Union Chimique Belge.
SOURCE: Solmaz D et al. Arthritis Care Res (Hoboken). 2019 Jan 25. doi: 10.1002/acr.23836.
the results of a retrospective cohort study suggest.
A family history of psoriasis was associated with younger onset of psoriatic disease and the presence of enthesitis, while by contrast, a family history of psoriatic arthritis (PsA) was associated with lower risk of plaque psoriasis and higher risk of deformities, according to Dilek Solmaz, MD, of the University of Ottawa and her coauthors, who reported their findings in Arthritis Care & Research.
“The link between family history of psoriasis/psoriatic arthritis and pustular/plaque phenotypes may point to a different genetic background and pathogenic mechanisms in these subsets,” the investigators wrote.
Most, if not all, previous studies evaluating family history have grouped psoriasis and PsA together, according to Dr. Solmaz and her colleagues, rather than looking at the individual effects of psoriasis or PsA family history that may lead to unique disease phenotypes, as was done in the present study.
The investigators based their retrospective analysis on patients recruited in a longitudinal, multicenter database in Turkey and Canada. The mean age of patients in the study was 48 years; nearly 65% were female.
Out of 1,393 patients in the database, 444 had a family history of psoriasis or PsA. That included 335 patients with a psoriasis-only family history and 74 with a family history of PsA; another 35 patients weren’t sure about having a family history of PsA or psoriasis and were left out of the analysis.
Plaque psoriasis was more common in individuals with a family history of only psoriasis, while pustular psoriasis was more common in those with a PsA family history, the investigators reported.
In multivariate analyses, having a family member with psoriasis was a risk factor for younger age of psoriasis onset (odds ratio, 0.976; 95% confidence interval, 0.964-0.989; P less than .001) as well as a higher risk for enthesitis (OR, 1.931; 95% CI, 1.276-2.922; P = .002) when compared against patients without a family history of psoriasis.
Patients with a family history of PsA were more likely to have deformities (OR, 2.557; 95% CI, 1.250-5.234; P less than .010) and lower risk of plaque-type psoriasis (OR, 0.417; 95% CI, 0.213-0.816; P less than .011) than patients without a family history of PsA.
Disease onset was earlier among patients with a family history of psoriasis at a mean of 28.1 years versus 31.9 years for those with a family history of PsA (P less than .001).
Dr. Solmaz and her colleagues reported no conflicts of interest related to the research, which was supported in part by the Turkish Society for Rheumatology, the Scientific and Technological Research Council of Turkey, and Union Chimique Belge.
SOURCE: Solmaz D et al. Arthritis Care Res (Hoboken). 2019 Jan 25. doi: 10.1002/acr.23836.
FROM ARTHRITIS CARE & RESEARCH
Key clinical point: Family histories of psoriasis and psoriatic arthritis were linked to different skin phenotypes, disease severity, and musculoskeletal features.
Major finding: Compared with no family history, psoriasis family history was a risk factor for enthesitis (odds ratio, 1.931) and younger age of onset (OR, 0.976) while psoriatic arthritis family history was linked to higher risk of deformities (OR, 2.557) and lower risk of plaque-type psoriasis (OR, 0.417).
Study details: A retrospective analysis including 1,393 Turkish or Canadian patients enrolled in a psoriatic arthritis database.
Disclosures: The study authors reported no conflicts of interest related to the research, which was supported in part by the Turkish Society for Rheumatology, the Scientific and Technological Research Council of Turkey, and Union Chimique Belge.
Source: Solmaz D et al. Arthritis Care Res (Hoboken). 2019 Jan 25. doi: 10.1002/acr.23836.
Black lesion on arm
Due to the dark and rapidly growing nodule, the FP immediately worried about melanoma.
He thought that he should biopsy the entire lesion with an elliptical excision, so he scheduled the patient for a biopsy during some protected surgical time later that week. The patient did not show up for this appointment. Several calls were placed, and she returned for the biopsy the following week. The FP performed a narrow margin (2 mm) elliptical excision oriented to match the lymphatic drainage of the arm. He closed the excision with a 2-layer closure. (See the Watch & Learn video on elliptical excision.) The pathology report confirmed that it was a nodular melanoma that was 8 mm in depth. This was clearly an aggressive tumor, so the patient was referred to Surgical Oncology for sentinel lymph node biopsy. One node was positive for metastasis.
After a wide excision with 2 cm margins by Surgical Oncology, the patient underwent a course of chemotherapy and remained disease free 2 years later. She was carefully monitored for metastasis and new primary lesions by a multidisciplinary team that included family medicine, dermatology, and oncology.
While this FP handled the case in an excellent matter, he was fortunate to have the skills and time to be able to perform a full elliptical excision. It’s important to note that a 6 mm punch biopsy or a deep shave biopsy (saucerization) at the base of the thickest portion of this tumor would almost certainly have provided the same diagnosis of melanoma and at least showed that the tumor was thicker than 4 mm (an important cut-off for management). This could have been done on the day of original presentation and might have avoided the problem of the patient not showing up for the next appointment or a long delay to see a dermatologist.
FPs should be empowered to perform biopsies on the most worrisome of lesions as these biopsies can save lives. While incomplete sampling can result in false negative results and misdiagnosis, the protection against this is to not accept a benign pathology report in what appears to be an obvious malignancy. If this occurs, the next step is always complete excision. Having options and understanding potential sampling errors can help FPs diagnose patients more rapidly. This is essential when cancers are rapidly growing and delays of months for surgical appointments or referrals to specialists can worsen a prognosis.
Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Karnes J, Usatine R. Melanoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1112-1123.
To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/
You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com
Due to the dark and rapidly growing nodule, the FP immediately worried about melanoma.
He thought that he should biopsy the entire lesion with an elliptical excision, so he scheduled the patient for a biopsy during some protected surgical time later that week. The patient did not show up for this appointment. Several calls were placed, and she returned for the biopsy the following week. The FP performed a narrow margin (2 mm) elliptical excision oriented to match the lymphatic drainage of the arm. He closed the excision with a 2-layer closure. (See the Watch & Learn video on elliptical excision.) The pathology report confirmed that it was a nodular melanoma that was 8 mm in depth. This was clearly an aggressive tumor, so the patient was referred to Surgical Oncology for sentinel lymph node biopsy. One node was positive for metastasis.
After a wide excision with 2 cm margins by Surgical Oncology, the patient underwent a course of chemotherapy and remained disease free 2 years later. She was carefully monitored for metastasis and new primary lesions by a multidisciplinary team that included family medicine, dermatology, and oncology.
While this FP handled the case in an excellent matter, he was fortunate to have the skills and time to be able to perform a full elliptical excision. It’s important to note that a 6 mm punch biopsy or a deep shave biopsy (saucerization) at the base of the thickest portion of this tumor would almost certainly have provided the same diagnosis of melanoma and at least showed that the tumor was thicker than 4 mm (an important cut-off for management). This could have been done on the day of original presentation and might have avoided the problem of the patient not showing up for the next appointment or a long delay to see a dermatologist.
FPs should be empowered to perform biopsies on the most worrisome of lesions as these biopsies can save lives. While incomplete sampling can result in false negative results and misdiagnosis, the protection against this is to not accept a benign pathology report in what appears to be an obvious malignancy. If this occurs, the next step is always complete excision. Having options and understanding potential sampling errors can help FPs diagnose patients more rapidly. This is essential when cancers are rapidly growing and delays of months for surgical appointments or referrals to specialists can worsen a prognosis.
Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Karnes J, Usatine R. Melanoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1112-1123.
To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/
You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com
Due to the dark and rapidly growing nodule, the FP immediately worried about melanoma.
He thought that he should biopsy the entire lesion with an elliptical excision, so he scheduled the patient for a biopsy during some protected surgical time later that week. The patient did not show up for this appointment. Several calls were placed, and she returned for the biopsy the following week. The FP performed a narrow margin (2 mm) elliptical excision oriented to match the lymphatic drainage of the arm. He closed the excision with a 2-layer closure. (See the Watch & Learn video on elliptical excision.) The pathology report confirmed that it was a nodular melanoma that was 8 mm in depth. This was clearly an aggressive tumor, so the patient was referred to Surgical Oncology for sentinel lymph node biopsy. One node was positive for metastasis.
After a wide excision with 2 cm margins by Surgical Oncology, the patient underwent a course of chemotherapy and remained disease free 2 years later. She was carefully monitored for metastasis and new primary lesions by a multidisciplinary team that included family medicine, dermatology, and oncology.
While this FP handled the case in an excellent matter, he was fortunate to have the skills and time to be able to perform a full elliptical excision. It’s important to note that a 6 mm punch biopsy or a deep shave biopsy (saucerization) at the base of the thickest portion of this tumor would almost certainly have provided the same diagnosis of melanoma and at least showed that the tumor was thicker than 4 mm (an important cut-off for management). This could have been done on the day of original presentation and might have avoided the problem of the patient not showing up for the next appointment or a long delay to see a dermatologist.
FPs should be empowered to perform biopsies on the most worrisome of lesions as these biopsies can save lives. While incomplete sampling can result in false negative results and misdiagnosis, the protection against this is to not accept a benign pathology report in what appears to be an obvious malignancy. If this occurs, the next step is always complete excision. Having options and understanding potential sampling errors can help FPs diagnose patients more rapidly. This is essential when cancers are rapidly growing and delays of months for surgical appointments or referrals to specialists can worsen a prognosis.
Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Karnes J, Usatine R. Melanoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1112-1123.
To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/
You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com
Psoriatic arthritis eludes early diagnosis
Most patients with psoriatic arthritis first present with psoriasis only. Their skin disorder precedes any joint involvement, often by several years. That suggests targeting interventions to patients with psoriasis to prevent or slow their progression to psoriatic arthritis, as well as following psoriatic patients closely to diagnose psoriatic arthritis quickly when it first appears. It’s a simple and attractive management premise that’s been challenging to apply in practice.
It’s not that clinicians aren’t motivated to diagnose psoriatic arthritis (PsA) in patients early, hopefully as soon as it appears. The susceptibility of patients with psoriasis to develop PsA is well described, with an annual progression rate of about 3%, and adverse consequences result from even a 6-month delay in diagnosis.
“Some physicians still don’t ask psoriasis patients about joint pain, or their symptoms are misinterpreted as something else,” said Lihi Eder, MD, a rheumatologist at Women’s College Research Institute, Toronto, and the University of Toronto. “Although there is increased awareness about PsA, there are still delays in diagnosis,” she said in an interview.
“Often there is a massive delay in diagnosis, and we know from a number of studies that longer duration of symptoms before diagnosis is associated with poorer outcomes,” said Laura C. Coates, MBChB, PhD, a rheumatologist at the University of Oxford (England). The delay to PsA diagnosis is generally “longer than for equivalent rheumatoid arthritis patients. PsA patients take longer to ask a primary care physician for help, longer to get a referral to a rheumatologist, and longer to get a diagnosis” from a rheumatologist. “We need to educate patients with psoriasis about their risk so that they seek help, educate GPs about whom to refer, and educate rheumatologists about diagnosis,” Dr. Coates said.
“It is very important to diagnose PsA as early as possible. We know that a delay in diagnosis and treatment can lead to worse outcomes and joint damage,” said Soumya M. Reddy, MD, codirector of the Psoriasis and Psoriatic Arthritis Center at New York University Langone Health in New York. “The heterogeneity of clinical manifestations of PsA can make it difficult to diagnose, and in some cases this leads to delayed diagnosis.”
“We are increasingly interested in the concept of preventing PsA. Psoriasis is a unique disease state in which we have an at-risk population where 30% will develop an inflammatory and potentially damaging arthritis. This may become important as our skin treatments may also treat musculoskeletal components of the disease,” said Joseph F. Merola, MD, director of the Center for Skin and Related Musculoskeletal Diseases at Brigham and Women’s Hospital in Boston and double board certified in dermatology and rheumatology.
Focusing on patients with psoriasis
Treatment of psoriasis makes sense to address several quality-of-life issues, but controlling the severity of psoriatic skin manifestations gives patients no guarantees about their possible progression to PsA.
“So many people have mild psoriasis that, although they are less likely, proportionately, to get PsA, we still see many in the clinic,” said Dr. Coates. “Patients with severe skin involvement have a good reason to get treatment, which could help test whether a drug slows progression to arthritis. But it’s unethical to not treat severe psoriasis just to have a comparison group.” Aside from skin psoriasis, “we don’t have any other good markers,” Dr. Coates noted.
PsA can develop in patients who had psoriasis in the past but without currently active disease. “At the level of individual patients you can’t say someone is protected from developing PsA because their psoriasis is inactive,” Dr. Eder said. “No study has looked at whether treatment of psoriasis reduces the risk for progression to PsA. We don’t know whether any treatments that reduce inflammation in psoriasis also reduce progression to PsA.” Regardless, treating psoriasis is important because it improves quality of life and may have a beneficial, long-term effects on possible cardiovascular disease effects from psoriasis, Dr. Eder said.
Her research group is now studying the associations among different biological drugs taken by patients with psoriasis and their subsequent incidence of PsA with use of medical records from about 4 million Israeli residents. Other studies are also looking at this, but they are all observational and therefore are subject to unidentified confounders, she noted. A more definitive demonstration of PsA protection would need a randomized trial.
“The idea of preventing the transition from psoriasis to PsA is an exciting concept. But currently, there are no established treatments for preventing transition of psoriasis to PsA. It’s an area of active research, and the holy grail of psoriatic disease research. We do not yet know whether successful treatment of skin psoriasis delays the onset of arthritis,” Dr. Reddy said in an interview.
“The risk of developing PsA increases as the severity of skin psoriasis increases, measured by percentage of body surface area affected. However, there is only a weak correlation between the severity of skin disease and the severity of PsA,” said Joel M. Gelfand, MD, professor of dermatology at the University of Pennsylvania in Philadelphia.
Widening the PsA diagnostic net
What’s elusive is some other parameter to identify the 3% of psoriasis patients who will develop PsA during the next year – or at least a better way to find patients as soon as they have what is identifiably PsA.
The diagnostic definition for PsA that many experts now accept is actually a set of classification criteria, CASPAR (Classification Criteria for Psoriatic Arthritis) (Arthritis Rheum. 2006 Aug;54[8]:2665-73). But in actual practice, diagnosing PsA relies heavily on clinical skill, case recognition, and ruling out mimickers.
“The CASPAR criteria were developed as classification criteria to use in studies, but they are also quite helpful in diagnosing PsA. It is the agreed on definition of PsA at the moment,” said Alexis Ogdie, MD, director of the psoriatic arthritis clinic at the University of Pennsylvania.
“CASPAR fills the role at present for clinical trials, but the diagnosis remains clinical, based on history, physical findings, and supported by lab and radiology findings,” Dr. Merola said. “A clinical prediction tool and a proper biomarker would be of great value.”
“We certainly use CASPAR criteria in the clinic, but they do not include all PsA patients; sometimes we diagnose PsA in patients who don’t meet the CASPAR criteria,” Dr. Coates said.
“In practice, rheumatologists mostly use their clinical judgment: a patient with history and findings typical of PsA after ruling out other causes. But distinguishing inflammatory from noninflammatory arthritis – like osteoarthritis or fibromyalgia – can be quite difficult; that’s the main challenge,” Dr. Eder said. “Rheumatologists rely on their clinical skill and experience. PsA can be difficult to diagnose. There is no biomarker for it. PsA is complex [to diagnose], and that’s why it’s diagnosed later. A primary care physician might get a negative result on a rheumatoid factor test and think that rules out PsA, but it doesn’t.”
Dr. Eder and others suggest that ultrasound may be a useful tool for earlier diagnosis of PsA. Ultrasound is more sensitive than a physical examination and can detect inflammation in joints and entheses, she noted. Another effective method may be more systematic use of screening questionnaires, Dr. Coates said, or simply more systematic questioning of patients.
“Questionnaires are not a high priority for a primary care physician who may have only a few patients with psoriasis. Even some dermatologists may not use the questionnaires because they take time to administer and assess. But just asking a psoriasis patient whether they have joint symptoms is enough,” Dr. Eder said. All clinicians who encounter patients with psoriasis should ask about musculoskeletal symptoms and refer when appropriate to a rheumatologist, Dr. Reddy said.
The earliest indicators of PsA
Evidence supporting ultrasound’s value for early PsA diagnosis came in a report at the most recent annual meeting of the American College of Rheumatology in Chicago in October 2018. Researchers from the University of Rochester (New York) used ultrasound to examine 78 patients with psoriasis but without PsA or musculoskeletal symptoms and 25 healthy controls. They found ultrasound abnormalities in almost half of the patients with psoriasis, significantly more than in the controls (Thiele R et al. Arthritis Rheumatol. 2018;70[suppl 10]: Abstract 2904).
Another report at the ACR annual meeting last October looked at the incidence of physician visits for nonspecific musculoskeletal symptoms during each of the 5 years preceding diagnosis of PsA. A prior report from Dr. Eder and her associates had documented in an observational cohort of 410 patients with psoriasis that, prior to development of PsA, patients often had nonspecific musculoskeletal symptoms of joint pain, fatigue, and stiffness that constituted a “preclinical” phase (Arthritis Rheumatol. 2017 March;69[3]:622-9).
In October, Dr. Eder reported how the appearance of musculoskeletal symptoms played out in terms of physician visits. She and her associates analyzed data from an Ontario health insurance database that included about 430,000 Ontario patients seen by 466 primary care physicians, which included 462 patients with a new diagnosis of PsA and 2,310 matched controls. The results showed that, in every year during the 5 years preceding diagnosis of PsA, the patients who would wind up getting diagnosed had roughly twice the number of visits to a primary care physician each year for nonspecific musculoskeletal issues. A similar pattern of doubled visits occurred for people prior to their PsA diagnosis going to physicians who specialize in musculoskeletal conditions, and when the analysis focused on visits to rheumatologists, patients who went on to get diagnosed with PsA had a nearly sevenfold increased rate of these visits, compared with controls, for each of the 5 years preceding their PsA diagnosis (Eder L et al. Arthritis Rheumatol. 2018;70[suppl 10]: Abstract 967).
These results “highlight that in many patients PsA is not an acute disease that starts suddenly. In many patients, there is a period when the patient experiences musculoskeletal symptoms and sees a primary care physician or rheumatologist and may be diagnosed with something that is not PsA. That means that the delay in diagnosis [of PsA] may have happened because the patients were misdiagnosed. It reinforces the need for better diagnostic tools,” Dr. Eder said. “We have focused on getting these patients to see a rheumatologist earlier, but that may not be enough. These patients may not receive routine follow-up; we need to do more follow-up on patients like these.” Diagnosing PsA early means earlier treatment, a better chance of reaching remission, less chance of permanent joint damage, and better quality of life.
The challenges of making an early diagnosis were also documented in a study reported by Dr. Ogdie during the June 2018 annual congress of the European League Against Rheumatism. Dr. Ogdie reported on the survey responses of 203 patients who said they had been diagnosed with PsA whose index diagnosis was a median of 6 years before they completed the survey. A total of 195 of these patients, or 96%, said that they had received at least one misdiagnosis prior to their PsA diagnosis (Odgie A et al. Ann Rheum Dis. 2018;77[Suppl 2]:163. Abstract THU0292). The most common misdiagnoses were psychosomatic disease, reported by 27% of the patients; osteoarthritis in 22%; anxiety or depression in 18%; and an orthopedic problem in 18%. (Patients could report more than one type of misdiagnosis.)
The results “showed that patients often had substantial delays and misdiagnoses before they received a PsA diagnosis,” Dr. Ogdie and her associates concluded. Although the CASPAR classification criteria may be the agreed on PsA definition, recent findings suggest a pre-PsA stage exists with musculoskeletal and other abnormalities. “How may we diagnose ‘pre-PsA’? How might we capture this transition phase from psoriasis to PsA before the CASPAR criteria are fulfilled,” she wondered in an interview. “If we could stop PsA before it is clinically relevant, that could dramatically change the course of the disease. This is a big need in the field right now.”
Weight loss and other interventions
Aside from treating psoriasis and perhaps putting a patient with psoriasis in a PsA-prevention trial, one of the best ways to prevent PsA may be weight loss.
Results from “some studies suggest that being overweight increases the risk for developing PsA. Obesity also exacerbates skin psoriasis, makes treatment less effective, and further increases the risk of cardiometabolic diseases associated with psoriasis,” Dr. Gelfand said. “All patients with psoriatic disease should be educated about the importance of maintaining a healthy body weight.”
“Several studies suggest that obesity is a risk factor for developing PsA. Obesity likely plays a role in driving or contributing to inflammation in psoriatic disease,” said Dr. Reddy, who noted that other PsA risk factors include nail psoriasis and first-degree relatives with PsA. Dr. Ogdie also cited uveitis and prior joint trauma as other risk factors.
“Strong observational data link obesity and PsA incidence. I talk to psoriasis patients about weight control, and selected patients could even consider bariatric surgery,” Dr. Eder said. Losing at least 5% of body mass index can make a difference, she added.
At the 2018 annual meeting of the American College of Rheumatology, researchers from the University of Bath (England) reported results from a retrospective, observational study of more than 90,000 people with recent-onset psoriasis; they found that people with an obese BMI had twice the rate of progression to PsA when compared with people with a normal BMI. Overweight people had a nearly 80% higher rate of incident PsA (Green A et al. Arthritis Rheumatol. 2018;70[Suppl 10]: Abstract 2134).
Hints have also emerged that new approaches to treating psoriasis also could help to keep PsA precursors at bay. One recent example from researchers at the University of Leeds (England) was a phase 2 study of 73 patients with moderate to severe psoriasis but no PsA who underwent ultrasound screening of their entheses for signs of inflammatory changes. The 23 patients underwent 52 weeks of treatment with the drug ustekinumab (Stelara), an antagonist of interleukin-12 and -23 that is approved for U.S. marketing to treat both psoriasis and PsA. After 24 weeks on treatment, their mean inflammation scores had dropped by more than 40%, and the effect persisted through 52 weeks of treatment (Arthritis Rheum. 2018 Nov 22. doi: 10.1002/art.40778).
Despite this promise, the researchers “haven’t looked long enough or in enough people to see whether this actually stops patients from developing PsA,” Dr. Coates commented. It also remains unclear whether this or another ultrasound abnormality detectable in joints or entheses is a reliable predictor of PsA, she noted.
“We still have a lot to learn about how to classify patients as high risk” for PsA, Dr. Ogdie concluded.
Dr. Eder has received research and educational grants from AbbVie, Amgen, Celgene, Lilly, Novartis, and UCB. Dr. Coates has received honoraria, research funding, or both from more than a dozen companies. Dr. Reddy has been a consultant to AbbVie, Novartis, Pfizer, and UCB. Dr. Merola has been a consultant to AbbVie, Celgene, GlaxoSmithKline, Janssen, Lilly, Novartis, Samumed, Sanofi, and UCB and has received research grants from Aclaris, Biogen, Incyte, Novartis, Pfizer, and Sanofi. Dr. Gelfand has been a consultant, adviser, or both to more than a dozen companies. Dr. Ogdie has been a consultant to AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Corrona, Lilly, Novartis, Pfizer, and Takeda.
Most patients with psoriatic arthritis first present with psoriasis only. Their skin disorder precedes any joint involvement, often by several years. That suggests targeting interventions to patients with psoriasis to prevent or slow their progression to psoriatic arthritis, as well as following psoriatic patients closely to diagnose psoriatic arthritis quickly when it first appears. It’s a simple and attractive management premise that’s been challenging to apply in practice.
It’s not that clinicians aren’t motivated to diagnose psoriatic arthritis (PsA) in patients early, hopefully as soon as it appears. The susceptibility of patients with psoriasis to develop PsA is well described, with an annual progression rate of about 3%, and adverse consequences result from even a 6-month delay in diagnosis.
“Some physicians still don’t ask psoriasis patients about joint pain, or their symptoms are misinterpreted as something else,” said Lihi Eder, MD, a rheumatologist at Women’s College Research Institute, Toronto, and the University of Toronto. “Although there is increased awareness about PsA, there are still delays in diagnosis,” she said in an interview.
“Often there is a massive delay in diagnosis, and we know from a number of studies that longer duration of symptoms before diagnosis is associated with poorer outcomes,” said Laura C. Coates, MBChB, PhD, a rheumatologist at the University of Oxford (England). The delay to PsA diagnosis is generally “longer than for equivalent rheumatoid arthritis patients. PsA patients take longer to ask a primary care physician for help, longer to get a referral to a rheumatologist, and longer to get a diagnosis” from a rheumatologist. “We need to educate patients with psoriasis about their risk so that they seek help, educate GPs about whom to refer, and educate rheumatologists about diagnosis,” Dr. Coates said.
“It is very important to diagnose PsA as early as possible. We know that a delay in diagnosis and treatment can lead to worse outcomes and joint damage,” said Soumya M. Reddy, MD, codirector of the Psoriasis and Psoriatic Arthritis Center at New York University Langone Health in New York. “The heterogeneity of clinical manifestations of PsA can make it difficult to diagnose, and in some cases this leads to delayed diagnosis.”
“We are increasingly interested in the concept of preventing PsA. Psoriasis is a unique disease state in which we have an at-risk population where 30% will develop an inflammatory and potentially damaging arthritis. This may become important as our skin treatments may also treat musculoskeletal components of the disease,” said Joseph F. Merola, MD, director of the Center for Skin and Related Musculoskeletal Diseases at Brigham and Women’s Hospital in Boston and double board certified in dermatology and rheumatology.
Focusing on patients with psoriasis
Treatment of psoriasis makes sense to address several quality-of-life issues, but controlling the severity of psoriatic skin manifestations gives patients no guarantees about their possible progression to PsA.
“So many people have mild psoriasis that, although they are less likely, proportionately, to get PsA, we still see many in the clinic,” said Dr. Coates. “Patients with severe skin involvement have a good reason to get treatment, which could help test whether a drug slows progression to arthritis. But it’s unethical to not treat severe psoriasis just to have a comparison group.” Aside from skin psoriasis, “we don’t have any other good markers,” Dr. Coates noted.
PsA can develop in patients who had psoriasis in the past but without currently active disease. “At the level of individual patients you can’t say someone is protected from developing PsA because their psoriasis is inactive,” Dr. Eder said. “No study has looked at whether treatment of psoriasis reduces the risk for progression to PsA. We don’t know whether any treatments that reduce inflammation in psoriasis also reduce progression to PsA.” Regardless, treating psoriasis is important because it improves quality of life and may have a beneficial, long-term effects on possible cardiovascular disease effects from psoriasis, Dr. Eder said.
Her research group is now studying the associations among different biological drugs taken by patients with psoriasis and their subsequent incidence of PsA with use of medical records from about 4 million Israeli residents. Other studies are also looking at this, but they are all observational and therefore are subject to unidentified confounders, she noted. A more definitive demonstration of PsA protection would need a randomized trial.
“The idea of preventing the transition from psoriasis to PsA is an exciting concept. But currently, there are no established treatments for preventing transition of psoriasis to PsA. It’s an area of active research, and the holy grail of psoriatic disease research. We do not yet know whether successful treatment of skin psoriasis delays the onset of arthritis,” Dr. Reddy said in an interview.
“The risk of developing PsA increases as the severity of skin psoriasis increases, measured by percentage of body surface area affected. However, there is only a weak correlation between the severity of skin disease and the severity of PsA,” said Joel M. Gelfand, MD, professor of dermatology at the University of Pennsylvania in Philadelphia.
Widening the PsA diagnostic net
What’s elusive is some other parameter to identify the 3% of psoriasis patients who will develop PsA during the next year – or at least a better way to find patients as soon as they have what is identifiably PsA.
The diagnostic definition for PsA that many experts now accept is actually a set of classification criteria, CASPAR (Classification Criteria for Psoriatic Arthritis) (Arthritis Rheum. 2006 Aug;54[8]:2665-73). But in actual practice, diagnosing PsA relies heavily on clinical skill, case recognition, and ruling out mimickers.
“The CASPAR criteria were developed as classification criteria to use in studies, but they are also quite helpful in diagnosing PsA. It is the agreed on definition of PsA at the moment,” said Alexis Ogdie, MD, director of the psoriatic arthritis clinic at the University of Pennsylvania.
“CASPAR fills the role at present for clinical trials, but the diagnosis remains clinical, based on history, physical findings, and supported by lab and radiology findings,” Dr. Merola said. “A clinical prediction tool and a proper biomarker would be of great value.”
“We certainly use CASPAR criteria in the clinic, but they do not include all PsA patients; sometimes we diagnose PsA in patients who don’t meet the CASPAR criteria,” Dr. Coates said.
“In practice, rheumatologists mostly use their clinical judgment: a patient with history and findings typical of PsA after ruling out other causes. But distinguishing inflammatory from noninflammatory arthritis – like osteoarthritis or fibromyalgia – can be quite difficult; that’s the main challenge,” Dr. Eder said. “Rheumatologists rely on their clinical skill and experience. PsA can be difficult to diagnose. There is no biomarker for it. PsA is complex [to diagnose], and that’s why it’s diagnosed later. A primary care physician might get a negative result on a rheumatoid factor test and think that rules out PsA, but it doesn’t.”
Dr. Eder and others suggest that ultrasound may be a useful tool for earlier diagnosis of PsA. Ultrasound is more sensitive than a physical examination and can detect inflammation in joints and entheses, she noted. Another effective method may be more systematic use of screening questionnaires, Dr. Coates said, or simply more systematic questioning of patients.
“Questionnaires are not a high priority for a primary care physician who may have only a few patients with psoriasis. Even some dermatologists may not use the questionnaires because they take time to administer and assess. But just asking a psoriasis patient whether they have joint symptoms is enough,” Dr. Eder said. All clinicians who encounter patients with psoriasis should ask about musculoskeletal symptoms and refer when appropriate to a rheumatologist, Dr. Reddy said.
The earliest indicators of PsA
Evidence supporting ultrasound’s value for early PsA diagnosis came in a report at the most recent annual meeting of the American College of Rheumatology in Chicago in October 2018. Researchers from the University of Rochester (New York) used ultrasound to examine 78 patients with psoriasis but without PsA or musculoskeletal symptoms and 25 healthy controls. They found ultrasound abnormalities in almost half of the patients with psoriasis, significantly more than in the controls (Thiele R et al. Arthritis Rheumatol. 2018;70[suppl 10]: Abstract 2904).
Another report at the ACR annual meeting last October looked at the incidence of physician visits for nonspecific musculoskeletal symptoms during each of the 5 years preceding diagnosis of PsA. A prior report from Dr. Eder and her associates had documented in an observational cohort of 410 patients with psoriasis that, prior to development of PsA, patients often had nonspecific musculoskeletal symptoms of joint pain, fatigue, and stiffness that constituted a “preclinical” phase (Arthritis Rheumatol. 2017 March;69[3]:622-9).
In October, Dr. Eder reported how the appearance of musculoskeletal symptoms played out in terms of physician visits. She and her associates analyzed data from an Ontario health insurance database that included about 430,000 Ontario patients seen by 466 primary care physicians, which included 462 patients with a new diagnosis of PsA and 2,310 matched controls. The results showed that, in every year during the 5 years preceding diagnosis of PsA, the patients who would wind up getting diagnosed had roughly twice the number of visits to a primary care physician each year for nonspecific musculoskeletal issues. A similar pattern of doubled visits occurred for people prior to their PsA diagnosis going to physicians who specialize in musculoskeletal conditions, and when the analysis focused on visits to rheumatologists, patients who went on to get diagnosed with PsA had a nearly sevenfold increased rate of these visits, compared with controls, for each of the 5 years preceding their PsA diagnosis (Eder L et al. Arthritis Rheumatol. 2018;70[suppl 10]: Abstract 967).
These results “highlight that in many patients PsA is not an acute disease that starts suddenly. In many patients, there is a period when the patient experiences musculoskeletal symptoms and sees a primary care physician or rheumatologist and may be diagnosed with something that is not PsA. That means that the delay in diagnosis [of PsA] may have happened because the patients were misdiagnosed. It reinforces the need for better diagnostic tools,” Dr. Eder said. “We have focused on getting these patients to see a rheumatologist earlier, but that may not be enough. These patients may not receive routine follow-up; we need to do more follow-up on patients like these.” Diagnosing PsA early means earlier treatment, a better chance of reaching remission, less chance of permanent joint damage, and better quality of life.
The challenges of making an early diagnosis were also documented in a study reported by Dr. Ogdie during the June 2018 annual congress of the European League Against Rheumatism. Dr. Ogdie reported on the survey responses of 203 patients who said they had been diagnosed with PsA whose index diagnosis was a median of 6 years before they completed the survey. A total of 195 of these patients, or 96%, said that they had received at least one misdiagnosis prior to their PsA diagnosis (Odgie A et al. Ann Rheum Dis. 2018;77[Suppl 2]:163. Abstract THU0292). The most common misdiagnoses were psychosomatic disease, reported by 27% of the patients; osteoarthritis in 22%; anxiety or depression in 18%; and an orthopedic problem in 18%. (Patients could report more than one type of misdiagnosis.)
The results “showed that patients often had substantial delays and misdiagnoses before they received a PsA diagnosis,” Dr. Ogdie and her associates concluded. Although the CASPAR classification criteria may be the agreed on PsA definition, recent findings suggest a pre-PsA stage exists with musculoskeletal and other abnormalities. “How may we diagnose ‘pre-PsA’? How might we capture this transition phase from psoriasis to PsA before the CASPAR criteria are fulfilled,” she wondered in an interview. “If we could stop PsA before it is clinically relevant, that could dramatically change the course of the disease. This is a big need in the field right now.”
Weight loss and other interventions
Aside from treating psoriasis and perhaps putting a patient with psoriasis in a PsA-prevention trial, one of the best ways to prevent PsA may be weight loss.
Results from “some studies suggest that being overweight increases the risk for developing PsA. Obesity also exacerbates skin psoriasis, makes treatment less effective, and further increases the risk of cardiometabolic diseases associated with psoriasis,” Dr. Gelfand said. “All patients with psoriatic disease should be educated about the importance of maintaining a healthy body weight.”
“Several studies suggest that obesity is a risk factor for developing PsA. Obesity likely plays a role in driving or contributing to inflammation in psoriatic disease,” said Dr. Reddy, who noted that other PsA risk factors include nail psoriasis and first-degree relatives with PsA. Dr. Ogdie also cited uveitis and prior joint trauma as other risk factors.
“Strong observational data link obesity and PsA incidence. I talk to psoriasis patients about weight control, and selected patients could even consider bariatric surgery,” Dr. Eder said. Losing at least 5% of body mass index can make a difference, she added.
At the 2018 annual meeting of the American College of Rheumatology, researchers from the University of Bath (England) reported results from a retrospective, observational study of more than 90,000 people with recent-onset psoriasis; they found that people with an obese BMI had twice the rate of progression to PsA when compared with people with a normal BMI. Overweight people had a nearly 80% higher rate of incident PsA (Green A et al. Arthritis Rheumatol. 2018;70[Suppl 10]: Abstract 2134).
Hints have also emerged that new approaches to treating psoriasis also could help to keep PsA precursors at bay. One recent example from researchers at the University of Leeds (England) was a phase 2 study of 73 patients with moderate to severe psoriasis but no PsA who underwent ultrasound screening of their entheses for signs of inflammatory changes. The 23 patients underwent 52 weeks of treatment with the drug ustekinumab (Stelara), an antagonist of interleukin-12 and -23 that is approved for U.S. marketing to treat both psoriasis and PsA. After 24 weeks on treatment, their mean inflammation scores had dropped by more than 40%, and the effect persisted through 52 weeks of treatment (Arthritis Rheum. 2018 Nov 22. doi: 10.1002/art.40778).
Despite this promise, the researchers “haven’t looked long enough or in enough people to see whether this actually stops patients from developing PsA,” Dr. Coates commented. It also remains unclear whether this or another ultrasound abnormality detectable in joints or entheses is a reliable predictor of PsA, she noted.
“We still have a lot to learn about how to classify patients as high risk” for PsA, Dr. Ogdie concluded.
Dr. Eder has received research and educational grants from AbbVie, Amgen, Celgene, Lilly, Novartis, and UCB. Dr. Coates has received honoraria, research funding, or both from more than a dozen companies. Dr. Reddy has been a consultant to AbbVie, Novartis, Pfizer, and UCB. Dr. Merola has been a consultant to AbbVie, Celgene, GlaxoSmithKline, Janssen, Lilly, Novartis, Samumed, Sanofi, and UCB and has received research grants from Aclaris, Biogen, Incyte, Novartis, Pfizer, and Sanofi. Dr. Gelfand has been a consultant, adviser, or both to more than a dozen companies. Dr. Ogdie has been a consultant to AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Corrona, Lilly, Novartis, Pfizer, and Takeda.
Most patients with psoriatic arthritis first present with psoriasis only. Their skin disorder precedes any joint involvement, often by several years. That suggests targeting interventions to patients with psoriasis to prevent or slow their progression to psoriatic arthritis, as well as following psoriatic patients closely to diagnose psoriatic arthritis quickly when it first appears. It’s a simple and attractive management premise that’s been challenging to apply in practice.
It’s not that clinicians aren’t motivated to diagnose psoriatic arthritis (PsA) in patients early, hopefully as soon as it appears. The susceptibility of patients with psoriasis to develop PsA is well described, with an annual progression rate of about 3%, and adverse consequences result from even a 6-month delay in diagnosis.
“Some physicians still don’t ask psoriasis patients about joint pain, or their symptoms are misinterpreted as something else,” said Lihi Eder, MD, a rheumatologist at Women’s College Research Institute, Toronto, and the University of Toronto. “Although there is increased awareness about PsA, there are still delays in diagnosis,” she said in an interview.
“Often there is a massive delay in diagnosis, and we know from a number of studies that longer duration of symptoms before diagnosis is associated with poorer outcomes,” said Laura C. Coates, MBChB, PhD, a rheumatologist at the University of Oxford (England). The delay to PsA diagnosis is generally “longer than for equivalent rheumatoid arthritis patients. PsA patients take longer to ask a primary care physician for help, longer to get a referral to a rheumatologist, and longer to get a diagnosis” from a rheumatologist. “We need to educate patients with psoriasis about their risk so that they seek help, educate GPs about whom to refer, and educate rheumatologists about diagnosis,” Dr. Coates said.
“It is very important to diagnose PsA as early as possible. We know that a delay in diagnosis and treatment can lead to worse outcomes and joint damage,” said Soumya M. Reddy, MD, codirector of the Psoriasis and Psoriatic Arthritis Center at New York University Langone Health in New York. “The heterogeneity of clinical manifestations of PsA can make it difficult to diagnose, and in some cases this leads to delayed diagnosis.”
“We are increasingly interested in the concept of preventing PsA. Psoriasis is a unique disease state in which we have an at-risk population where 30% will develop an inflammatory and potentially damaging arthritis. This may become important as our skin treatments may also treat musculoskeletal components of the disease,” said Joseph F. Merola, MD, director of the Center for Skin and Related Musculoskeletal Diseases at Brigham and Women’s Hospital in Boston and double board certified in dermatology and rheumatology.
Focusing on patients with psoriasis
Treatment of psoriasis makes sense to address several quality-of-life issues, but controlling the severity of psoriatic skin manifestations gives patients no guarantees about their possible progression to PsA.
“So many people have mild psoriasis that, although they are less likely, proportionately, to get PsA, we still see many in the clinic,” said Dr. Coates. “Patients with severe skin involvement have a good reason to get treatment, which could help test whether a drug slows progression to arthritis. But it’s unethical to not treat severe psoriasis just to have a comparison group.” Aside from skin psoriasis, “we don’t have any other good markers,” Dr. Coates noted.
PsA can develop in patients who had psoriasis in the past but without currently active disease. “At the level of individual patients you can’t say someone is protected from developing PsA because their psoriasis is inactive,” Dr. Eder said. “No study has looked at whether treatment of psoriasis reduces the risk for progression to PsA. We don’t know whether any treatments that reduce inflammation in psoriasis also reduce progression to PsA.” Regardless, treating psoriasis is important because it improves quality of life and may have a beneficial, long-term effects on possible cardiovascular disease effects from psoriasis, Dr. Eder said.
Her research group is now studying the associations among different biological drugs taken by patients with psoriasis and their subsequent incidence of PsA with use of medical records from about 4 million Israeli residents. Other studies are also looking at this, but they are all observational and therefore are subject to unidentified confounders, she noted. A more definitive demonstration of PsA protection would need a randomized trial.
“The idea of preventing the transition from psoriasis to PsA is an exciting concept. But currently, there are no established treatments for preventing transition of psoriasis to PsA. It’s an area of active research, and the holy grail of psoriatic disease research. We do not yet know whether successful treatment of skin psoriasis delays the onset of arthritis,” Dr. Reddy said in an interview.
“The risk of developing PsA increases as the severity of skin psoriasis increases, measured by percentage of body surface area affected. However, there is only a weak correlation between the severity of skin disease and the severity of PsA,” said Joel M. Gelfand, MD, professor of dermatology at the University of Pennsylvania in Philadelphia.
Widening the PsA diagnostic net
What’s elusive is some other parameter to identify the 3% of psoriasis patients who will develop PsA during the next year – or at least a better way to find patients as soon as they have what is identifiably PsA.
The diagnostic definition for PsA that many experts now accept is actually a set of classification criteria, CASPAR (Classification Criteria for Psoriatic Arthritis) (Arthritis Rheum. 2006 Aug;54[8]:2665-73). But in actual practice, diagnosing PsA relies heavily on clinical skill, case recognition, and ruling out mimickers.
“The CASPAR criteria were developed as classification criteria to use in studies, but they are also quite helpful in diagnosing PsA. It is the agreed on definition of PsA at the moment,” said Alexis Ogdie, MD, director of the psoriatic arthritis clinic at the University of Pennsylvania.
“CASPAR fills the role at present for clinical trials, but the diagnosis remains clinical, based on history, physical findings, and supported by lab and radiology findings,” Dr. Merola said. “A clinical prediction tool and a proper biomarker would be of great value.”
“We certainly use CASPAR criteria in the clinic, but they do not include all PsA patients; sometimes we diagnose PsA in patients who don’t meet the CASPAR criteria,” Dr. Coates said.
“In practice, rheumatologists mostly use their clinical judgment: a patient with history and findings typical of PsA after ruling out other causes. But distinguishing inflammatory from noninflammatory arthritis – like osteoarthritis or fibromyalgia – can be quite difficult; that’s the main challenge,” Dr. Eder said. “Rheumatologists rely on their clinical skill and experience. PsA can be difficult to diagnose. There is no biomarker for it. PsA is complex [to diagnose], and that’s why it’s diagnosed later. A primary care physician might get a negative result on a rheumatoid factor test and think that rules out PsA, but it doesn’t.”
Dr. Eder and others suggest that ultrasound may be a useful tool for earlier diagnosis of PsA. Ultrasound is more sensitive than a physical examination and can detect inflammation in joints and entheses, she noted. Another effective method may be more systematic use of screening questionnaires, Dr. Coates said, or simply more systematic questioning of patients.
“Questionnaires are not a high priority for a primary care physician who may have only a few patients with psoriasis. Even some dermatologists may not use the questionnaires because they take time to administer and assess. But just asking a psoriasis patient whether they have joint symptoms is enough,” Dr. Eder said. All clinicians who encounter patients with psoriasis should ask about musculoskeletal symptoms and refer when appropriate to a rheumatologist, Dr. Reddy said.
The earliest indicators of PsA
Evidence supporting ultrasound’s value for early PsA diagnosis came in a report at the most recent annual meeting of the American College of Rheumatology in Chicago in October 2018. Researchers from the University of Rochester (New York) used ultrasound to examine 78 patients with psoriasis but without PsA or musculoskeletal symptoms and 25 healthy controls. They found ultrasound abnormalities in almost half of the patients with psoriasis, significantly more than in the controls (Thiele R et al. Arthritis Rheumatol. 2018;70[suppl 10]: Abstract 2904).
Another report at the ACR annual meeting last October looked at the incidence of physician visits for nonspecific musculoskeletal symptoms during each of the 5 years preceding diagnosis of PsA. A prior report from Dr. Eder and her associates had documented in an observational cohort of 410 patients with psoriasis that, prior to development of PsA, patients often had nonspecific musculoskeletal symptoms of joint pain, fatigue, and stiffness that constituted a “preclinical” phase (Arthritis Rheumatol. 2017 March;69[3]:622-9).
In October, Dr. Eder reported how the appearance of musculoskeletal symptoms played out in terms of physician visits. She and her associates analyzed data from an Ontario health insurance database that included about 430,000 Ontario patients seen by 466 primary care physicians, which included 462 patients with a new diagnosis of PsA and 2,310 matched controls. The results showed that, in every year during the 5 years preceding diagnosis of PsA, the patients who would wind up getting diagnosed had roughly twice the number of visits to a primary care physician each year for nonspecific musculoskeletal issues. A similar pattern of doubled visits occurred for people prior to their PsA diagnosis going to physicians who specialize in musculoskeletal conditions, and when the analysis focused on visits to rheumatologists, patients who went on to get diagnosed with PsA had a nearly sevenfold increased rate of these visits, compared with controls, for each of the 5 years preceding their PsA diagnosis (Eder L et al. Arthritis Rheumatol. 2018;70[suppl 10]: Abstract 967).
These results “highlight that in many patients PsA is not an acute disease that starts suddenly. In many patients, there is a period when the patient experiences musculoskeletal symptoms and sees a primary care physician or rheumatologist and may be diagnosed with something that is not PsA. That means that the delay in diagnosis [of PsA] may have happened because the patients were misdiagnosed. It reinforces the need for better diagnostic tools,” Dr. Eder said. “We have focused on getting these patients to see a rheumatologist earlier, but that may not be enough. These patients may not receive routine follow-up; we need to do more follow-up on patients like these.” Diagnosing PsA early means earlier treatment, a better chance of reaching remission, less chance of permanent joint damage, and better quality of life.
The challenges of making an early diagnosis were also documented in a study reported by Dr. Ogdie during the June 2018 annual congress of the European League Against Rheumatism. Dr. Ogdie reported on the survey responses of 203 patients who said they had been diagnosed with PsA whose index diagnosis was a median of 6 years before they completed the survey. A total of 195 of these patients, or 96%, said that they had received at least one misdiagnosis prior to their PsA diagnosis (Odgie A et al. Ann Rheum Dis. 2018;77[Suppl 2]:163. Abstract THU0292). The most common misdiagnoses were psychosomatic disease, reported by 27% of the patients; osteoarthritis in 22%; anxiety or depression in 18%; and an orthopedic problem in 18%. (Patients could report more than one type of misdiagnosis.)
The results “showed that patients often had substantial delays and misdiagnoses before they received a PsA diagnosis,” Dr. Ogdie and her associates concluded. Although the CASPAR classification criteria may be the agreed on PsA definition, recent findings suggest a pre-PsA stage exists with musculoskeletal and other abnormalities. “How may we diagnose ‘pre-PsA’? How might we capture this transition phase from psoriasis to PsA before the CASPAR criteria are fulfilled,” she wondered in an interview. “If we could stop PsA before it is clinically relevant, that could dramatically change the course of the disease. This is a big need in the field right now.”
Weight loss and other interventions
Aside from treating psoriasis and perhaps putting a patient with psoriasis in a PsA-prevention trial, one of the best ways to prevent PsA may be weight loss.
Results from “some studies suggest that being overweight increases the risk for developing PsA. Obesity also exacerbates skin psoriasis, makes treatment less effective, and further increases the risk of cardiometabolic diseases associated with psoriasis,” Dr. Gelfand said. “All patients with psoriatic disease should be educated about the importance of maintaining a healthy body weight.”
“Several studies suggest that obesity is a risk factor for developing PsA. Obesity likely plays a role in driving or contributing to inflammation in psoriatic disease,” said Dr. Reddy, who noted that other PsA risk factors include nail psoriasis and first-degree relatives with PsA. Dr. Ogdie also cited uveitis and prior joint trauma as other risk factors.
“Strong observational data link obesity and PsA incidence. I talk to psoriasis patients about weight control, and selected patients could even consider bariatric surgery,” Dr. Eder said. Losing at least 5% of body mass index can make a difference, she added.
At the 2018 annual meeting of the American College of Rheumatology, researchers from the University of Bath (England) reported results from a retrospective, observational study of more than 90,000 people with recent-onset psoriasis; they found that people with an obese BMI had twice the rate of progression to PsA when compared with people with a normal BMI. Overweight people had a nearly 80% higher rate of incident PsA (Green A et al. Arthritis Rheumatol. 2018;70[Suppl 10]: Abstract 2134).
Hints have also emerged that new approaches to treating psoriasis also could help to keep PsA precursors at bay. One recent example from researchers at the University of Leeds (England) was a phase 2 study of 73 patients with moderate to severe psoriasis but no PsA who underwent ultrasound screening of their entheses for signs of inflammatory changes. The 23 patients underwent 52 weeks of treatment with the drug ustekinumab (Stelara), an antagonist of interleukin-12 and -23 that is approved for U.S. marketing to treat both psoriasis and PsA. After 24 weeks on treatment, their mean inflammation scores had dropped by more than 40%, and the effect persisted through 52 weeks of treatment (Arthritis Rheum. 2018 Nov 22. doi: 10.1002/art.40778).
Despite this promise, the researchers “haven’t looked long enough or in enough people to see whether this actually stops patients from developing PsA,” Dr. Coates commented. It also remains unclear whether this or another ultrasound abnormality detectable in joints or entheses is a reliable predictor of PsA, she noted.
“We still have a lot to learn about how to classify patients as high risk” for PsA, Dr. Ogdie concluded.
Dr. Eder has received research and educational grants from AbbVie, Amgen, Celgene, Lilly, Novartis, and UCB. Dr. Coates has received honoraria, research funding, or both from more than a dozen companies. Dr. Reddy has been a consultant to AbbVie, Novartis, Pfizer, and UCB. Dr. Merola has been a consultant to AbbVie, Celgene, GlaxoSmithKline, Janssen, Lilly, Novartis, Samumed, Sanofi, and UCB and has received research grants from Aclaris, Biogen, Incyte, Novartis, Pfizer, and Sanofi. Dr. Gelfand has been a consultant, adviser, or both to more than a dozen companies. Dr. Ogdie has been a consultant to AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Corrona, Lilly, Novartis, Pfizer, and Takeda.
Aleukemic leukemia cutis
On examination, the numerous firm, indurated nodules ranged in size from 1 to 4 cm. There was no palpable lymphadenopathy.
Results of a peripheral blood cell count showed the following:
- Hemoglobin 12.5 g/dL (reference range 13.0–17.0)
- Platelet count 154 × 109/L (130–400)
- White blood cell count 5.0 × 109/L (4.0–11.0)
- Neutrophils 1.7 × 109/L (1.5–8.0)
- Lymphocytes 2.2 × 109/L (1.0–4.0)
- Monocytes 1.0 × 109/L (0.2–1.0)
- Eosinophils 0 (0–0.4)
- Basophils 0 (0–0.2)
- Blasts 0.
The findings were consistent with leukemic cells with monocytic differentiation. The infiltrate was unusual because leukemic infiltrates typically demonstrate a high nuclear-to-cytoplasmic ratio, but in this case the malignant cells had moderate amounts of cytoplasm due to the monocytic differentiation. Also, a grenz zone is more typically seen in B-cell lymphomas, and T cells more typically demonstrate epidermotropism.
Bone marrow aspiration was performed and revealed a hypercellular bone marrow with trilineage maturation with only 2% blasts. The fluorescence in situ hybridization testing for myelodysplastic syndrome and acute myeloid leukemia was normal. A diagnosis of aleukemic leukemia cutis was made.
After 2 months of chemotherapy with azacitidine, the nodules were less indurated. Treatment was briefly withdrawn due to the development of acute pneumonia, leading to a rapid progression of cutaneous involvement. Despite restarting chemotherapy, the patient died.
ALEUKEMIC LEUKEMIA CUTIS
The differential diagnosis of leukemia cutis is diverse and extensive. Patients often present with painless, firm, indurated nodules, papules, and plaques.1 The lesions can be small, involving a small amount of body surface area, but can also be very large and diffuse.
In our patient’s case, there were no new drugs or exposures to suggest a drug-related eruption, or pruritus or pain to suggest an inflammatory process. The rapid progression of the lesions suggested either an infectious or malignant process. The top 3 conditions in the differential diagnosis, based on his clinical presentation, were cutaneous T-cell lymphoma, cutaneous CD30+ anaplastic large-cell lymphoma, and a drug-induced cutaneous pseudolymphoma.
Skin biopsy is required to differentiate leukemia cutis from the other conditions. On skin biopsy study, leukemia cutis is characterized by infiltration of the skin by leukemic cells and is seen in 10% to 15% of patients with acute myeloid leukemia.2 In 5% of cases, leukemia cutis can present without bone marrow or peripheral signs of leukemia, hence the term aleukemic leukemia cutis.3 Cutaneous signs can occur before, after, or simultaneously with systemic leukemia.4
In the absence of systemic symptoms, the diagnosis is made when progressive cutaneous symptoms are present. The prognosis for aleukemic leukemia cutis is poor. Prompt diagnosis with skin biopsy is paramount to improve outcomes.
Acknowledgment: We would like to recognize Maanasa Devabhaktuni for her assistance in reporting this case.
- Yonal I, Hindilerden F, Coskun R, Dogan OI, Nalcaci M. Aleukemic leukemia cutis manifesting with disseminated nodular eruptions and a plaque preceding acute monocytic leukemia: a case report. Case Rep Oncol 2011; 4(3):547–554. doi:10.1159/000334745
- Cho-Vega JH, Medeiros LJ, Prieto VG, Vega F. Leukemia cutis. Am J Clin Pathol 2008; 129(1):130–142. doi:10.1309/WYACYWF6NGM3WBRT
- Kang YS, Kim HS, Park HJ, et al. Clinical characteristics of 75 patients with leukemia cutis. J Korean Med Sci 2013; 28(4):614–619. doi:10.3346/jkms.2013.28.4.614
- Obiozor C, Ganguly S, Fraga GR. Leukemia cutis with lymphoglandular bodies: a clue to acute lymphoblastic leukemia cutis. Dermatol Online J 2015; 21(8)pii:13030/qt6m18g35f. pmid:26437164
On examination, the numerous firm, indurated nodules ranged in size from 1 to 4 cm. There was no palpable lymphadenopathy.
Results of a peripheral blood cell count showed the following:
- Hemoglobin 12.5 g/dL (reference range 13.0–17.0)
- Platelet count 154 × 109/L (130–400)
- White blood cell count 5.0 × 109/L (4.0–11.0)
- Neutrophils 1.7 × 109/L (1.5–8.0)
- Lymphocytes 2.2 × 109/L (1.0–4.0)
- Monocytes 1.0 × 109/L (0.2–1.0)
- Eosinophils 0 (0–0.4)
- Basophils 0 (0–0.2)
- Blasts 0.
The findings were consistent with leukemic cells with monocytic differentiation. The infiltrate was unusual because leukemic infiltrates typically demonstrate a high nuclear-to-cytoplasmic ratio, but in this case the malignant cells had moderate amounts of cytoplasm due to the monocytic differentiation. Also, a grenz zone is more typically seen in B-cell lymphomas, and T cells more typically demonstrate epidermotropism.
Bone marrow aspiration was performed and revealed a hypercellular bone marrow with trilineage maturation with only 2% blasts. The fluorescence in situ hybridization testing for myelodysplastic syndrome and acute myeloid leukemia was normal. A diagnosis of aleukemic leukemia cutis was made.
After 2 months of chemotherapy with azacitidine, the nodules were less indurated. Treatment was briefly withdrawn due to the development of acute pneumonia, leading to a rapid progression of cutaneous involvement. Despite restarting chemotherapy, the patient died.
ALEUKEMIC LEUKEMIA CUTIS
The differential diagnosis of leukemia cutis is diverse and extensive. Patients often present with painless, firm, indurated nodules, papules, and plaques.1 The lesions can be small, involving a small amount of body surface area, but can also be very large and diffuse.
In our patient’s case, there were no new drugs or exposures to suggest a drug-related eruption, or pruritus or pain to suggest an inflammatory process. The rapid progression of the lesions suggested either an infectious or malignant process. The top 3 conditions in the differential diagnosis, based on his clinical presentation, were cutaneous T-cell lymphoma, cutaneous CD30+ anaplastic large-cell lymphoma, and a drug-induced cutaneous pseudolymphoma.
Skin biopsy is required to differentiate leukemia cutis from the other conditions. On skin biopsy study, leukemia cutis is characterized by infiltration of the skin by leukemic cells and is seen in 10% to 15% of patients with acute myeloid leukemia.2 In 5% of cases, leukemia cutis can present without bone marrow or peripheral signs of leukemia, hence the term aleukemic leukemia cutis.3 Cutaneous signs can occur before, after, or simultaneously with systemic leukemia.4
In the absence of systemic symptoms, the diagnosis is made when progressive cutaneous symptoms are present. The prognosis for aleukemic leukemia cutis is poor. Prompt diagnosis with skin biopsy is paramount to improve outcomes.
Acknowledgment: We would like to recognize Maanasa Devabhaktuni for her assistance in reporting this case.
On examination, the numerous firm, indurated nodules ranged in size from 1 to 4 cm. There was no palpable lymphadenopathy.
Results of a peripheral blood cell count showed the following:
- Hemoglobin 12.5 g/dL (reference range 13.0–17.0)
- Platelet count 154 × 109/L (130–400)
- White blood cell count 5.0 × 109/L (4.0–11.0)
- Neutrophils 1.7 × 109/L (1.5–8.0)
- Lymphocytes 2.2 × 109/L (1.0–4.0)
- Monocytes 1.0 × 109/L (0.2–1.0)
- Eosinophils 0 (0–0.4)
- Basophils 0 (0–0.2)
- Blasts 0.
The findings were consistent with leukemic cells with monocytic differentiation. The infiltrate was unusual because leukemic infiltrates typically demonstrate a high nuclear-to-cytoplasmic ratio, but in this case the malignant cells had moderate amounts of cytoplasm due to the monocytic differentiation. Also, a grenz zone is more typically seen in B-cell lymphomas, and T cells more typically demonstrate epidermotropism.
Bone marrow aspiration was performed and revealed a hypercellular bone marrow with trilineage maturation with only 2% blasts. The fluorescence in situ hybridization testing for myelodysplastic syndrome and acute myeloid leukemia was normal. A diagnosis of aleukemic leukemia cutis was made.
After 2 months of chemotherapy with azacitidine, the nodules were less indurated. Treatment was briefly withdrawn due to the development of acute pneumonia, leading to a rapid progression of cutaneous involvement. Despite restarting chemotherapy, the patient died.
ALEUKEMIC LEUKEMIA CUTIS
The differential diagnosis of leukemia cutis is diverse and extensive. Patients often present with painless, firm, indurated nodules, papules, and plaques.1 The lesions can be small, involving a small amount of body surface area, but can also be very large and diffuse.
In our patient’s case, there were no new drugs or exposures to suggest a drug-related eruption, or pruritus or pain to suggest an inflammatory process. The rapid progression of the lesions suggested either an infectious or malignant process. The top 3 conditions in the differential diagnosis, based on his clinical presentation, were cutaneous T-cell lymphoma, cutaneous CD30+ anaplastic large-cell lymphoma, and a drug-induced cutaneous pseudolymphoma.
Skin biopsy is required to differentiate leukemia cutis from the other conditions. On skin biopsy study, leukemia cutis is characterized by infiltration of the skin by leukemic cells and is seen in 10% to 15% of patients with acute myeloid leukemia.2 In 5% of cases, leukemia cutis can present without bone marrow or peripheral signs of leukemia, hence the term aleukemic leukemia cutis.3 Cutaneous signs can occur before, after, or simultaneously with systemic leukemia.4
In the absence of systemic symptoms, the diagnosis is made when progressive cutaneous symptoms are present. The prognosis for aleukemic leukemia cutis is poor. Prompt diagnosis with skin biopsy is paramount to improve outcomes.
Acknowledgment: We would like to recognize Maanasa Devabhaktuni for her assistance in reporting this case.
- Yonal I, Hindilerden F, Coskun R, Dogan OI, Nalcaci M. Aleukemic leukemia cutis manifesting with disseminated nodular eruptions and a plaque preceding acute monocytic leukemia: a case report. Case Rep Oncol 2011; 4(3):547–554. doi:10.1159/000334745
- Cho-Vega JH, Medeiros LJ, Prieto VG, Vega F. Leukemia cutis. Am J Clin Pathol 2008; 129(1):130–142. doi:10.1309/WYACYWF6NGM3WBRT
- Kang YS, Kim HS, Park HJ, et al. Clinical characteristics of 75 patients with leukemia cutis. J Korean Med Sci 2013; 28(4):614–619. doi:10.3346/jkms.2013.28.4.614
- Obiozor C, Ganguly S, Fraga GR. Leukemia cutis with lymphoglandular bodies: a clue to acute lymphoblastic leukemia cutis. Dermatol Online J 2015; 21(8)pii:13030/qt6m18g35f. pmid:26437164
- Yonal I, Hindilerden F, Coskun R, Dogan OI, Nalcaci M. Aleukemic leukemia cutis manifesting with disseminated nodular eruptions and a plaque preceding acute monocytic leukemia: a case report. Case Rep Oncol 2011; 4(3):547–554. doi:10.1159/000334745
- Cho-Vega JH, Medeiros LJ, Prieto VG, Vega F. Leukemia cutis. Am J Clin Pathol 2008; 129(1):130–142. doi:10.1309/WYACYWF6NGM3WBRT
- Kang YS, Kim HS, Park HJ, et al. Clinical characteristics of 75 patients with leukemia cutis. J Korean Med Sci 2013; 28(4):614–619. doi:10.3346/jkms.2013.28.4.614
- Obiozor C, Ganguly S, Fraga GR. Leukemia cutis with lymphoglandular bodies: a clue to acute lymphoblastic leukemia cutis. Dermatol Online J 2015; 21(8)pii:13030/qt6m18g35f. pmid:26437164
Mohs Micrographic Surgery in the VHA (FULL)
Skin cancer is one of the most prevalent conditions among VHA patients.1 One of the largest U.S. health care systems, the VHA serves more than 9 million veterans.2 In 2012, 4% of VHA patients had a diagnosis of keratinocyte carcinoma or actinic keratosis; 49,229 cases of basal cell carcinoma and 26,310 cases of squamous cell carcinoma were diagnosed.1 With an aging veteran population and the incidence of skin cancers expected to increase, the development of cost-effective ways to provide easily accessible skin cancer treatments has become a priority for the VHA.
National Comprehensive Cancer Network (NCCN) guidelines recommend 3 types of surgical treatment for localized keratinocyte carcinoma: local destruction, wide local excision (WLE), and Mohs micrographic surgery (MMS). Tumors at low risk for recurrence may be treated with local destruction or WLE, and tumors at high risk may be treated with WLE or MMS.3
Mohs micrographic surgery involves staged narrow-margin excision with intraoperative tumor mapping and complete circumferential peripheral and deep margin assessment (CCPDMA). With the Mohs surgeon acting as both surgeon and dermatopathologist, it is possible to provide intraoperative correlation with the tissue bed and immediate additional margin resection precisely where needed. Relative to WLE, MMS yields improved histopathologic clearance rates and lower 5-year recurrence rates. It also provides improved preservation of normal tissue, optimized aesthetic outcomes, and high patient satisfaction.4-7 All this is achieved in an outpatient setting with the patient under local anesthesia; therefore the cost of ambulatory surgical centers or hospital operating rooms are avoided.5,8,9
The NCCN recommends WLE for high-risk tumors only if CCPDMA can be achieved. However, CCPDMA requires specialized surgical technique, tissue orientation, and pathology and is not equivalent to standard WLE with routine surgical pathology. Even with intraoperative bread-loafed frozen section analysis, WLE does not achieve the 100% margin assessment obtained with MMS.
In 2012, the American Academy of Dermatology in collaboration with the American College of Mohs Surgery, the American Society for Dermatologic Surgery, and the American Society for Mohs Surgery developed the Mohs Appropriate Use Criteria,which are now widely used as part of the standard of care to determine which cases of skin cancer should be treated with MMS over other modalities.10 These criteria, which are based on both evidence and expert consensus, take into account tumor size, histology, location, and patient factors, such as immunosuppression.
Despite its established benefits, MMS has not been uniformly accessible to veterans seeking VHA care. In 2007, Karen and colleagues surveyed dermatology chiefs and staff dermatologists from 101 VHA hospitals to characterize veterans’ access to MMS and found MMS available at only 11 VHA sites in 9 states.11 Further, access within the VHA was not evenly distributed across the U.S.
The VHA often makes payments, under “non-VA medical care” or “fee-basis care,” to providers in the community for services that the VHA is otherwise unable to provide. In 2014, Congress passed the Veterans Access, Choice, and Accountability Act and established the Veterans Choice program.2,12 This program allows veterans to obtain medical services from providers outside the VHA, based on veteran wait time and place of residence.12 The goal is to improve access. The present authors distinguish between 2 types of care: there are fee-based referrals managed and tracked by the VHA physician and the Veterans Choice for care without the diagnosing physician involvement or knowledge. In addition to expanding treatment options, the act called for reform within the VHA to improve resources and infrastructure needed to provide the best care for the veteran patient population.2
The authors conducted a study to identify current availability of MMS within the VHA and to provide a 10-year update to the survey findings of Karen and colleagues.11 VHA facilities that offer MMS were surveyed to determine available resources and what is needed to provide MMS within the VHA. Also surveyed were VHA facilities that do not offer MMS to determine how VHA patients with skin cancer receive surgical care from non-VA providers or from other surgical specialties.
Related: Nivolumab Linked to Nephritis in Melanoma
Methods
This study, deemed exempt from review by the University of California San Francisco Institutional Review Board, was a survey of dermatology section and service chiefs across the VHA. Subjects were identified through conference calls with VHA dermatologists, searches of individual VHA websites, and requests on dermatology e-mail listservs and were invited by email to participate in the survey.
The Research Electronic Data Capture platform (REDCap; Vanderbilt University Medical Center) was used for survey creation, implementation, dissemination, and data storage. The survey had 6 sections: site information; MMS availability; Mohs surgeon, Mohs laboratory, and support staff; MMS care; patient referral; and Mohs surgeon recruitment.
Data were collected between June 20 and August 1, 2016. Collected VHA site information included name, location, description, and MMS availability. If MMS was available, data were collected on surgeon training and background, number of MMS cases in 2015, and facility and support staff. In addition, subjects rated statements about various aspects of care provided (eg, patient wait time, patient distance traveled) on a 6-point Likert scale: strongly disagree, moderately disagree, slightly disagree, slightly agree, moderately agree, or strongly agree. This section included both positive and negative statements.
If MMS was not available at the VHA site, data were collected on patient referrals, including location within or outside the VHA and patient use of the Veterans Choice program. Subjects also rated positive and negative statements about referral experiences on a Likert scale (eg, patient wait time, patient distance traveled).
Categorical data were summarized, means and standard deviations were calculated for nominal data, and data analysis was performed with Microsoft Excel (Redmond, WA).
Results
The authors identified and surveyed 74 dermatology service and section chiefs across the VHA. Of these chiefs, 52 (70.3%) completed the survey. Completed surveys represented 49 hospital sites and 3 community-based outpatient clinics (CBOCs), including an integrated community-based clinic-hospital.
Sites That Provided MMS
Of the 52 sites with a completed survey, 19 provided MMS. These 19 sites were in 13 states and the District of Columbia, and the majority were in major cities along the coasts. All 19 sites were hospital medical centers, not community-based outpatient clinics, and all provided MMS through the dermatology department. In 2015, an estimated 6,686 MMS cases were performed, or an average of 371 per site (range, 40-1,000 cases/site) or 4.9 MMS cases per day (range, 3-8). These 19 sites were divided by yearly volume: high (> 500 cases/y), medium (200-500 cases/y), and low (< 200 cases/y).
Physical Space. On average, each site used 2.89 patient rooms (SD, 1.1; range, 1-6) for MMS. The Table lists numbers of patient rooms based on case volume. 
The MMS laboratory was adjacent to the surgical suite at 18 of the MMS sites and in the same building as the surgical suite, but not next to it, at 1 site. For their samples, 11 sites used an automated staining method, 7 used hand staining, and 2 used other methods (1 site used both automated and hand staining). Fourteen sites used hematoxlyin-eosin only, 1 used toluidine blue only, 3 used both hematoxlyin-eosin and toluidine blue, and 1 used MART-1 (melanoma antigen recognized by T cells 1) with hematoxlyin-eosin.
Related: Systemic Therapy in Metastatic Melanoma
Mohs Micrographic Surgeons. Sites with higher case volumes had more Mohs surgeons and more Mohs surgeons with VA appointments (captured as “eighths” or fraction of 8/8 full-time equivalent [FTE]). Information on fellowships and professional memberships was available for 30 Mohs surgeons: Ten (33.3%) were trained in fellowships accredited by both the American College of Mohs Surgery (ACMS) and the Accreditation Council for Graduate Medical Education (ACGME), 8 (26.7%) were trained in ACMS-recognized fellowships only, 7 (23.3%) were trained at ACGME-accredited fellowships only, 2 (6.7%) were trained elsewhere, and 3 (10.0%) had training listed as “uncertain.”
The majority of Mohs surgeons were members of professional societies, and many were members of more than one. Of the 30 Mohs surgeons, 24 (80.0%) were ACMS members, 5 (16.7%) were members of the American Society of Mohs Surgery, and 22 (73.3%) were members of the American Society of Dermatologic Surgery. Twenty-five (89.3%) were affiliated with an academic program.
Of the 30 surgeons, 19 (63.3%) were VHA employees hired by eighths, with an average eighths of 3.9 (SD, 2.7), or 49% of a FTE. Data on these surgeons’ pay tables and tiers were insufficient (only 3 provided the information). Of the other 11 surgeons, 10 (33.3%) were contracted, and 1 (3.3%) volunteered without compensation.
Support Staff. Of the 19 MMS sites, 17 (89.5%) used 1 histotechnician, and 2 (10.5%) used more than 1. Ten sites (52.6%) hired histotechnicians as contractors, 8 (42.1%) as employees, and 1 (5.3%) on a fee basis. In general, sites with higher case volumes had more nursing and support staff. Thirteen sites (68.4%) participated in the training of dermatology residents, and 5 sites (26.3%) trained Mohs fellows.
Wait Time Estimate. The survey also asked for estimates of the average amount of time patients waited for MMS. Of the 19 sites, 8 (42.1%) reported a wait time of less than 1 month, 10 (52.6%) reported 2 to 6 months, and 1 (5.3%) reported 7 months to 1 year. Seventeen (89.5%) of the 19 sites had a grading or triage system for expediting certain cancer types. At 7 sites, cases were prioritized on the basis of physician assessment; at 3 sites, aggressive or invasive squamous cell carcinoma received priority; other sites gave priority to patients with melanoma, patients with carcinoma near the nose or eye, organ transplant recipients, and other immunosuppressed patients.
Sites That Did Not Provide MMS
Of the 52 sites with a completed survey, 33 (63.5%) did not provide on-site MMS. Of these 33 sites, 28 (84.8%) used purchased care to refer patients to fee-basis non-VA dermatologists. In addition, 30 sites (90.9%) had patients activate Veterans Choice. Three sites referred patients to VA sites in another VISN.
Surgeon Recruitment
Five sites (9.6%) had an unfilled Mohs micrographic surgeon position. The average FTE of these unfilled positions was 0.6. One position had been open for less than 6 months, and the other 4 for more than 1 year. All 5 respondents with unfilled positions strongly agreed with the statement, “The position is unfilled because the salary is not competitive with the local market.”
Assessment of Care Provided
Respondents at sites that provided MMS rated various aspects of care (Figure 1). 
Respondents from sites that purchased MMS care from non-VA medical care rated surgery availability and ease of patient follow-up (Figure 2). 
Related: Getting a Better Picture of Skin Cancer
Discussion
Skin cancer is highly prevalent in the veteran patient population, and each year treatment by the VHA requires considerable spending.1 The results of this cross-sectional survey characterize veterans’ access to MMS within the VHA and provide a 10-year update to the survey findings of Karen and colleagues.11 Compared with their study, this survey offers a more granular description of practices and facilities as well as comparisons of VHA care with care purchased from outside sources. In outlining the state of MMS care within the VHA, this study highlights progress made and provides the updated data needed for continued efforts to optimize care and resource allocation for patients who require MMS within the VHA.
Although the number of VHA sites that provide MMS has increased over the past 10 years—from 11 sites in 9 states in 2007 to 19 sites in 13 states now—it is important to note that access to MMS care highly depends on geographic location.11 The VHA sites that provide MMS are clustered in major cities along the coasts. Four states (California, Florida, New York, and Texas) had > 1 MMS site, whereas most other states did not have any. In addition, only 1 MMS site served all of the northwest U.S. To ensure the anonymity of survey respondents, the authors did not further characterize the regional distribution of MMS sites.
Despite the increase in MMS sites, the number of MMS cases performed within the VHA seemed to have decreased. An estimated 8,310 cases were performed within the VHA in 2006,which decreased to 6,686 in 2015.11 Although these are estimates, the number of VHA cases likely decreased because of a rise in purchased care. Reviewing VHA electronic health records, Yoon and colleagues found that 19,681 MMS cases were performed either within the VHA or at non-VA medical care sites in 2012.1 Although the proportions of MMS cases performed within and outside the VHA were not reported, clearly many veterans had MMS performed through the VHA in recent years, and a high percentage of these cases were external referrals. More study is needed to further characterize MMS care within the VHA and MMS care purchased.
The 19 sites that provided MMS were evenly divided by volume: high (> 500 cases/y), medium (200-500 cases/y), and low (< 200 cases/y). Case volume correlated with the numbers of surgeons, nurses, and support staff at each site. Number of patient rooms dedicated to MMS at each site was not correlated with case volume; however, not ascertaining the number of days per week MMS was performed may have contributed to the lack of observed correlation.The majority of Mohs surgeons (25; 89.3%) within the VHA were affiliated with academic programs, which may partly explain the uneven geographic distribution of VHA sites that provide MMS (dermatology residency programs typically are in larger cities). The majority of Mohs surgeons were fellowship-trained through the ACMS or the ACGME. As the ACGME first began accrediting fellowship programs in 2003, younger surgeons were more likely to have completed this fellowship. According to respondents from sites that did not provide MMS, noncompetitive VHA salaries might be a barrier to Mohs surgeon recruitment. If a shift to providing more MMS care within the VHA were desired, an effective strategy could be to raise surgeon salaries. Higher salaries would bring in more Mohs surgeons and thereby yield higher MMS case volumes at VHA sites.
However, whether MMS is best provided for veterans within the VHA or at outside sites through referrals warrants further study. More than 60% of sites provided access to MMS through purchased care, either by fee-basis/non-VA medical care referrals or by the patient-elected Veterans Choice program. According to 84.2% of respondents at MMS sites and 66.7% of respondents at non-MMS sites, patients received care within a reasonable amount of time. In addition, respondents at MMS sites estimated longer patient travel distance for surgery. Respondents reported being concerned about coordination of care and follow-up for patients who received MMS outside the VHA. Other than referrals to outside sites for MMS, current triage practices include referral to other surgical specialties within the VHA, predominantly ear, nose, and throat and plastic surgery, for WLE. Given that access to on-site MMS varies significantly by geographic location, on-site MMS may be preferable in some locations, and external referrals in others. Based on this study's findings, on-site MMS seems superior to external referrals in all respects except patient travel distance. More research is needed to determine the most cost-effective triage practices. One option would be to have each VISN develop a skin cancer care center of excellence that would assist providers in appropriate triage and management.
Limitations
A decade has passed since Karen and colleagues conducted their study on MMS within the VHA.11 Data from this study suggest some progress has been made in improving veterans’ access to MMS. However, VHA sites that provide MMS are still predominantly located in large cities. In cases in which VHA providers refer patients to outside facilities, care coordination and follow-up are challenging. The present findings provide a basis for continuing VHA efforts to optimize resource allocation and improve longitudinal care for veterans who require MMS for skin cancer. Another area of interest is the comparative cost-effectiveness of MMS care provided within the VHA rather than at outside sites through purchased care. The answer may depend on geographic location, as MMS demand may be higher in some regions than that of others. For patients who receive MMS care outside the VHA, efforts should be made to improve communication and follow-up between VHA and external providers.
This study was limited in that it surveyed only those VHA sites with dermatology services or sections. It is possible, though unlikely, that MMS also was provided through nondermatology services. This study’s 70.3% response rate (52/74 dermatology chiefs) matched that of Karen and colleagues.11 Nevertheless, given that 30% of the surveyed chiefs did not respond and that analysis was performed separately for 2 small subgroups, (19 VHA sites that provided on-site MMS and 33 VHA sites that did not), the present findings may not be representative of the VHA as a whole.
Another limitation was that the survey captured respondent estimates of surgical caseloads and resources. Confirmation of these estimates would require a review of internal medical records and workforce analyses, which was beyond the scope of this study.
Conclusion
Although some progress has been made over the past 10 years, access to MMS within the VHA remains limited. About one-third of VHA sites provide on-site MMS; the other two-thirds refer patients with skin cancer to MMS sites outside the VHA. According to their dermatology chiefs, VHA sites that provide MMS have adequate resources and staffing and acceptable wait times for surgery; the challenge is in patients’ long travel distances. At sites that do not provide MMS, patients have access to MMS as well, and acceptable wait times and travel distances; the challenge is in follow-up, especially with activation of the Veterans Choice program. Studies should focus on standardizing veterans’ care and improving their access to MMS.
Click here to read the digital edition.
1. Yoon J, Phibbs CS, Chow A, Pomerantz H, Weinstock MA. Costs of keratinocyte carcinoma (nonmelanoma skin cancer) and actinic keratosis treatment in the Veterans Health Administration. Dermatol Surg. 2016;42(9):1041-1047.
2. Giroir BP, Wilensky GR. Reforming the Veterans Health Administration—beyond palliation of symptoms. N Engl J Med. 2015;373(18):1693-1695.
3. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Basal Cell Skin Cancer 1.2018. https://www.nccn.org/professionals/physician_gls/pdf/nmsc.pdf. Updated September 18, 2017. Accessed January 31, 2018.
4. Chren MM, Sahay AP, Bertenthal DS, Sen S, Landefeld CS. Quality-of-life outcomes of treatments for cutaneous basal cell carcinoma and squamous cell carcinoma. J Invest Dermatol. 2007;127(6):1351-1357.
5. Cook J, Zitelli JA. Mohs micrographic surgery: a cost analysis. J Am Acad Dermatol. 1998;39(5, pt 1):698-703.
6. Kauvar AN, Arpey CJ, Hruza G, Olbricht SM, Bennett R, Mahmoud BH. Consensus for nonmelanoma skin cancer treatment, part ii: squamous cell carcinoma, including a cost analysis of treatment methods. Dermatol Surg. 2015;41(11):1214-1240.
7. Kauvar AN, Cronin T Jr, Roenigk R, Hruza G, Bennett R; American Society for Dermatologic Surgery. Consensus for nonmelanoma skin cancer treatment: basal cell carcinoma, including a cost analysis of treatment methods. Dermatol Surg. 2015;41(5):550-571.
8. Chen JT, Kempton SJ, Rao VK. The economics of skin cancer: an analysis of Medicare payment data. Plast Reconstr Surg Glob Open. 2016;4(9):e868.
9. Tierney EP, Hanke CW. Cost effectiveness of Mohs micrographic surgery: review of the literature. J Drugs Dermatol. 2009;8(10):914-922.
10. Ad Hoc Task Force, Connolly SM, Baker DR, Coldiron BM, et al. AAD/ACMS/ASDSA/ASMS 2012 appropriate use criteria for Mohs micrographic surgery: a report of the American Academy of Dermatology, American College of Mohs Surgery, American Society for Dermatologic Surgery Association, and the American Society for Mohs Surgery. J Am Acad Dermatol. 2012;67(4):531-550.
11. Karen JK, Hale EK, Nehal KS, Levine VJ. Use of Mohs surgery by the Veterans Affairs Health Care System. J Am Acad Dermatol. 2009;60(6):1069-1070.
12. U.S. Department of Veterans Affairs. Expanded access to non-VA care through the Veterans Choice program. Interim final rule. Fed Regist. 2015;80(230):74991-74996.
Skin cancer is one of the most prevalent conditions among VHA patients.1 One of the largest U.S. health care systems, the VHA serves more than 9 million veterans.2 In 2012, 4% of VHA patients had a diagnosis of keratinocyte carcinoma or actinic keratosis; 49,229 cases of basal cell carcinoma and 26,310 cases of squamous cell carcinoma were diagnosed.1 With an aging veteran population and the incidence of skin cancers expected to increase, the development of cost-effective ways to provide easily accessible skin cancer treatments has become a priority for the VHA.
National Comprehensive Cancer Network (NCCN) guidelines recommend 3 types of surgical treatment for localized keratinocyte carcinoma: local destruction, wide local excision (WLE), and Mohs micrographic surgery (MMS). Tumors at low risk for recurrence may be treated with local destruction or WLE, and tumors at high risk may be treated with WLE or MMS.3
Mohs micrographic surgery involves staged narrow-margin excision with intraoperative tumor mapping and complete circumferential peripheral and deep margin assessment (CCPDMA). With the Mohs surgeon acting as both surgeon and dermatopathologist, it is possible to provide intraoperative correlation with the tissue bed and immediate additional margin resection precisely where needed. Relative to WLE, MMS yields improved histopathologic clearance rates and lower 5-year recurrence rates. It also provides improved preservation of normal tissue, optimized aesthetic outcomes, and high patient satisfaction.4-7 All this is achieved in an outpatient setting with the patient under local anesthesia; therefore the cost of ambulatory surgical centers or hospital operating rooms are avoided.5,8,9
The NCCN recommends WLE for high-risk tumors only if CCPDMA can be achieved. However, CCPDMA requires specialized surgical technique, tissue orientation, and pathology and is not equivalent to standard WLE with routine surgical pathology. Even with intraoperative bread-loafed frozen section analysis, WLE does not achieve the 100% margin assessment obtained with MMS.
In 2012, the American Academy of Dermatology in collaboration with the American College of Mohs Surgery, the American Society for Dermatologic Surgery, and the American Society for Mohs Surgery developed the Mohs Appropriate Use Criteria,which are now widely used as part of the standard of care to determine which cases of skin cancer should be treated with MMS over other modalities.10 These criteria, which are based on both evidence and expert consensus, take into account tumor size, histology, location, and patient factors, such as immunosuppression.
Despite its established benefits, MMS has not been uniformly accessible to veterans seeking VHA care. In 2007, Karen and colleagues surveyed dermatology chiefs and staff dermatologists from 101 VHA hospitals to characterize veterans’ access to MMS and found MMS available at only 11 VHA sites in 9 states.11 Further, access within the VHA was not evenly distributed across the U.S.
The VHA often makes payments, under “non-VA medical care” or “fee-basis care,” to providers in the community for services that the VHA is otherwise unable to provide. In 2014, Congress passed the Veterans Access, Choice, and Accountability Act and established the Veterans Choice program.2,12 This program allows veterans to obtain medical services from providers outside the VHA, based on veteran wait time and place of residence.12 The goal is to improve access. The present authors distinguish between 2 types of care: there are fee-based referrals managed and tracked by the VHA physician and the Veterans Choice for care without the diagnosing physician involvement or knowledge. In addition to expanding treatment options, the act called for reform within the VHA to improve resources and infrastructure needed to provide the best care for the veteran patient population.2
The authors conducted a study to identify current availability of MMS within the VHA and to provide a 10-year update to the survey findings of Karen and colleagues.11 VHA facilities that offer MMS were surveyed to determine available resources and what is needed to provide MMS within the VHA. Also surveyed were VHA facilities that do not offer MMS to determine how VHA patients with skin cancer receive surgical care from non-VA providers or from other surgical specialties.
Related: Nivolumab Linked to Nephritis in Melanoma
Methods
This study, deemed exempt from review by the University of California San Francisco Institutional Review Board, was a survey of dermatology section and service chiefs across the VHA. Subjects were identified through conference calls with VHA dermatologists, searches of individual VHA websites, and requests on dermatology e-mail listservs and were invited by email to participate in the survey.
The Research Electronic Data Capture platform (REDCap; Vanderbilt University Medical Center) was used for survey creation, implementation, dissemination, and data storage. The survey had 6 sections: site information; MMS availability; Mohs surgeon, Mohs laboratory, and support staff; MMS care; patient referral; and Mohs surgeon recruitment.
Data were collected between June 20 and August 1, 2016. Collected VHA site information included name, location, description, and MMS availability. If MMS was available, data were collected on surgeon training and background, number of MMS cases in 2015, and facility and support staff. In addition, subjects rated statements about various aspects of care provided (eg, patient wait time, patient distance traveled) on a 6-point Likert scale: strongly disagree, moderately disagree, slightly disagree, slightly agree, moderately agree, or strongly agree. This section included both positive and negative statements.
If MMS was not available at the VHA site, data were collected on patient referrals, including location within or outside the VHA and patient use of the Veterans Choice program. Subjects also rated positive and negative statements about referral experiences on a Likert scale (eg, patient wait time, patient distance traveled).
Categorical data were summarized, means and standard deviations were calculated for nominal data, and data analysis was performed with Microsoft Excel (Redmond, WA).
Results
The authors identified and surveyed 74 dermatology service and section chiefs across the VHA. Of these chiefs, 52 (70.3%) completed the survey. Completed surveys represented 49 hospital sites and 3 community-based outpatient clinics (CBOCs), including an integrated community-based clinic-hospital.
Sites That Provided MMS
Of the 52 sites with a completed survey, 19 provided MMS. These 19 sites were in 13 states and the District of Columbia, and the majority were in major cities along the coasts. All 19 sites were hospital medical centers, not community-based outpatient clinics, and all provided MMS through the dermatology department. In 2015, an estimated 6,686 MMS cases were performed, or an average of 371 per site (range, 40-1,000 cases/site) or 4.9 MMS cases per day (range, 3-8). These 19 sites were divided by yearly volume: high (> 500 cases/y), medium (200-500 cases/y), and low (< 200 cases/y).
Physical Space. On average, each site used 2.89 patient rooms (SD, 1.1; range, 1-6) for MMS. The Table lists numbers of patient rooms based on case volume.
The MMS laboratory was adjacent to the surgical suite at 18 of the MMS sites and in the same building as the surgical suite, but not next to it, at 1 site. For their samples, 11 sites used an automated staining method, 7 used hand staining, and 2 used other methods (1 site used both automated and hand staining). Fourteen sites used hematoxlyin-eosin only, 1 used toluidine blue only, 3 used both hematoxlyin-eosin and toluidine blue, and 1 used MART-1 (melanoma antigen recognized by T cells 1) with hematoxlyin-eosin.
Related: Systemic Therapy in Metastatic Melanoma
Mohs Micrographic Surgeons. Sites with higher case volumes had more Mohs surgeons and more Mohs surgeons with VA appointments (captured as “eighths” or fraction of 8/8 full-time equivalent [FTE]). Information on fellowships and professional memberships was available for 30 Mohs surgeons: Ten (33.3%) were trained in fellowships accredited by both the American College of Mohs Surgery (ACMS) and the Accreditation Council for Graduate Medical Education (ACGME), 8 (26.7%) were trained in ACMS-recognized fellowships only, 7 (23.3%) were trained at ACGME-accredited fellowships only, 2 (6.7%) were trained elsewhere, and 3 (10.0%) had training listed as “uncertain.”
The majority of Mohs surgeons were members of professional societies, and many were members of more than one. Of the 30 Mohs surgeons, 24 (80.0%) were ACMS members, 5 (16.7%) were members of the American Society of Mohs Surgery, and 22 (73.3%) were members of the American Society of Dermatologic Surgery. Twenty-five (89.3%) were affiliated with an academic program.
Of the 30 surgeons, 19 (63.3%) were VHA employees hired by eighths, with an average eighths of 3.9 (SD, 2.7), or 49% of a FTE. Data on these surgeons’ pay tables and tiers were insufficient (only 3 provided the information). Of the other 11 surgeons, 10 (33.3%) were contracted, and 1 (3.3%) volunteered without compensation.
Support Staff. Of the 19 MMS sites, 17 (89.5%) used 1 histotechnician, and 2 (10.5%) used more than 1. Ten sites (52.6%) hired histotechnicians as contractors, 8 (42.1%) as employees, and 1 (5.3%) on a fee basis. In general, sites with higher case volumes had more nursing and support staff. Thirteen sites (68.4%) participated in the training of dermatology residents, and 5 sites (26.3%) trained Mohs fellows.
Wait Time Estimate. The survey also asked for estimates of the average amount of time patients waited for MMS. Of the 19 sites, 8 (42.1%) reported a wait time of less than 1 month, 10 (52.6%) reported 2 to 6 months, and 1 (5.3%) reported 7 months to 1 year. Seventeen (89.5%) of the 19 sites had a grading or triage system for expediting certain cancer types. At 7 sites, cases were prioritized on the basis of physician assessment; at 3 sites, aggressive or invasive squamous cell carcinoma received priority; other sites gave priority to patients with melanoma, patients with carcinoma near the nose or eye, organ transplant recipients, and other immunosuppressed patients.
Sites That Did Not Provide MMS
Of the 52 sites with a completed survey, 33 (63.5%) did not provide on-site MMS. Of these 33 sites, 28 (84.8%) used purchased care to refer patients to fee-basis non-VA dermatologists. In addition, 30 sites (90.9%) had patients activate Veterans Choice. Three sites referred patients to VA sites in another VISN.
Surgeon Recruitment
Five sites (9.6%) had an unfilled Mohs micrographic surgeon position. The average FTE of these unfilled positions was 0.6. One position had been open for less than 6 months, and the other 4 for more than 1 year. All 5 respondents with unfilled positions strongly agreed with the statement, “The position is unfilled because the salary is not competitive with the local market.”
Assessment of Care Provided
Respondents at sites that provided MMS rated various aspects of care (Figure 1).
Respondents from sites that purchased MMS care from non-VA medical care rated surgery availability and ease of patient follow-up (Figure 2).
Related: Getting a Better Picture of Skin Cancer
Discussion
Skin cancer is highly prevalent in the veteran patient population, and each year treatment by the VHA requires considerable spending.1 The results of this cross-sectional survey characterize veterans’ access to MMS within the VHA and provide a 10-year update to the survey findings of Karen and colleagues.11 Compared with their study, this survey offers a more granular description of practices and facilities as well as comparisons of VHA care with care purchased from outside sources. In outlining the state of MMS care within the VHA, this study highlights progress made and provides the updated data needed for continued efforts to optimize care and resource allocation for patients who require MMS within the VHA.
Although the number of VHA sites that provide MMS has increased over the past 10 years—from 11 sites in 9 states in 2007 to 19 sites in 13 states now—it is important to note that access to MMS care highly depends on geographic location.11 The VHA sites that provide MMS are clustered in major cities along the coasts. Four states (California, Florida, New York, and Texas) had > 1 MMS site, whereas most other states did not have any. In addition, only 1 MMS site served all of the northwest U.S. To ensure the anonymity of survey respondents, the authors did not further characterize the regional distribution of MMS sites.
Despite the increase in MMS sites, the number of MMS cases performed within the VHA seemed to have decreased. An estimated 8,310 cases were performed within the VHA in 2006,which decreased to 6,686 in 2015.11 Although these are estimates, the number of VHA cases likely decreased because of a rise in purchased care. Reviewing VHA electronic health records, Yoon and colleagues found that 19,681 MMS cases were performed either within the VHA or at non-VA medical care sites in 2012.1 Although the proportions of MMS cases performed within and outside the VHA were not reported, clearly many veterans had MMS performed through the VHA in recent years, and a high percentage of these cases were external referrals. More study is needed to further characterize MMS care within the VHA and MMS care purchased.
The 19 sites that provided MMS were evenly divided by volume: high (> 500 cases/y), medium (200-500 cases/y), and low (< 200 cases/y). Case volume correlated with the numbers of surgeons, nurses, and support staff at each site. Number of patient rooms dedicated to MMS at each site was not correlated with case volume; however, not ascertaining the number of days per week MMS was performed may have contributed to the lack of observed correlation.The majority of Mohs surgeons (25; 89.3%) within the VHA were affiliated with academic programs, which may partly explain the uneven geographic distribution of VHA sites that provide MMS (dermatology residency programs typically are in larger cities). The majority of Mohs surgeons were fellowship-trained through the ACMS or the ACGME. As the ACGME first began accrediting fellowship programs in 2003, younger surgeons were more likely to have completed this fellowship. According to respondents from sites that did not provide MMS, noncompetitive VHA salaries might be a barrier to Mohs surgeon recruitment. If a shift to providing more MMS care within the VHA were desired, an effective strategy could be to raise surgeon salaries. Higher salaries would bring in more Mohs surgeons and thereby yield higher MMS case volumes at VHA sites.
However, whether MMS is best provided for veterans within the VHA or at outside sites through referrals warrants further study. More than 60% of sites provided access to MMS through purchased care, either by fee-basis/non-VA medical care referrals or by the patient-elected Veterans Choice program. According to 84.2% of respondents at MMS sites and 66.7% of respondents at non-MMS sites, patients received care within a reasonable amount of time. In addition, respondents at MMS sites estimated longer patient travel distance for surgery. Respondents reported being concerned about coordination of care and follow-up for patients who received MMS outside the VHA. Other than referrals to outside sites for MMS, current triage practices include referral to other surgical specialties within the VHA, predominantly ear, nose, and throat and plastic surgery, for WLE. Given that access to on-site MMS varies significantly by geographic location, on-site MMS may be preferable in some locations, and external referrals in others. Based on this study's findings, on-site MMS seems superior to external referrals in all respects except patient travel distance. More research is needed to determine the most cost-effective triage practices. One option would be to have each VISN develop a skin cancer care center of excellence that would assist providers in appropriate triage and management.
Limitations
A decade has passed since Karen and colleagues conducted their study on MMS within the VHA.11 Data from this study suggest some progress has been made in improving veterans’ access to MMS. However, VHA sites that provide MMS are still predominantly located in large cities. In cases in which VHA providers refer patients to outside facilities, care coordination and follow-up are challenging. The present findings provide a basis for continuing VHA efforts to optimize resource allocation and improve longitudinal care for veterans who require MMS for skin cancer. Another area of interest is the comparative cost-effectiveness of MMS care provided within the VHA rather than at outside sites through purchased care. The answer may depend on geographic location, as MMS demand may be higher in some regions than that of others. For patients who receive MMS care outside the VHA, efforts should be made to improve communication and follow-up between VHA and external providers.
This study was limited in that it surveyed only those VHA sites with dermatology services or sections. It is possible, though unlikely, that MMS also was provided through nondermatology services. This study’s 70.3% response rate (52/74 dermatology chiefs) matched that of Karen and colleagues.11 Nevertheless, given that 30% of the surveyed chiefs did not respond and that analysis was performed separately for 2 small subgroups, (19 VHA sites that provided on-site MMS and 33 VHA sites that did not), the present findings may not be representative of the VHA as a whole.
Another limitation was that the survey captured respondent estimates of surgical caseloads and resources. Confirmation of these estimates would require a review of internal medical records and workforce analyses, which was beyond the scope of this study.
Conclusion
Although some progress has been made over the past 10 years, access to MMS within the VHA remains limited. About one-third of VHA sites provide on-site MMS; the other two-thirds refer patients with skin cancer to MMS sites outside the VHA. According to their dermatology chiefs, VHA sites that provide MMS have adequate resources and staffing and acceptable wait times for surgery; the challenge is in patients’ long travel distances. At sites that do not provide MMS, patients have access to MMS as well, and acceptable wait times and travel distances; the challenge is in follow-up, especially with activation of the Veterans Choice program. Studies should focus on standardizing veterans’ care and improving their access to MMS.
Click here to read the digital edition.
Skin cancer is one of the most prevalent conditions among VHA patients.1 One of the largest U.S. health care systems, the VHA serves more than 9 million veterans.2 In 2012, 4% of VHA patients had a diagnosis of keratinocyte carcinoma or actinic keratosis; 49,229 cases of basal cell carcinoma and 26,310 cases of squamous cell carcinoma were diagnosed.1 With an aging veteran population and the incidence of skin cancers expected to increase, the development of cost-effective ways to provide easily accessible skin cancer treatments has become a priority for the VHA.
National Comprehensive Cancer Network (NCCN) guidelines recommend 3 types of surgical treatment for localized keratinocyte carcinoma: local destruction, wide local excision (WLE), and Mohs micrographic surgery (MMS). Tumors at low risk for recurrence may be treated with local destruction or WLE, and tumors at high risk may be treated with WLE or MMS.3
Mohs micrographic surgery involves staged narrow-margin excision with intraoperative tumor mapping and complete circumferential peripheral and deep margin assessment (CCPDMA). With the Mohs surgeon acting as both surgeon and dermatopathologist, it is possible to provide intraoperative correlation with the tissue bed and immediate additional margin resection precisely where needed. Relative to WLE, MMS yields improved histopathologic clearance rates and lower 5-year recurrence rates. It also provides improved preservation of normal tissue, optimized aesthetic outcomes, and high patient satisfaction.4-7 All this is achieved in an outpatient setting with the patient under local anesthesia; therefore the cost of ambulatory surgical centers or hospital operating rooms are avoided.5,8,9
The NCCN recommends WLE for high-risk tumors only if CCPDMA can be achieved. However, CCPDMA requires specialized surgical technique, tissue orientation, and pathology and is not equivalent to standard WLE with routine surgical pathology. Even with intraoperative bread-loafed frozen section analysis, WLE does not achieve the 100% margin assessment obtained with MMS.
In 2012, the American Academy of Dermatology in collaboration with the American College of Mohs Surgery, the American Society for Dermatologic Surgery, and the American Society for Mohs Surgery developed the Mohs Appropriate Use Criteria,which are now widely used as part of the standard of care to determine which cases of skin cancer should be treated with MMS over other modalities.10 These criteria, which are based on both evidence and expert consensus, take into account tumor size, histology, location, and patient factors, such as immunosuppression.
Despite its established benefits, MMS has not been uniformly accessible to veterans seeking VHA care. In 2007, Karen and colleagues surveyed dermatology chiefs and staff dermatologists from 101 VHA hospitals to characterize veterans’ access to MMS and found MMS available at only 11 VHA sites in 9 states.11 Further, access within the VHA was not evenly distributed across the U.S.
The VHA often makes payments, under “non-VA medical care” or “fee-basis care,” to providers in the community for services that the VHA is otherwise unable to provide. In 2014, Congress passed the Veterans Access, Choice, and Accountability Act and established the Veterans Choice program.2,12 This program allows veterans to obtain medical services from providers outside the VHA, based on veteran wait time and place of residence.12 The goal is to improve access. The present authors distinguish between 2 types of care: there are fee-based referrals managed and tracked by the VHA physician and the Veterans Choice for care without the diagnosing physician involvement or knowledge. In addition to expanding treatment options, the act called for reform within the VHA to improve resources and infrastructure needed to provide the best care for the veteran patient population.2
The authors conducted a study to identify current availability of MMS within the VHA and to provide a 10-year update to the survey findings of Karen and colleagues.11 VHA facilities that offer MMS were surveyed to determine available resources and what is needed to provide MMS within the VHA. Also surveyed were VHA facilities that do not offer MMS to determine how VHA patients with skin cancer receive surgical care from non-VA providers or from other surgical specialties.
Related: Nivolumab Linked to Nephritis in Melanoma
Methods
This study, deemed exempt from review by the University of California San Francisco Institutional Review Board, was a survey of dermatology section and service chiefs across the VHA. Subjects were identified through conference calls with VHA dermatologists, searches of individual VHA websites, and requests on dermatology e-mail listservs and were invited by email to participate in the survey.
The Research Electronic Data Capture platform (REDCap; Vanderbilt University Medical Center) was used for survey creation, implementation, dissemination, and data storage. The survey had 6 sections: site information; MMS availability; Mohs surgeon, Mohs laboratory, and support staff; MMS care; patient referral; and Mohs surgeon recruitment.
Data were collected between June 20 and August 1, 2016. Collected VHA site information included name, location, description, and MMS availability. If MMS was available, data were collected on surgeon training and background, number of MMS cases in 2015, and facility and support staff. In addition, subjects rated statements about various aspects of care provided (eg, patient wait time, patient distance traveled) on a 6-point Likert scale: strongly disagree, moderately disagree, slightly disagree, slightly agree, moderately agree, or strongly agree. This section included both positive and negative statements.
If MMS was not available at the VHA site, data were collected on patient referrals, including location within or outside the VHA and patient use of the Veterans Choice program. Subjects also rated positive and negative statements about referral experiences on a Likert scale (eg, patient wait time, patient distance traveled).
Categorical data were summarized, means and standard deviations were calculated for nominal data, and data analysis was performed with Microsoft Excel (Redmond, WA).
Results
The authors identified and surveyed 74 dermatology service and section chiefs across the VHA. Of these chiefs, 52 (70.3%) completed the survey. Completed surveys represented 49 hospital sites and 3 community-based outpatient clinics (CBOCs), including an integrated community-based clinic-hospital.
Sites That Provided MMS
Of the 52 sites with a completed survey, 19 provided MMS. These 19 sites were in 13 states and the District of Columbia, and the majority were in major cities along the coasts. All 19 sites were hospital medical centers, not community-based outpatient clinics, and all provided MMS through the dermatology department. In 2015, an estimated 6,686 MMS cases were performed, or an average of 371 per site (range, 40-1,000 cases/site) or 4.9 MMS cases per day (range, 3-8). These 19 sites were divided by yearly volume: high (> 500 cases/y), medium (200-500 cases/y), and low (< 200 cases/y).
Physical Space. On average, each site used 2.89 patient rooms (SD, 1.1; range, 1-6) for MMS. The Table lists numbers of patient rooms based on case volume.
The MMS laboratory was adjacent to the surgical suite at 18 of the MMS sites and in the same building as the surgical suite, but not next to it, at 1 site. For their samples, 11 sites used an automated staining method, 7 used hand staining, and 2 used other methods (1 site used both automated and hand staining). Fourteen sites used hematoxlyin-eosin only, 1 used toluidine blue only, 3 used both hematoxlyin-eosin and toluidine blue, and 1 used MART-1 (melanoma antigen recognized by T cells 1) with hematoxlyin-eosin.
Related: Systemic Therapy in Metastatic Melanoma
Mohs Micrographic Surgeons. Sites with higher case volumes had more Mohs surgeons and more Mohs surgeons with VA appointments (captured as “eighths” or fraction of 8/8 full-time equivalent [FTE]). Information on fellowships and professional memberships was available for 30 Mohs surgeons: Ten (33.3%) were trained in fellowships accredited by both the American College of Mohs Surgery (ACMS) and the Accreditation Council for Graduate Medical Education (ACGME), 8 (26.7%) were trained in ACMS-recognized fellowships only, 7 (23.3%) were trained at ACGME-accredited fellowships only, 2 (6.7%) were trained elsewhere, and 3 (10.0%) had training listed as “uncertain.”
The majority of Mohs surgeons were members of professional societies, and many were members of more than one. Of the 30 Mohs surgeons, 24 (80.0%) were ACMS members, 5 (16.7%) were members of the American Society of Mohs Surgery, and 22 (73.3%) were members of the American Society of Dermatologic Surgery. Twenty-five (89.3%) were affiliated with an academic program.
Of the 30 surgeons, 19 (63.3%) were VHA employees hired by eighths, with an average eighths of 3.9 (SD, 2.7), or 49% of a FTE. Data on these surgeons’ pay tables and tiers were insufficient (only 3 provided the information). Of the other 11 surgeons, 10 (33.3%) were contracted, and 1 (3.3%) volunteered without compensation.
Support Staff. Of the 19 MMS sites, 17 (89.5%) used 1 histotechnician, and 2 (10.5%) used more than 1. Ten sites (52.6%) hired histotechnicians as contractors, 8 (42.1%) as employees, and 1 (5.3%) on a fee basis. In general, sites with higher case volumes had more nursing and support staff. Thirteen sites (68.4%) participated in the training of dermatology residents, and 5 sites (26.3%) trained Mohs fellows.
Wait Time Estimate. The survey also asked for estimates of the average amount of time patients waited for MMS. Of the 19 sites, 8 (42.1%) reported a wait time of less than 1 month, 10 (52.6%) reported 2 to 6 months, and 1 (5.3%) reported 7 months to 1 year. Seventeen (89.5%) of the 19 sites had a grading or triage system for expediting certain cancer types. At 7 sites, cases were prioritized on the basis of physician assessment; at 3 sites, aggressive or invasive squamous cell carcinoma received priority; other sites gave priority to patients with melanoma, patients with carcinoma near the nose or eye, organ transplant recipients, and other immunosuppressed patients.
Sites That Did Not Provide MMS
Of the 52 sites with a completed survey, 33 (63.5%) did not provide on-site MMS. Of these 33 sites, 28 (84.8%) used purchased care to refer patients to fee-basis non-VA dermatologists. In addition, 30 sites (90.9%) had patients activate Veterans Choice. Three sites referred patients to VA sites in another VISN.
Surgeon Recruitment
Five sites (9.6%) had an unfilled Mohs micrographic surgeon position. The average FTE of these unfilled positions was 0.6. One position had been open for less than 6 months, and the other 4 for more than 1 year. All 5 respondents with unfilled positions strongly agreed with the statement, “The position is unfilled because the salary is not competitive with the local market.”
Assessment of Care Provided
Respondents at sites that provided MMS rated various aspects of care (Figure 1).
Respondents from sites that purchased MMS care from non-VA medical care rated surgery availability and ease of patient follow-up (Figure 2).
Related: Getting a Better Picture of Skin Cancer
Discussion
Skin cancer is highly prevalent in the veteran patient population, and each year treatment by the VHA requires considerable spending.1 The results of this cross-sectional survey characterize veterans’ access to MMS within the VHA and provide a 10-year update to the survey findings of Karen and colleagues.11 Compared with their study, this survey offers a more granular description of practices and facilities as well as comparisons of VHA care with care purchased from outside sources. In outlining the state of MMS care within the VHA, this study highlights progress made and provides the updated data needed for continued efforts to optimize care and resource allocation for patients who require MMS within the VHA.
Although the number of VHA sites that provide MMS has increased over the past 10 years—from 11 sites in 9 states in 2007 to 19 sites in 13 states now—it is important to note that access to MMS care highly depends on geographic location.11 The VHA sites that provide MMS are clustered in major cities along the coasts. Four states (California, Florida, New York, and Texas) had > 1 MMS site, whereas most other states did not have any. In addition, only 1 MMS site served all of the northwest U.S. To ensure the anonymity of survey respondents, the authors did not further characterize the regional distribution of MMS sites.
Despite the increase in MMS sites, the number of MMS cases performed within the VHA seemed to have decreased. An estimated 8,310 cases were performed within the VHA in 2006,which decreased to 6,686 in 2015.11 Although these are estimates, the number of VHA cases likely decreased because of a rise in purchased care. Reviewing VHA electronic health records, Yoon and colleagues found that 19,681 MMS cases were performed either within the VHA or at non-VA medical care sites in 2012.1 Although the proportions of MMS cases performed within and outside the VHA were not reported, clearly many veterans had MMS performed through the VHA in recent years, and a high percentage of these cases were external referrals. More study is needed to further characterize MMS care within the VHA and MMS care purchased.
The 19 sites that provided MMS were evenly divided by volume: high (> 500 cases/y), medium (200-500 cases/y), and low (< 200 cases/y). Case volume correlated with the numbers of surgeons, nurses, and support staff at each site. Number of patient rooms dedicated to MMS at each site was not correlated with case volume; however, not ascertaining the number of days per week MMS was performed may have contributed to the lack of observed correlation.The majority of Mohs surgeons (25; 89.3%) within the VHA were affiliated with academic programs, which may partly explain the uneven geographic distribution of VHA sites that provide MMS (dermatology residency programs typically are in larger cities). The majority of Mohs surgeons were fellowship-trained through the ACMS or the ACGME. As the ACGME first began accrediting fellowship programs in 2003, younger surgeons were more likely to have completed this fellowship. According to respondents from sites that did not provide MMS, noncompetitive VHA salaries might be a barrier to Mohs surgeon recruitment. If a shift to providing more MMS care within the VHA were desired, an effective strategy could be to raise surgeon salaries. Higher salaries would bring in more Mohs surgeons and thereby yield higher MMS case volumes at VHA sites.
However, whether MMS is best provided for veterans within the VHA or at outside sites through referrals warrants further study. More than 60% of sites provided access to MMS through purchased care, either by fee-basis/non-VA medical care referrals or by the patient-elected Veterans Choice program. According to 84.2% of respondents at MMS sites and 66.7% of respondents at non-MMS sites, patients received care within a reasonable amount of time. In addition, respondents at MMS sites estimated longer patient travel distance for surgery. Respondents reported being concerned about coordination of care and follow-up for patients who received MMS outside the VHA. Other than referrals to outside sites for MMS, current triage practices include referral to other surgical specialties within the VHA, predominantly ear, nose, and throat and plastic surgery, for WLE. Given that access to on-site MMS varies significantly by geographic location, on-site MMS may be preferable in some locations, and external referrals in others. Based on this study's findings, on-site MMS seems superior to external referrals in all respects except patient travel distance. More research is needed to determine the most cost-effective triage practices. One option would be to have each VISN develop a skin cancer care center of excellence that would assist providers in appropriate triage and management.
Limitations
A decade has passed since Karen and colleagues conducted their study on MMS within the VHA.11 Data from this study suggest some progress has been made in improving veterans’ access to MMS. However, VHA sites that provide MMS are still predominantly located in large cities. In cases in which VHA providers refer patients to outside facilities, care coordination and follow-up are challenging. The present findings provide a basis for continuing VHA efforts to optimize resource allocation and improve longitudinal care for veterans who require MMS for skin cancer. Another area of interest is the comparative cost-effectiveness of MMS care provided within the VHA rather than at outside sites through purchased care. The answer may depend on geographic location, as MMS demand may be higher in some regions than that of others. For patients who receive MMS care outside the VHA, efforts should be made to improve communication and follow-up between VHA and external providers.
This study was limited in that it surveyed only those VHA sites with dermatology services or sections. It is possible, though unlikely, that MMS also was provided through nondermatology services. This study’s 70.3% response rate (52/74 dermatology chiefs) matched that of Karen and colleagues.11 Nevertheless, given that 30% of the surveyed chiefs did not respond and that analysis was performed separately for 2 small subgroups, (19 VHA sites that provided on-site MMS and 33 VHA sites that did not), the present findings may not be representative of the VHA as a whole.
Another limitation was that the survey captured respondent estimates of surgical caseloads and resources. Confirmation of these estimates would require a review of internal medical records and workforce analyses, which was beyond the scope of this study.
Conclusion
Although some progress has been made over the past 10 years, access to MMS within the VHA remains limited. About one-third of VHA sites provide on-site MMS; the other two-thirds refer patients with skin cancer to MMS sites outside the VHA. According to their dermatology chiefs, VHA sites that provide MMS have adequate resources and staffing and acceptable wait times for surgery; the challenge is in patients’ long travel distances. At sites that do not provide MMS, patients have access to MMS as well, and acceptable wait times and travel distances; the challenge is in follow-up, especially with activation of the Veterans Choice program. Studies should focus on standardizing veterans’ care and improving their access to MMS.
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1. Yoon J, Phibbs CS, Chow A, Pomerantz H, Weinstock MA. Costs of keratinocyte carcinoma (nonmelanoma skin cancer) and actinic keratosis treatment in the Veterans Health Administration. Dermatol Surg. 2016;42(9):1041-1047.
2. Giroir BP, Wilensky GR. Reforming the Veterans Health Administration—beyond palliation of symptoms. N Engl J Med. 2015;373(18):1693-1695.
3. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Basal Cell Skin Cancer 1.2018. https://www.nccn.org/professionals/physician_gls/pdf/nmsc.pdf. Updated September 18, 2017. Accessed January 31, 2018.
4. Chren MM, Sahay AP, Bertenthal DS, Sen S, Landefeld CS. Quality-of-life outcomes of treatments for cutaneous basal cell carcinoma and squamous cell carcinoma. J Invest Dermatol. 2007;127(6):1351-1357.
5. Cook J, Zitelli JA. Mohs micrographic surgery: a cost analysis. J Am Acad Dermatol. 1998;39(5, pt 1):698-703.
6. Kauvar AN, Arpey CJ, Hruza G, Olbricht SM, Bennett R, Mahmoud BH. Consensus for nonmelanoma skin cancer treatment, part ii: squamous cell carcinoma, including a cost analysis of treatment methods. Dermatol Surg. 2015;41(11):1214-1240.
7. Kauvar AN, Cronin T Jr, Roenigk R, Hruza G, Bennett R; American Society for Dermatologic Surgery. Consensus for nonmelanoma skin cancer treatment: basal cell carcinoma, including a cost analysis of treatment methods. Dermatol Surg. 2015;41(5):550-571.
8. Chen JT, Kempton SJ, Rao VK. The economics of skin cancer: an analysis of Medicare payment data. Plast Reconstr Surg Glob Open. 2016;4(9):e868.
9. Tierney EP, Hanke CW. Cost effectiveness of Mohs micrographic surgery: review of the literature. J Drugs Dermatol. 2009;8(10):914-922.
10. Ad Hoc Task Force, Connolly SM, Baker DR, Coldiron BM, et al. AAD/ACMS/ASDSA/ASMS 2012 appropriate use criteria for Mohs micrographic surgery: a report of the American Academy of Dermatology, American College of Mohs Surgery, American Society for Dermatologic Surgery Association, and the American Society for Mohs Surgery. J Am Acad Dermatol. 2012;67(4):531-550.
11. Karen JK, Hale EK, Nehal KS, Levine VJ. Use of Mohs surgery by the Veterans Affairs Health Care System. J Am Acad Dermatol. 2009;60(6):1069-1070.
12. U.S. Department of Veterans Affairs. Expanded access to non-VA care through the Veterans Choice program. Interim final rule. Fed Regist. 2015;80(230):74991-74996.
1. Yoon J, Phibbs CS, Chow A, Pomerantz H, Weinstock MA. Costs of keratinocyte carcinoma (nonmelanoma skin cancer) and actinic keratosis treatment in the Veterans Health Administration. Dermatol Surg. 2016;42(9):1041-1047.
2. Giroir BP, Wilensky GR. Reforming the Veterans Health Administration—beyond palliation of symptoms. N Engl J Med. 2015;373(18):1693-1695.
3. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Basal Cell Skin Cancer 1.2018. https://www.nccn.org/professionals/physician_gls/pdf/nmsc.pdf. Updated September 18, 2017. Accessed January 31, 2018.
4. Chren MM, Sahay AP, Bertenthal DS, Sen S, Landefeld CS. Quality-of-life outcomes of treatments for cutaneous basal cell carcinoma and squamous cell carcinoma. J Invest Dermatol. 2007;127(6):1351-1357.
5. Cook J, Zitelli JA. Mohs micrographic surgery: a cost analysis. J Am Acad Dermatol. 1998;39(5, pt 1):698-703.
6. Kauvar AN, Arpey CJ, Hruza G, Olbricht SM, Bennett R, Mahmoud BH. Consensus for nonmelanoma skin cancer treatment, part ii: squamous cell carcinoma, including a cost analysis of treatment methods. Dermatol Surg. 2015;41(11):1214-1240.
7. Kauvar AN, Cronin T Jr, Roenigk R, Hruza G, Bennett R; American Society for Dermatologic Surgery. Consensus for nonmelanoma skin cancer treatment: basal cell carcinoma, including a cost analysis of treatment methods. Dermatol Surg. 2015;41(5):550-571.
8. Chen JT, Kempton SJ, Rao VK. The economics of skin cancer: an analysis of Medicare payment data. Plast Reconstr Surg Glob Open. 2016;4(9):e868.
9. Tierney EP, Hanke CW. Cost effectiveness of Mohs micrographic surgery: review of the literature. J Drugs Dermatol. 2009;8(10):914-922.
10. Ad Hoc Task Force, Connolly SM, Baker DR, Coldiron BM, et al. AAD/ACMS/ASDSA/ASMS 2012 appropriate use criteria for Mohs micrographic surgery: a report of the American Academy of Dermatology, American College of Mohs Surgery, American Society for Dermatologic Surgery Association, and the American Society for Mohs Surgery. J Am Acad Dermatol. 2012;67(4):531-550.
11. Karen JK, Hale EK, Nehal KS, Levine VJ. Use of Mohs surgery by the Veterans Affairs Health Care System. J Am Acad Dermatol. 2009;60(6):1069-1070.
12. U.S. Department of Veterans Affairs. Expanded access to non-VA care through the Veterans Choice program. Interim final rule. Fed Regist. 2015;80(230):74991-74996.
Sore on nose
The FP suspected that it could be a skin cancer because any nonhealing lesion in sun-exposed areas could be skin cancer (especially basal cell carcinoma and squamous cell carcinoma).
He explained this to the patient and obtained written consent for a shave biopsy. He told the patient that the biopsy would likely leave an indentation in the involved area, but since treating the sore would likely require a second surgery, this indented area could be cut out and repaired with sutures. The patient indicated that he was more concerned about getting a proper diagnosis than he was about the appearance of the biopsy site.
The physician injected the area with 1% lidocaine and epinephrine for anesthesia and to prevent bleeding. (Remember, it is safe to use injectable epinephrine along with lidocaine when doing surgery on the nose. See “Biopsies for skin cancer detection: Dispelling the myths.”) The shave biopsy was performed using a Dermablade. (See the Watch & Learn video on “Shave biopsy.”) The pathology report revealed squamous cell carcinoma. The patient was referred for Mohs surgery to get the best cure and cosmetic result.
Photo courtesy of Jonathan Karnes, MD and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Karnes J, Usatine R. Squamous cell carcinoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1103-1111.
To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/
You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com
The FP suspected that it could be a skin cancer because any nonhealing lesion in sun-exposed areas could be skin cancer (especially basal cell carcinoma and squamous cell carcinoma).
He explained this to the patient and obtained written consent for a shave biopsy. He told the patient that the biopsy would likely leave an indentation in the involved area, but since treating the sore would likely require a second surgery, this indented area could be cut out and repaired with sutures. The patient indicated that he was more concerned about getting a proper diagnosis than he was about the appearance of the biopsy site.
The physician injected the area with 1% lidocaine and epinephrine for anesthesia and to prevent bleeding. (Remember, it is safe to use injectable epinephrine along with lidocaine when doing surgery on the nose. See “Biopsies for skin cancer detection: Dispelling the myths.”) The shave biopsy was performed using a Dermablade. (See the Watch & Learn video on “Shave biopsy.”) The pathology report revealed squamous cell carcinoma. The patient was referred for Mohs surgery to get the best cure and cosmetic result.
Photo courtesy of Jonathan Karnes, MD and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Karnes J, Usatine R. Squamous cell carcinoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1103-1111.
To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/
You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com
The FP suspected that it could be a skin cancer because any nonhealing lesion in sun-exposed areas could be skin cancer (especially basal cell carcinoma and squamous cell carcinoma).
He explained this to the patient and obtained written consent for a shave biopsy. He told the patient that the biopsy would likely leave an indentation in the involved area, but since treating the sore would likely require a second surgery, this indented area could be cut out and repaired with sutures. The patient indicated that he was more concerned about getting a proper diagnosis than he was about the appearance of the biopsy site.
The physician injected the area with 1% lidocaine and epinephrine for anesthesia and to prevent bleeding. (Remember, it is safe to use injectable epinephrine along with lidocaine when doing surgery on the nose. See “Biopsies for skin cancer detection: Dispelling the myths.”) The shave biopsy was performed using a Dermablade. (See the Watch & Learn video on “Shave biopsy.”) The pathology report revealed squamous cell carcinoma. The patient was referred for Mohs surgery to get the best cure and cosmetic result.
Photo courtesy of Jonathan Karnes, MD and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Karnes J, Usatine R. Squamous cell carcinoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1103-1111.
To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/
You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com
