Commentary

The prevalence of fibromyalgia in our clinical practices is about 2%-3%. But it may feel much higher, because some of these patients use a lot of staff and office time. Vacillations in our certainty about the diagnosis, inadequate time to differentiate new problems from the underlying one, failing to engage the patient in disease self-management, and inadequately exhausting the plethora of pharmacologic management options (however weak the data may be for each one) make care of patients with fibromyalgia challenging. Unfortunately, many of these patients are treated with chronic opioids.

So, maybe you have tried every pharmacologic option under the sun. But have you tried memantine?

Dr. Bárbara Olivan-Blázquez of the University of Zaragoza, Spain, and colleagues evaluated the efficacy of memantine for pain symptom control in fibromyalgia (Pain. 2014 Dec;155[12]:2517-25).

In this study, 63 patients with fibromyalgia were randomized to 20 mg/day of memantine or matching placebo for a total of 6 months, including an initial 1-month up-titration period. Follow-up occurred at 3 months and 6 months.

Compared with placebo, memantine decreased pain and depression at 3 months and 6 months. It also increased cognitive function and overall perceptions of function at 3 months and 6 months. More than 80% of patients completed the trial. Dizziness and headaches were the most commonly reported symptoms.

Why does it work? Memantine blocks glutamate, and glutamate may be a player in perpetuating the pain cycle for patients with fibromyalgia. Previously, memantine had been shown to be effective in other pain conditions such as complex regional pain syndrome and phantom limb pain. Memantine is well tolerated and is generically available. In my location, I was able to locate it for less than $1 per day of therapy.

So, before giving up hope or reaching for the opioid du jour, memantine may be worth a trial to decrease pain and improve function in our patients with fibromyalgia.

Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author and do not necessarily represent the views and opinions of the Mayo Clinic. The opinions expressed in this article should not be used to diagnose or treat any medical condition nor should they be used as a substitute for medical advice from a qualified, board-certified practicing clinician. Dr. Ebbert has no relevant financial disclosures about this article. Follow him on Twitter @jonebbert.

The prevalence of fibromyalgia in our clinical practices is about 2%-3%. But it may feel much higher, because some of these patients use a lot of staff and office time. Vacillations in our certainty about the diagnosis, inadequate time to differentiate new problems from the underlying one, failing to engage the patient in disease self-management, and inadequately exhausting the plethora of pharmacologic management options (however weak the data may be for each one) make care of patients with fibromyalgia challenging. Unfortunately, many of these patients are treated with chronic opioids.

So, maybe you have tried every pharmacologic option under the sun. But have you tried memantine?

Dr. Bárbara Olivan-Blázquez of the University of Zaragoza, Spain, and colleagues evaluated the efficacy of memantine for pain symptom control in fibromyalgia (Pain. 2014 Dec;155[12]:2517-25).

In this study, 63 patients with fibromyalgia were randomized to 20 mg/day of memantine or matching placebo for a total of 6 months, including an initial 1-month up-titration period. Follow-up occurred at 3 months and 6 months.

Compared with placebo, memantine decreased pain and depression at 3 months and 6 months. It also increased cognitive function and overall perceptions of function at 3 months and 6 months. More than 80% of patients completed the trial. Dizziness and headaches were the most commonly reported symptoms.

Why does it work? Memantine blocks glutamate, and glutamate may be a player in perpetuating the pain cycle for patients with fibromyalgia. Previously, memantine had been shown to be effective in other pain conditions such as complex regional pain syndrome and phantom limb pain. Memantine is well tolerated and is generically available. In my location, I was able to locate it for less than $1 per day of therapy.

So, before giving up hope or reaching for the opioid du jour, memantine may be worth a trial to decrease pain and improve function in our patients with fibromyalgia.

Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author and do not necessarily represent the views and opinions of the Mayo Clinic. The opinions expressed in this article should not be used to diagnose or treat any medical condition nor should they be used as a substitute for medical advice from a qualified, board-certified practicing clinician. Dr. Ebbert has no relevant financial disclosures about this article. Follow him on Twitter @jonebbert.

The prevalence of fibromyalgia in our clinical practices is about 2%-3%. But it may feel much higher, because some of these patients use a lot of staff and office time. Vacillations in our certainty about the diagnosis, inadequate time to differentiate new problems from the underlying one, failing to engage the patient in disease self-management, and inadequately exhausting the plethora of pharmacologic management options (however weak the data may be for each one) make care of patients with fibromyalgia challenging. Unfortunately, many of these patients are treated with chronic opioids.

So, maybe you have tried every pharmacologic option under the sun. But have you tried memantine?

Dr. Bárbara Olivan-Blázquez of the University of Zaragoza, Spain, and colleagues evaluated the efficacy of memantine for pain symptom control in fibromyalgia (Pain. 2014 Dec;155[12]:2517-25).

In this study, 63 patients with fibromyalgia were randomized to 20 mg/day of memantine or matching placebo for a total of 6 months, including an initial 1-month up-titration period. Follow-up occurred at 3 months and 6 months.

Compared with placebo, memantine decreased pain and depression at 3 months and 6 months. It also increased cognitive function and overall perceptions of function at 3 months and 6 months. More than 80% of patients completed the trial. Dizziness and headaches were the most commonly reported symptoms.

Why does it work? Memantine blocks glutamate, and glutamate may be a player in perpetuating the pain cycle for patients with fibromyalgia. Previously, memantine had been shown to be effective in other pain conditions such as complex regional pain syndrome and phantom limb pain. Memantine is well tolerated and is generically available. In my location, I was able to locate it for less than $1 per day of therapy.

So, before giving up hope or reaching for the opioid du jour, memantine may be worth a trial to decrease pain and improve function in our patients with fibromyalgia.

Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author and do not necessarily represent the views and opinions of the Mayo Clinic. The opinions expressed in this article should not be used to diagnose or treat any medical condition nor should they be used as a substitute for medical advice from a qualified, board-certified practicing clinician. Dr. Ebbert has no relevant financial disclosures about this article. Follow him on Twitter @jonebbert.

Vulvar intraepithelial neoplasia is a premalignant lesion of the vulva frequently encountered by gynecologic providers. There has been an increase in the incidence of VIN in younger women in recent decades thought be to be secondary to human papillomavirus infection, cigarette smoking, and sexual behavior (J Reprod Med. 2000 Aug;45[8]:613-5).

Data from the Surveillance Epidemiology and End Results (SEER) database were significant for a 411% increase in the incidence of in situ carcinoma and a 20% increase in invasive vulvar carcinoma from 1973 to 2000 (Obstet Gynecol. 2006 May;107[5]:1018-22). In addition, younger age groups are seeing an increase of in situ disease until age 49. Vulvar cancer however, continues to be a disease of older age.

Terminology

Previously, the term vulvar intraepithelial neoplasia followed the cervical intraepithelial neoplasia (CIN) designation in the 1960s. Conventions for grading these lesions have changed over time. Most recently, in 2004, the International Society for the Study of Vulvar Disease (ISSVD), composed of dermatologists, pathologists, and gynecologists, agreed to change the classification of squamous VIN from the previous VIN 1-3 classification system. The committee described VIN in two forms, “usual type” and “differentiated type” (J Reprod Med 2005;50:807-10).

In making this transition, it was recognized that VIN 1 is not in fact an oncogenic lesion and is now solely referred to as condyloma acuminatum. Grade 2 and 3 are now collectively referred to as VIN. These changes made by the ISSVD reflect the current literature on grading of VIN. In addition to VIN 1 not having any progression to malignancy, it is a diagnosis that is difficult to reproduce and may, at times, reflect reactive changes or other dermatosis. VIN 2 and 3 are not discriminated from each other in a reproducible manner and clinically have no reason for individual distinction (J Low Genit Tract Dis. 2006 Jul;10[3]:161-9).

VIN, usual type is the most common intraepithelial lesion and is historically referred to as classic VIN or Bowen’s disease. This type is associated with HPV infection and includes the formerly described warty type, basaloid type, and mixed type. The carcinogenic subtypes of HPV, 16, 18, 31, and 33 are the most common HPV subtypes responsible. It should be noted, however, that diagnosis is morphological and not based on HPV testing. Usual type is also traditionally thought to be more closely associated with risk factors such as smoking and immunocompromised states.

VIN, differentiated type is not associated with the HPV virus and is frequently found in older women. This lesion is often associated with other dermatologic conditions such as lichen sclerosis and lichen simplex chronicus. Diagnosis is also made by histology with abnormal cells being confined to the parabasal and basal portion of the rete pegs. This type also finds genetic alterations that are seen in invasive squamous cell carcinoma (Appl Immunohistochem Mol Morphol 2001;9:150-63). Differentiated type is thought to be a precursor for HPV-negative keratinizing squamous cell carcinoma of the vulva (Am J Surg Pathol. 2000 Mar;24[3]:429-41).

As awareness of this distinct form of VIN increases and more is learned about the precursors of HPV-negative squamous cell carcinoma, physicians are encouraged to closely follow up hyperplastic lesions and lichen sclerosis with biopsies and excision. The diagnosis of differentiated VIN is rarely made at present; however, this distinction by the ISSVD may improve the ability of clinicians and pathologists to recognize this HPV-negative precursor before squamous cell carcinoma is present.

The Lower Anogenital Squamous Terminology project of the College of American Pathology and the American Society for Colposcopy and Cervical Pathology advocates for more consistent terminology across lower anogenital tract lesions. This terminology applies only to HPV-related lesions (usual type) and considers the VIN 1 or condyloma accuminatum to be a low-grade lesion (LSIL), and VIN 2-3 or usual type to be high-grade lesions (HSIL) (Int J Gynecol Pathol. 2013 Jan;32[1]:76-115).

Many clinicians and pathologists have not adopted this most recent terminology; however, there is evidence that the ISSVD classification is the most clinically relevant.

Diagnosis

The majority of patients with any VIN will present with complaints of vulvar pruritus. However, women can also present with pain, burning, or dysuria, or can have an asymptomatic lesion found on pelvic exam. There are no recommended screening strategies to diagnose early VIN. Cytologic testing is complicated by the keratinization of the vulva, making this an unreliable diagnostic assessment.

On physical exam, VIN can have a heterogeneous presentation including papules, plaques, color variations, or ulcer. Differentiated type is thought to have a more defined appearance that frequently develops in the setting of other vulvar dermatosis. These are distinct, solitary lesions that are commonly raised, can have an overlying scale, and have ill-defined borders. A distinct lesion with ulceration or erosion is concerning for invasion.

Diagnosis is ultimately made by biopsy. Physicians should have a low threshold to biopsy any suspicious lesions or those unresponsive to therapy. Colposcopy is a frequent adjunct to the physical exam. Acetic acid 3%-5% soaked gauze is allowed to rest on the vulva for several minutes prior to observation with a colposcope or hand-held magnifying glass. Colposcopic findings are usually those of focal “white” epithelium. Vascular changes seen on the cervix (punctuation and mosaicism) are rarely seen on the vulva.

The entire anogenital region shares the same susceptibility to the HPV virus, thus squamous intraepithelial lesions are frequently multifocal. Physicians should have a heightened awareness of other lesions, such as cervical, vaginal, or anal, when managing a patient with VIN (Gynecol Oncol. 1995 Feb;56[2]:276-9). Appropriate cervical screening should be strictly adhered to and a thorough exam done at the time of vulvar colposcopy or exam.

Treatment

The goals of treatment include preventing carcinoma and improving symptoms while maintaining function and preserving anatomy. Treatment options for both types of VIN include excision, ablation, or medical therapy pending an evaluation of concurrent risk factors.

Premalignant disease was traditionally treated surgically. While surgical excision is still the mainstay of therapy, less aggressive techniques and medical therapy are more readily utilized. The goal of surgical excision for VIN is both diagnostic and therapeutic. When an excision for high-grade dysplasia is done (formerly VIN 3), detection of occult carcinoma was found in up to 3.2% in one large review (Gynecol Oncol. 2005;97:645-51).

Using a wide local excision to completely remove lesions with a pathologically clear margin reduces a patient’s risk of recurrence for disease compared to those excisions with positive margins (Obstet Gynecol. 1998;92:962-6). It is therefore critical that physicians carefully counsel patients who desire conservative therapy for VIN.

With any treatment, however, patients and physicians should be aware of the risk of recurrence; for vulvectomy, partial vulvectomy, local excision, and laser ablation, recurrences were seen at rates of 19%, 18%, 22%, and 23%, respectively, in a review of 3,322 patients (Gynecol Oncol. 2005;97:645-51).

CO₂ laser ablation has been used for single lesions as well as multifocal or confluent disease. Many physicians advocate for its use in patients with multifocal lesions as well as those with disease around the clitoris or anus, where excisional therapy is less desirable as laser therapy results in less scarring.

A 2015 Cochrane Database Review of medical therapy for high-grade dysplasia (usual-type VIN, VIN 2/3, or high-grade VIN) found that topical imiquimod can be used as a safe and effective option for high-grade VIN. Physicians should, however, be aware of unfavorable side effects that may require dose reductions. Cidofovir may be an alternative to imiquimod pending more evidence on long-term response and progression (Cochrane Database Syst Rev. 2015 Aug 18;8:CD007924). Topical 5-fluorouracil has fallen out of favor for VIN given its significant chemical desquamation, however response rates are thought to be favorable if tolerated.

As the use of VIN terminology solidifies and information emerges on medical therapy to treat VIN, it is critical that physicians remain current when counseling and providing treatment recommendations for vulvar intraepithelial neoplasia.

Dr. Gehrig is professor and director of gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Clarke-Pearson is the chair and the Robert A. Ross Distinguished Professor of Obstetrics and Gynecology and professor in the division of gynecologic oncology at the university. Dr. Sullivan is a fellow in the division of gynecologic oncology at the university. They reported having no relevant financial disclosures. Email them at [email protected].

Vulvar intraepithelial neoplasia is a premalignant lesion of the vulva frequently encountered by gynecologic providers. There has been an increase in the incidence of VIN in younger women in recent decades thought be to be secondary to human papillomavirus infection, cigarette smoking, and sexual behavior (J Reprod Med. 2000 Aug;45[8]:613-5).

Data from the Surveillance Epidemiology and End Results (SEER) database were significant for a 411% increase in the incidence of in situ carcinoma and a 20% increase in invasive vulvar carcinoma from 1973 to 2000 (Obstet Gynecol. 2006 May;107[5]:1018-22). In addition, younger age groups are seeing an increase of in situ disease until age 49. Vulvar cancer however, continues to be a disease of older age.

Terminology

Previously, the term vulvar intraepithelial neoplasia followed the cervical intraepithelial neoplasia (CIN) designation in the 1960s. Conventions for grading these lesions have changed over time. Most recently, in 2004, the International Society for the Study of Vulvar Disease (ISSVD), composed of dermatologists, pathologists, and gynecologists, agreed to change the classification of squamous VIN from the previous VIN 1-3 classification system. The committee described VIN in two forms, “usual type” and “differentiated type” (J Reprod Med 2005;50:807-10).

In making this transition, it was recognized that VIN 1 is not in fact an oncogenic lesion and is now solely referred to as condyloma acuminatum. Grade 2 and 3 are now collectively referred to as VIN. These changes made by the ISSVD reflect the current literature on grading of VIN. In addition to VIN 1 not having any progression to malignancy, it is a diagnosis that is difficult to reproduce and may, at times, reflect reactive changes or other dermatosis. VIN 2 and 3 are not discriminated from each other in a reproducible manner and clinically have no reason for individual distinction (J Low Genit Tract Dis. 2006 Jul;10[3]:161-9).

VIN, usual type is the most common intraepithelial lesion and is historically referred to as classic VIN or Bowen’s disease. This type is associated with HPV infection and includes the formerly described warty type, basaloid type, and mixed type. The carcinogenic subtypes of HPV, 16, 18, 31, and 33 are the most common HPV subtypes responsible. It should be noted, however, that diagnosis is morphological and not based on HPV testing. Usual type is also traditionally thought to be more closely associated with risk factors such as smoking and immunocompromised states.

VIN, differentiated type is not associated with the HPV virus and is frequently found in older women. This lesion is often associated with other dermatologic conditions such as lichen sclerosis and lichen simplex chronicus. Diagnosis is also made by histology with abnormal cells being confined to the parabasal and basal portion of the rete pegs. This type also finds genetic alterations that are seen in invasive squamous cell carcinoma (Appl Immunohistochem Mol Morphol 2001;9:150-63). Differentiated type is thought to be a precursor for HPV-negative keratinizing squamous cell carcinoma of the vulva (Am J Surg Pathol. 2000 Mar;24[3]:429-41).

As awareness of this distinct form of VIN increases and more is learned about the precursors of HPV-negative squamous cell carcinoma, physicians are encouraged to closely follow up hyperplastic lesions and lichen sclerosis with biopsies and excision. The diagnosis of differentiated VIN is rarely made at present; however, this distinction by the ISSVD may improve the ability of clinicians and pathologists to recognize this HPV-negative precursor before squamous cell carcinoma is present.

The Lower Anogenital Squamous Terminology project of the College of American Pathology and the American Society for Colposcopy and Cervical Pathology advocates for more consistent terminology across lower anogenital tract lesions. This terminology applies only to HPV-related lesions (usual type) and considers the VIN 1 or condyloma accuminatum to be a low-grade lesion (LSIL), and VIN 2-3 or usual type to be high-grade lesions (HSIL) (Int J Gynecol Pathol. 2013 Jan;32[1]:76-115).

Many clinicians and pathologists have not adopted this most recent terminology; however, there is evidence that the ISSVD classification is the most clinically relevant.

Diagnosis

The majority of patients with any VIN will present with complaints of vulvar pruritus. However, women can also present with pain, burning, or dysuria, or can have an asymptomatic lesion found on pelvic exam. There are no recommended screening strategies to diagnose early VIN. Cytologic testing is complicated by the keratinization of the vulva, making this an unreliable diagnostic assessment.

On physical exam, VIN can have a heterogeneous presentation including papules, plaques, color variations, or ulcer. Differentiated type is thought to have a more defined appearance that frequently develops in the setting of other vulvar dermatosis. These are distinct, solitary lesions that are commonly raised, can have an overlying scale, and have ill-defined borders. A distinct lesion with ulceration or erosion is concerning for invasion.

Diagnosis is ultimately made by biopsy. Physicians should have a low threshold to biopsy any suspicious lesions or those unresponsive to therapy. Colposcopy is a frequent adjunct to the physical exam. Acetic acid 3%-5% soaked gauze is allowed to rest on the vulva for several minutes prior to observation with a colposcope or hand-held magnifying glass. Colposcopic findings are usually those of focal “white” epithelium. Vascular changes seen on the cervix (punctuation and mosaicism) are rarely seen on the vulva.

The entire anogenital region shares the same susceptibility to the HPV virus, thus squamous intraepithelial lesions are frequently multifocal. Physicians should have a heightened awareness of other lesions, such as cervical, vaginal, or anal, when managing a patient with VIN (Gynecol Oncol. 1995 Feb;56[2]:276-9). Appropriate cervical screening should be strictly adhered to and a thorough exam done at the time of vulvar colposcopy or exam.

Treatment

The goals of treatment include preventing carcinoma and improving symptoms while maintaining function and preserving anatomy. Treatment options for both types of VIN include excision, ablation, or medical therapy pending an evaluation of concurrent risk factors.

Premalignant disease was traditionally treated surgically. While surgical excision is still the mainstay of therapy, less aggressive techniques and medical therapy are more readily utilized. The goal of surgical excision for VIN is both diagnostic and therapeutic. When an excision for high-grade dysplasia is done (formerly VIN 3), detection of occult carcinoma was found in up to 3.2% in one large review (Gynecol Oncol. 2005;97:645-51).

Using a wide local excision to completely remove lesions with a pathologically clear margin reduces a patient’s risk of recurrence for disease compared to those excisions with positive margins (Obstet Gynecol. 1998;92:962-6). It is therefore critical that physicians carefully counsel patients who desire conservative therapy for VIN.

With any treatment, however, patients and physicians should be aware of the risk of recurrence; for vulvectomy, partial vulvectomy, local excision, and laser ablation, recurrences were seen at rates of 19%, 18%, 22%, and 23%, respectively, in a review of 3,322 patients (Gynecol Oncol. 2005;97:645-51).

CO₂ laser ablation has been used for single lesions as well as multifocal or confluent disease. Many physicians advocate for its use in patients with multifocal lesions as well as those with disease around the clitoris or anus, where excisional therapy is less desirable as laser therapy results in less scarring.

A 2015 Cochrane Database Review of medical therapy for high-grade dysplasia (usual-type VIN, VIN 2/3, or high-grade VIN) found that topical imiquimod can be used as a safe and effective option for high-grade VIN. Physicians should, however, be aware of unfavorable side effects that may require dose reductions. Cidofovir may be an alternative to imiquimod pending more evidence on long-term response and progression (Cochrane Database Syst Rev. 2015 Aug 18;8:CD007924). Topical 5-fluorouracil has fallen out of favor for VIN given its significant chemical desquamation, however response rates are thought to be favorable if tolerated.

As the use of VIN terminology solidifies and information emerges on medical therapy to treat VIN, it is critical that physicians remain current when counseling and providing treatment recommendations for vulvar intraepithelial neoplasia.

Dr. Gehrig is professor and director of gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Clarke-Pearson is the chair and the Robert A. Ross Distinguished Professor of Obstetrics and Gynecology and professor in the division of gynecologic oncology at the university. Dr. Sullivan is a fellow in the division of gynecologic oncology at the university. They reported having no relevant financial disclosures. Email them at [email protected].

Vulvar intraepithelial neoplasia is a premalignant lesion of the vulva frequently encountered by gynecologic providers. There has been an increase in the incidence of VIN in younger women in recent decades thought be to be secondary to human papillomavirus infection, cigarette smoking, and sexual behavior (J Reprod Med. 2000 Aug;45[8]:613-5).

Data from the Surveillance Epidemiology and End Results (SEER) database were significant for a 411% increase in the incidence of in situ carcinoma and a 20% increase in invasive vulvar carcinoma from 1973 to 2000 (Obstet Gynecol. 2006 May;107[5]:1018-22). In addition, younger age groups are seeing an increase of in situ disease until age 49. Vulvar cancer however, continues to be a disease of older age.

Terminology

Previously, the term vulvar intraepithelial neoplasia followed the cervical intraepithelial neoplasia (CIN) designation in the 1960s. Conventions for grading these lesions have changed over time. Most recently, in 2004, the International Society for the Study of Vulvar Disease (ISSVD), composed of dermatologists, pathologists, and gynecologists, agreed to change the classification of squamous VIN from the previous VIN 1-3 classification system. The committee described VIN in two forms, “usual type” and “differentiated type” (J Reprod Med 2005;50:807-10).

In making this transition, it was recognized that VIN 1 is not in fact an oncogenic lesion and is now solely referred to as condyloma acuminatum. Grade 2 and 3 are now collectively referred to as VIN. These changes made by the ISSVD reflect the current literature on grading of VIN. In addition to VIN 1 not having any progression to malignancy, it is a diagnosis that is difficult to reproduce and may, at times, reflect reactive changes or other dermatosis. VIN 2 and 3 are not discriminated from each other in a reproducible manner and clinically have no reason for individual distinction (J Low Genit Tract Dis. 2006 Jul;10[3]:161-9).

VIN, usual type is the most common intraepithelial lesion and is historically referred to as classic VIN or Bowen’s disease. This type is associated with HPV infection and includes the formerly described warty type, basaloid type, and mixed type. The carcinogenic subtypes of HPV, 16, 18, 31, and 33 are the most common HPV subtypes responsible. It should be noted, however, that diagnosis is morphological and not based on HPV testing. Usual type is also traditionally thought to be more closely associated with risk factors such as smoking and immunocompromised states.

VIN, differentiated type is not associated with the HPV virus and is frequently found in older women. This lesion is often associated with other dermatologic conditions such as lichen sclerosis and lichen simplex chronicus. Diagnosis is also made by histology with abnormal cells being confined to the parabasal and basal portion of the rete pegs. This type also finds genetic alterations that are seen in invasive squamous cell carcinoma (Appl Immunohistochem Mol Morphol 2001;9:150-63). Differentiated type is thought to be a precursor for HPV-negative keratinizing squamous cell carcinoma of the vulva (Am J Surg Pathol. 2000 Mar;24[3]:429-41).

As awareness of this distinct form of VIN increases and more is learned about the precursors of HPV-negative squamous cell carcinoma, physicians are encouraged to closely follow up hyperplastic lesions and lichen sclerosis with biopsies and excision. The diagnosis of differentiated VIN is rarely made at present; however, this distinction by the ISSVD may improve the ability of clinicians and pathologists to recognize this HPV-negative precursor before squamous cell carcinoma is present.

The Lower Anogenital Squamous Terminology project of the College of American Pathology and the American Society for Colposcopy and Cervical Pathology advocates for more consistent terminology across lower anogenital tract lesions. This terminology applies only to HPV-related lesions (usual type) and considers the VIN 1 or condyloma accuminatum to be a low-grade lesion (LSIL), and VIN 2-3 or usual type to be high-grade lesions (HSIL) (Int J Gynecol Pathol. 2013 Jan;32[1]:76-115).

Many clinicians and pathologists have not adopted this most recent terminology; however, there is evidence that the ISSVD classification is the most clinically relevant.

Diagnosis

The majority of patients with any VIN will present with complaints of vulvar pruritus. However, women can also present with pain, burning, or dysuria, or can have an asymptomatic lesion found on pelvic exam. There are no recommended screening strategies to diagnose early VIN. Cytologic testing is complicated by the keratinization of the vulva, making this an unreliable diagnostic assessment.

On physical exam, VIN can have a heterogeneous presentation including papules, plaques, color variations, or ulcer. Differentiated type is thought to have a more defined appearance that frequently develops in the setting of other vulvar dermatosis. These are distinct, solitary lesions that are commonly raised, can have an overlying scale, and have ill-defined borders. A distinct lesion with ulceration or erosion is concerning for invasion.

Diagnosis is ultimately made by biopsy. Physicians should have a low threshold to biopsy any suspicious lesions or those unresponsive to therapy. Colposcopy is a frequent adjunct to the physical exam. Acetic acid 3%-5% soaked gauze is allowed to rest on the vulva for several minutes prior to observation with a colposcope or hand-held magnifying glass. Colposcopic findings are usually those of focal “white” epithelium. Vascular changes seen on the cervix (punctuation and mosaicism) are rarely seen on the vulva.

The entire anogenital region shares the same susceptibility to the HPV virus, thus squamous intraepithelial lesions are frequently multifocal. Physicians should have a heightened awareness of other lesions, such as cervical, vaginal, or anal, when managing a patient with VIN (Gynecol Oncol. 1995 Feb;56[2]:276-9). Appropriate cervical screening should be strictly adhered to and a thorough exam done at the time of vulvar colposcopy or exam.

Treatment

The goals of treatment include preventing carcinoma and improving symptoms while maintaining function and preserving anatomy. Treatment options for both types of VIN include excision, ablation, or medical therapy pending an evaluation of concurrent risk factors.

Premalignant disease was traditionally treated surgically. While surgical excision is still the mainstay of therapy, less aggressive techniques and medical therapy are more readily utilized. The goal of surgical excision for VIN is both diagnostic and therapeutic. When an excision for high-grade dysplasia is done (formerly VIN 3), detection of occult carcinoma was found in up to 3.2% in one large review (Gynecol Oncol. 2005;97:645-51).

Using a wide local excision to completely remove lesions with a pathologically clear margin reduces a patient’s risk of recurrence for disease compared to those excisions with positive margins (Obstet Gynecol. 1998;92:962-6). It is therefore critical that physicians carefully counsel patients who desire conservative therapy for VIN.

With any treatment, however, patients and physicians should be aware of the risk of recurrence; for vulvectomy, partial vulvectomy, local excision, and laser ablation, recurrences were seen at rates of 19%, 18%, 22%, and 23%, respectively, in a review of 3,322 patients (Gynecol Oncol. 2005;97:645-51).

CO₂ laser ablation has been used for single lesions as well as multifocal or confluent disease. Many physicians advocate for its use in patients with multifocal lesions as well as those with disease around the clitoris or anus, where excisional therapy is less desirable as laser therapy results in less scarring.

A 2015 Cochrane Database Review of medical therapy for high-grade dysplasia (usual-type VIN, VIN 2/3, or high-grade VIN) found that topical imiquimod can be used as a safe and effective option for high-grade VIN. Physicians should, however, be aware of unfavorable side effects that may require dose reductions. Cidofovir may be an alternative to imiquimod pending more evidence on long-term response and progression (Cochrane Database Syst Rev. 2015 Aug 18;8:CD007924). Topical 5-fluorouracil has fallen out of favor for VIN given its significant chemical desquamation, however response rates are thought to be favorable if tolerated.

As the use of VIN terminology solidifies and information emerges on medical therapy to treat VIN, it is critical that physicians remain current when counseling and providing treatment recommendations for vulvar intraepithelial neoplasia.

Dr. Gehrig is professor and director of gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Clarke-Pearson is the chair and the Robert A. Ross Distinguished Professor of Obstetrics and Gynecology and professor in the division of gynecologic oncology at the university. Dr. Sullivan is a fellow in the division of gynecologic oncology at the university. They reported having no relevant financial disclosures. Email them at [email protected].

Registered letters are a pain in the butt.

In the grand scheme of things, they’re a minor nuisance, albeit necessary. Documentation is everything is this job.

So here and there, I stop by the post office on the way home. It’s almost $7 a letter now, so maybe $28 a month, $336 a year. Not a huge sum.

But it’s annoying. It’s money that could be used for other expenses, and 80% of the time, the reason I have to do it is someone isn’t returning a call.

I suspect the scenario is similar in your practice. Patients are due for a follow-up MRI, MR angiography, labs, or whatever. So your staff calls them a few times. If they don’t return the call, you mail them letters. If they don’t respond, you send them registered letters. That way, even if they never respond, you can document that someone at that address got the letter.

Patients have several chances to answer the phone or call my office to schedule or refuse the test before I resort to the letter. But, for whatever reasons, sometimes they ignore them, leaving me with a trip to the post office and $7 down.

About one-third of the time we still never hear back, which is fine if that’s what they want. As long as I get the signed card, I don’t mind. Another third of the time they call to schedule, often wondering why I had to resort to a registered letter. “I got your call and other letter, so why did you send that?” And the others? They call us, usually to say they don’t want the test, or just angry that we sent them a registered letter, or (my favorite) to accuse us of harassing them. Because, you know, I enjoy making the extra trip and cost just to do that.

Unfortunately, the consequences of not doing this are (potentially) worse. In most cases, nothing would happen. But, sooner or later you risk having a medical disaster possibly occur because of whatever you were following. And then, correctly or not, they may blame you and call a lawyer. While it’s not guaranteed protection, it’s helpful to be able to prove, with a signed card, that they got your letter and chose to ignore it.

Is that worth the $7 and extra stop? Absolutely. But still, I wish people would be kind enough to just answer the phone or return a call. If they don’t want to do the study, I’m not offended. I just don’t like wasting time and money because someone won’t pick up a phone.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Registered letters are a pain in the butt.

In the grand scheme of things, they’re a minor nuisance, albeit necessary. Documentation is everything is this job.

So here and there, I stop by the post office on the way home. It’s almost $7 a letter now, so maybe $28 a month, $336 a year. Not a huge sum.

But it’s annoying. It’s money that could be used for other expenses, and 80% of the time, the reason I have to do it is someone isn’t returning a call.

I suspect the scenario is similar in your practice. Patients are due for a follow-up MRI, MR angiography, labs, or whatever. So your staff calls them a few times. If they don’t return the call, you mail them letters. If they don’t respond, you send them registered letters. That way, even if they never respond, you can document that someone at that address got the letter.

Patients have several chances to answer the phone or call my office to schedule or refuse the test before I resort to the letter. But, for whatever reasons, sometimes they ignore them, leaving me with a trip to the post office and $7 down.

About one-third of the time we still never hear back, which is fine if that’s what they want. As long as I get the signed card, I don’t mind. Another third of the time they call to schedule, often wondering why I had to resort to a registered letter. “I got your call and other letter, so why did you send that?” And the others? They call us, usually to say they don’t want the test, or just angry that we sent them a registered letter, or (my favorite) to accuse us of harassing them. Because, you know, I enjoy making the extra trip and cost just to do that.

Unfortunately, the consequences of not doing this are (potentially) worse. In most cases, nothing would happen. But, sooner or later you risk having a medical disaster possibly occur because of whatever you were following. And then, correctly or not, they may blame you and call a lawyer. While it’s not guaranteed protection, it’s helpful to be able to prove, with a signed card, that they got your letter and chose to ignore it.

Is that worth the $7 and extra stop? Absolutely. But still, I wish people would be kind enough to just answer the phone or return a call. If they don’t want to do the study, I’m not offended. I just don’t like wasting time and money because someone won’t pick up a phone.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Registered letters are a pain in the butt.

In the grand scheme of things, they’re a minor nuisance, albeit necessary. Documentation is everything is this job.

So here and there, I stop by the post office on the way home. It’s almost $7 a letter now, so maybe $28 a month, $336 a year. Not a huge sum.

But it’s annoying. It’s money that could be used for other expenses, and 80% of the time, the reason I have to do it is someone isn’t returning a call.

I suspect the scenario is similar in your practice. Patients are due for a follow-up MRI, MR angiography, labs, or whatever. So your staff calls them a few times. If they don’t return the call, you mail them letters. If they don’t respond, you send them registered letters. That way, even if they never respond, you can document that someone at that address got the letter.

Patients have several chances to answer the phone or call my office to schedule or refuse the test before I resort to the letter. But, for whatever reasons, sometimes they ignore them, leaving me with a trip to the post office and $7 down.

About one-third of the time we still never hear back, which is fine if that’s what they want. As long as I get the signed card, I don’t mind. Another third of the time they call to schedule, often wondering why I had to resort to a registered letter. “I got your call and other letter, so why did you send that?” And the others? They call us, usually to say they don’t want the test, or just angry that we sent them a registered letter, or (my favorite) to accuse us of harassing them. Because, you know, I enjoy making the extra trip and cost just to do that.

Unfortunately, the consequences of not doing this are (potentially) worse. In most cases, nothing would happen. But, sooner or later you risk having a medical disaster possibly occur because of whatever you were following. And then, correctly or not, they may blame you and call a lawyer. While it’s not guaranteed protection, it’s helpful to be able to prove, with a signed card, that they got your letter and chose to ignore it.

Is that worth the $7 and extra stop? Absolutely. But still, I wish people would be kind enough to just answer the phone or return a call. If they don’t want to do the study, I’m not offended. I just don’t like wasting time and money because someone won’t pick up a phone.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

“Have a nice time!”

I looked around, trying to tell where the piping, childish voice was coming from. I’d just swiped the barcode of my pass to the local lake I swim in every summer. There it was – the voice of one of the high school kids who works at the lake. She wore a wan smile.

I’ve been swimming at this lake for 35 years. No kid ever said a word to me before. “Have a good swim!” said a young man standing at the desk where, “All Children Under 12 Must Check In!”

Goodness me, I thought. The management consultants have made it to the lake.

You know who I mean. The ones who see to it that front-desk personnel always flash a bright smile and recite the corporate script. At the hardware store, the fast-food chain, the airline counter. Even the people in the auto dealer’s service department smile and murmur sweet nothings. They used to glare and growl, and make you feel like an idiot. “Whatsamattter, Bud? Dontcha know anything about cars?” Now it’s all politeness and smiles and “How may we help you, kind sir?”

And of course there’s the pharmacy. When I fill my prescription, the tech flashes a bright grin of welcome. Either that, or she has tetanus.

“Welcome to DrugTown!” she says. “May I have your name?”

I tell her. She retrieves the prescription. “Verify your address?” I do.

“Do you have a DrugTown Rewards Card?” she asks. I enter in my cellphone number, swipe my card, turn to leave.

“Be sound!” she says, still grinning. The DrugTown motto is: “Where Safe Meets Sound!”

It is easy to mock this sort of thing as formulaic and false. Insincere or not, smiling makes a difference. Some say you can actually get happier by making yourself smile. Whether that’s true or not, watching other people smile and make eye contact makes you feel good. Seeing them scowl and look away does the reverse.

This is true in doctors’ offices too. I learned this recently by being a patient.

I approached the front desk at my first visit. The lone receptionist was looking at some papers. I tried to get her attention. “Hello,” I said, “My name is ... ”

Still looking down, she shoved a clipboard across the counter. “Sign in,” she said. “And fill this out.” She handed me a sheaf of forms. “Leave it here when you’re done.” She was still looking away.

I sat in one of the waiting room chairs to work on the forms. I felt bad. As I watched the clerk ignore a succession of other patients, I asked myself why I felt so bad. First of all, it wasn’t personal; she was churlish to everyone. Second, what did this have to do with my visit? I was there to see the doctor, not his receptionist. Weren’t his skill and expertise what mattered?

True enough, but I still felt lousy. At later visits I took on the personal challenge of trying to force the clerk to make eye contact. I failed. In truth, her behavior colored my impression of the medical experience – mixed anyway – more than the medical outcome.

Sometimes I force myself to look at my own online reviews. The bad ones often focus on the alleged rudeness of my staff. It can be hard to tell from cranky patients whether their complaints are justified. But sometimes they are.

Management consultants know this. They teach employers that the customer experience has to do with more than the quality of the good or service provided. Even if the quarter-pounder is delicious, it may not taste that way if the burger-flipper is having a bad day and doesn’t know how to hide it.

So my office manager now trains our front-desk staff to be insistently cheery. This can be hard when patients are stacked three-deep, each with a form to scan, a credit card to swipe, a follow-up to book. But smile we have them do.

We don’t, however, have them recite a script when smiling. (“Make the scene! Wear sunscreen!”) We’re not up to that chapter in the customer-service handbook.

Who do you think we are? The town lake?

Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. Write to him at [email protected].

“Have a nice time!”

I looked around, trying to tell where the piping, childish voice was coming from. I’d just swiped the barcode of my pass to the local lake I swim in every summer. There it was – the voice of one of the high school kids who works at the lake. She wore a wan smile.

I’ve been swimming at this lake for 35 years. No kid ever said a word to me before. “Have a good swim!” said a young man standing at the desk where, “All Children Under 12 Must Check In!”

Goodness me, I thought. The management consultants have made it to the lake.

You know who I mean. The ones who see to it that front-desk personnel always flash a bright smile and recite the corporate script. At the hardware store, the fast-food chain, the airline counter. Even the people in the auto dealer’s service department smile and murmur sweet nothings. They used to glare and growl, and make you feel like an idiot. “Whatsamattter, Bud? Dontcha know anything about cars?” Now it’s all politeness and smiles and “How may we help you, kind sir?”

And of course there’s the pharmacy. When I fill my prescription, the tech flashes a bright grin of welcome. Either that, or she has tetanus.

“Welcome to DrugTown!” she says. “May I have your name?”

I tell her. She retrieves the prescription. “Verify your address?” I do.

“Do you have a DrugTown Rewards Card?” she asks. I enter in my cellphone number, swipe my card, turn to leave.

“Be sound!” she says, still grinning. The DrugTown motto is: “Where Safe Meets Sound!”

It is easy to mock this sort of thing as formulaic and false. Insincere or not, smiling makes a difference. Some say you can actually get happier by making yourself smile. Whether that’s true or not, watching other people smile and make eye contact makes you feel good. Seeing them scowl and look away does the reverse.

This is true in doctors’ offices too. I learned this recently by being a patient.

I approached the front desk at my first visit. The lone receptionist was looking at some papers. I tried to get her attention. “Hello,” I said, “My name is ... ”

Still looking down, she shoved a clipboard across the counter. “Sign in,” she said. “And fill this out.” She handed me a sheaf of forms. “Leave it here when you’re done.” She was still looking away.

I sat in one of the waiting room chairs to work on the forms. I felt bad. As I watched the clerk ignore a succession of other patients, I asked myself why I felt so bad. First of all, it wasn’t personal; she was churlish to everyone. Second, what did this have to do with my visit? I was there to see the doctor, not his receptionist. Weren’t his skill and expertise what mattered?

True enough, but I still felt lousy. At later visits I took on the personal challenge of trying to force the clerk to make eye contact. I failed. In truth, her behavior colored my impression of the medical experience – mixed anyway – more than the medical outcome.

Sometimes I force myself to look at my own online reviews. The bad ones often focus on the alleged rudeness of my staff. It can be hard to tell from cranky patients whether their complaints are justified. But sometimes they are.

Management consultants know this. They teach employers that the customer experience has to do with more than the quality of the good or service provided. Even if the quarter-pounder is delicious, it may not taste that way if the burger-flipper is having a bad day and doesn’t know how to hide it.

So my office manager now trains our front-desk staff to be insistently cheery. This can be hard when patients are stacked three-deep, each with a form to scan, a credit card to swipe, a follow-up to book. But smile we have them do.

We don’t, however, have them recite a script when smiling. (“Make the scene! Wear sunscreen!”) We’re not up to that chapter in the customer-service handbook.

Who do you think we are? The town lake?

Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. Write to him at [email protected].

“Have a nice time!”

I looked around, trying to tell where the piping, childish voice was coming from. I’d just swiped the barcode of my pass to the local lake I swim in every summer. There it was – the voice of one of the high school kids who works at the lake. She wore a wan smile.

I’ve been swimming at this lake for 35 years. No kid ever said a word to me before. “Have a good swim!” said a young man standing at the desk where, “All Children Under 12 Must Check In!”

Goodness me, I thought. The management consultants have made it to the lake.

You know who I mean. The ones who see to it that front-desk personnel always flash a bright smile and recite the corporate script. At the hardware store, the fast-food chain, the airline counter. Even the people in the auto dealer’s service department smile and murmur sweet nothings. They used to glare and growl, and make you feel like an idiot. “Whatsamattter, Bud? Dontcha know anything about cars?” Now it’s all politeness and smiles and “How may we help you, kind sir?”

And of course there’s the pharmacy. When I fill my prescription, the tech flashes a bright grin of welcome. Either that, or she has tetanus.

“Welcome to DrugTown!” she says. “May I have your name?”

I tell her. She retrieves the prescription. “Verify your address?” I do.

“Do you have a DrugTown Rewards Card?” she asks. I enter in my cellphone number, swipe my card, turn to leave.

“Be sound!” she says, still grinning. The DrugTown motto is: “Where Safe Meets Sound!”

It is easy to mock this sort of thing as formulaic and false. Insincere or not, smiling makes a difference. Some say you can actually get happier by making yourself smile. Whether that’s true or not, watching other people smile and make eye contact makes you feel good. Seeing them scowl and look away does the reverse.

This is true in doctors’ offices too. I learned this recently by being a patient.

I approached the front desk at my first visit. The lone receptionist was looking at some papers. I tried to get her attention. “Hello,” I said, “My name is ... ”

Still looking down, she shoved a clipboard across the counter. “Sign in,” she said. “And fill this out.” She handed me a sheaf of forms. “Leave it here when you’re done.” She was still looking away.

I sat in one of the waiting room chairs to work on the forms. I felt bad. As I watched the clerk ignore a succession of other patients, I asked myself why I felt so bad. First of all, it wasn’t personal; she was churlish to everyone. Second, what did this have to do with my visit? I was there to see the doctor, not his receptionist. Weren’t his skill and expertise what mattered?

True enough, but I still felt lousy. At later visits I took on the personal challenge of trying to force the clerk to make eye contact. I failed. In truth, her behavior colored my impression of the medical experience – mixed anyway – more than the medical outcome.

Sometimes I force myself to look at my own online reviews. The bad ones often focus on the alleged rudeness of my staff. It can be hard to tell from cranky patients whether their complaints are justified. But sometimes they are.

Management consultants know this. They teach employers that the customer experience has to do with more than the quality of the good or service provided. Even if the quarter-pounder is delicious, it may not taste that way if the burger-flipper is having a bad day and doesn’t know how to hide it.

So my office manager now trains our front-desk staff to be insistently cheery. This can be hard when patients are stacked three-deep, each with a form to scan, a credit card to swipe, a follow-up to book. But smile we have them do.

We don’t, however, have them recite a script when smiling. (“Make the scene! Wear sunscreen!”) We’re not up to that chapter in the customer-service handbook.

Who do you think we are? The town lake?

Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. Write to him at [email protected].

Recent developments regarding the nature of transmissible pathologic proteins in a variety of common neurodegenerative diseases have started to cause clinicians and public health experts to wonder if there is cause for concern.

A group from the National Hospital for Neurology & Neurosurgery at Queen Square, London, recently published a study presenting evidence that Alzheimer’s disease may have transmissible properties similar to traditionally regarded prion diseases such as Creutzfeldt-Jakob disease (Nature. 2015 Sep 10;525:247-50. doi:10.1038/nature15369). This conclusion was based upon the observation of cerebral and vascular amyloid-beta deposition in several patients who had received cadaveric growth hormone extracts ranging from 19 to 39 years earlier and who developed iatrogenic Creutzfeldt-Jakob disease (CJD). Amyloid deposition was also identified in the pituitary glands of patients with amyloid-beta pathology also felt to be iatrogenically transmitted.

This is not the first time, however, that analogies have been drawn between neurodegenerative diseases and prion-related diseases. Perhaps inspired by the evident connectivity of affected upper and lower motor neuronal populations in amyotrophic lateral sclerosis, previous investigators have sought cell-to-cell transmission of neurodegenerative pathology and have demonstrated this for amyloid as well as tau species in Alzheimer’s disease, and for synuclein species in Parkinson’s disease.

A recent article by Dr. Stanley Prusiner of the University of California, San Francisco, and his colleagues presented evidence that brain extracts from patients with multiple system atrophy (MSA) transmitted the characteristic MSA alpha-synuclein aggregates in the brains of transgenic mice as well as in cultured human embryonic kidney cells (Proc Natl Acad Sci U S A. 2015 Aug 31. doi:10.1073/pnas.1514475112).

An emerging theme from these recent and prior studies is that neurodegenerative diseases behave a lot like prion diseases, and although they follow a much slower time course, may spread through synaptic pathways as well as between people through prion-like mechanisms. CJD, while transmissible, is not “contagious,” and public messaging should draw this distinction in regard to neurodegenerative diseases. Nonetheless, further research is urgently needed given the implications of this work. Dr. Prusiner and his associates concluded, for example, that deep brain stimulation electrodes and related equipment should not be reused from Parkinson’s disease patients for fear of spreading the synucleinopathy from one person to another. Should there be restrictions with regard to any form of tissue transplantation or blood transfusion from patients with Parkinson’s disease or Alzheimer’s disease? Questions such as these need further clarification, and given the prevalence of these procedures, such research should be highly prioritized.

Dr. Caselli is professor of neurology at the Mayo Clinic, Scottsdale, Ariz. He also serves there as associate director and clinical core director of the Alzheimer’s Disease Center.

Recent developments regarding the nature of transmissible pathologic proteins in a variety of common neurodegenerative diseases have started to cause clinicians and public health experts to wonder if there is cause for concern.

A group from the National Hospital for Neurology & Neurosurgery at Queen Square, London, recently published a study presenting evidence that Alzheimer’s disease may have transmissible properties similar to traditionally regarded prion diseases such as Creutzfeldt-Jakob disease (Nature. 2015 Sep 10;525:247-50. doi:10.1038/nature15369). This conclusion was based upon the observation of cerebral and vascular amyloid-beta deposition in several patients who had received cadaveric growth hormone extracts ranging from 19 to 39 years earlier and who developed iatrogenic Creutzfeldt-Jakob disease (CJD). Amyloid deposition was also identified in the pituitary glands of patients with amyloid-beta pathology also felt to be iatrogenically transmitted.

This is not the first time, however, that analogies have been drawn between neurodegenerative diseases and prion-related diseases. Perhaps inspired by the evident connectivity of affected upper and lower motor neuronal populations in amyotrophic lateral sclerosis, previous investigators have sought cell-to-cell transmission of neurodegenerative pathology and have demonstrated this for amyloid as well as tau species in Alzheimer’s disease, and for synuclein species in Parkinson’s disease.

A recent article by Dr. Stanley Prusiner of the University of California, San Francisco, and his colleagues presented evidence that brain extracts from patients with multiple system atrophy (MSA) transmitted the characteristic MSA alpha-synuclein aggregates in the brains of transgenic mice as well as in cultured human embryonic kidney cells (Proc Natl Acad Sci U S A. 2015 Aug 31. doi:10.1073/pnas.1514475112).

An emerging theme from these recent and prior studies is that neurodegenerative diseases behave a lot like prion diseases, and although they follow a much slower time course, may spread through synaptic pathways as well as between people through prion-like mechanisms. CJD, while transmissible, is not “contagious,” and public messaging should draw this distinction in regard to neurodegenerative diseases. Nonetheless, further research is urgently needed given the implications of this work. Dr. Prusiner and his associates concluded, for example, that deep brain stimulation electrodes and related equipment should not be reused from Parkinson’s disease patients for fear of spreading the synucleinopathy from one person to another. Should there be restrictions with regard to any form of tissue transplantation or blood transfusion from patients with Parkinson’s disease or Alzheimer’s disease? Questions such as these need further clarification, and given the prevalence of these procedures, such research should be highly prioritized.

Dr. Caselli is professor of neurology at the Mayo Clinic, Scottsdale, Ariz. He also serves there as associate director and clinical core director of the Alzheimer’s Disease Center.

Recent developments regarding the nature of transmissible pathologic proteins in a variety of common neurodegenerative diseases have started to cause clinicians and public health experts to wonder if there is cause for concern.

A group from the National Hospital for Neurology & Neurosurgery at Queen Square, London, recently published a study presenting evidence that Alzheimer’s disease may have transmissible properties similar to traditionally regarded prion diseases such as Creutzfeldt-Jakob disease (Nature. 2015 Sep 10;525:247-50. doi:10.1038/nature15369). This conclusion was based upon the observation of cerebral and vascular amyloid-beta deposition in several patients who had received cadaveric growth hormone extracts ranging from 19 to 39 years earlier and who developed iatrogenic Creutzfeldt-Jakob disease (CJD). Amyloid deposition was also identified in the pituitary glands of patients with amyloid-beta pathology also felt to be iatrogenically transmitted.

This is not the first time, however, that analogies have been drawn between neurodegenerative diseases and prion-related diseases. Perhaps inspired by the evident connectivity of affected upper and lower motor neuronal populations in amyotrophic lateral sclerosis, previous investigators have sought cell-to-cell transmission of neurodegenerative pathology and have demonstrated this for amyloid as well as tau species in Alzheimer’s disease, and for synuclein species in Parkinson’s disease.

A recent article by Dr. Stanley Prusiner of the University of California, San Francisco, and his colleagues presented evidence that brain extracts from patients with multiple system atrophy (MSA) transmitted the characteristic MSA alpha-synuclein aggregates in the brains of transgenic mice as well as in cultured human embryonic kidney cells (Proc Natl Acad Sci U S A. 2015 Aug 31. doi:10.1073/pnas.1514475112).

An emerging theme from these recent and prior studies is that neurodegenerative diseases behave a lot like prion diseases, and although they follow a much slower time course, may spread through synaptic pathways as well as between people through prion-like mechanisms. CJD, while transmissible, is not “contagious,” and public messaging should draw this distinction in regard to neurodegenerative diseases. Nonetheless, further research is urgently needed given the implications of this work. Dr. Prusiner and his associates concluded, for example, that deep brain stimulation electrodes and related equipment should not be reused from Parkinson’s disease patients for fear of spreading the synucleinopathy from one person to another. Should there be restrictions with regard to any form of tissue transplantation or blood transfusion from patients with Parkinson’s disease or Alzheimer’s disease? Questions such as these need further clarification, and given the prevalence of these procedures, such research should be highly prioritized.

Dr. Caselli is professor of neurology at the Mayo Clinic, Scottsdale, Ariz. He also serves there as associate director and clinical core director of the Alzheimer’s Disease Center.

Recently I received a lengthy e-mail from a very worried woman. She claimed to be an established patient in my office, which I had no way of confirming because she did not sign her message. She asked many questions about sexually transmitted diseases and how they might affect her and a new boyfriend.

I was undecided on how to reply – or even whether to reply at all – so I queried several dozen dermatology colleagues around the country, as well as a few physician friends and acquaintances in other specialties.

Responses varied all over the map – from “I never answer patient e-mails,” to “What harm could it do, she’s better off getting correct answers from you than incorrect answers from some ‘advocacy’ web site” – and everything in between.

Clearly, this is a controversial issue which will only get more controversial in the future, so I decided to look at what has been published on the subject.

It turns out that as early as 1998, a group of investigators asked this same question and designed a study to address it. (Eysenbach and Diepgen: “Responses to unsolicited patient e-mail requests for medical advice on the World Wide Web. JAMA. 1998;280[15]:1333-5). Posing as a fictitious patient, they sent e-mails to random dermatologists describing an acute dermatological problem, tallied the responses they received, and followed up with a questionnaire to responders and nonresponders alike.

As with my informal survey, the authors found what they termed “a striking lack of consensus” on how to deal with this situation: Fifty percent responded to the fictitious patient’s e-mail. Of those, 31% refused to give advice without seeing the patient, but 59% offered a diagnosis, and a third of that group went on to provide specific advice about therapy. In response to the questionnaire, 28% said that they tended not to answer any patient e-mails, 24% said they usually replied with a standard message, and 24% said they answer each request individually. The authors concluded that “standards for physician response to unsolicited patient e-mail are needed.”

Indeed; but my own survey suggests that, 17 years later, there is still nothing resembling a consensus on this issue. In the interim, several groups, including the American Medical Informatics Association, Medem, and the AMA have proposed guidelines; but none have been generally accepted.

Until such time as that happens, it seems advisable for each individual practice to take the time to adopt its own guidelines. For ideas, take a look at the examples I’ve listed, plus any others you can find. When you’re done, consider running your list past your lawyer to make sure you haven’t forgotten anything, and that there are no peculiar requirements in your state.

Your guidelines may be very simple (if you decide never to answer any queries) or very complex, depending on your situation and personal philosophy. But all guidelines should cover such issues of authentication of patient correspondents, informed consent of those patients, licensing jurisdiction (if you receive e-mails from states in which you are not licensed), and above all, confidentiality.

Contrary to popular belief, the Health Insurance Portability and Accountability Act (HIPAA) does not prohibit such communication, nor require that it be encrypted. The HIPAA website says, “Patients may initiate communications with a provider using e-mail. If this situation occurs, the health care provider can assume (unless the patient has explicitly stated otherwise) that e-mail communications are acceptable to the individual.”

Still, if the lack of encryption and other privacy safeguards makes you (or your patients) uncomfortable, encryption software can be added to your practice’s e-mail system. Enli (www.enli.net), Sigaba (www.sigaba.com), Tumbleweed (www.axway.com), Zix (www.zixcorp.com), and many other vendors sell encryption packages. (As always, I have no financial interest in any product or enterprise mentioned in this column.)

But rather than simply encrypting your e-mail, consider adopting web-based messaging. Patients enter your web site and send a message using an electronic template that you design. You (or a designated staffer) will be notified by regular e-mail when messages are received, and you can post a reply on a page that can be accessed only by the patient. Besides enhancing privacy and security, you can state your guidelines in plain English to preclude any misunderstanding of what you will and will not address online.

Web-based messaging services can be freestanding or incorporated into existing secure websites. Medfusion (www.medfusion.net), and RelayHealth (www.relayhealth.com) are among the leading vendors of secure messaging services.

As for the e-mail query which triggered all this: I responded, but I told the patient I could not provide specific answers to such personal questions over the Internet, particularly when they were asked anonymously; but I would be happy to address her concerns in person, in my office.

And now, I’m writing my guidelines.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

Recently I received a lengthy e-mail from a very worried woman. She claimed to be an established patient in my office, which I had no way of confirming because she did not sign her message. She asked many questions about sexually transmitted diseases and how they might affect her and a new boyfriend.

I was undecided on how to reply – or even whether to reply at all – so I queried several dozen dermatology colleagues around the country, as well as a few physician friends and acquaintances in other specialties.

Responses varied all over the map – from “I never answer patient e-mails,” to “What harm could it do, she’s better off getting correct answers from you than incorrect answers from some ‘advocacy’ web site” – and everything in between.

Clearly, this is a controversial issue which will only get more controversial in the future, so I decided to look at what has been published on the subject.

It turns out that as early as 1998, a group of investigators asked this same question and designed a study to address it. (Eysenbach and Diepgen: “Responses to unsolicited patient e-mail requests for medical advice on the World Wide Web. JAMA. 1998;280[15]:1333-5). Posing as a fictitious patient, they sent e-mails to random dermatologists describing an acute dermatological problem, tallied the responses they received, and followed up with a questionnaire to responders and nonresponders alike.

As with my informal survey, the authors found what they termed “a striking lack of consensus” on how to deal with this situation: Fifty percent responded to the fictitious patient’s e-mail. Of those, 31% refused to give advice without seeing the patient, but 59% offered a diagnosis, and a third of that group went on to provide specific advice about therapy. In response to the questionnaire, 28% said that they tended not to answer any patient e-mails, 24% said they usually replied with a standard message, and 24% said they answer each request individually. The authors concluded that “standards for physician response to unsolicited patient e-mail are needed.”

Indeed; but my own survey suggests that, 17 years later, there is still nothing resembling a consensus on this issue. In the interim, several groups, including the American Medical Informatics Association, Medem, and the AMA have proposed guidelines; but none have been generally accepted.

Until such time as that happens, it seems advisable for each individual practice to take the time to adopt its own guidelines. For ideas, take a look at the examples I’ve listed, plus any others you can find. When you’re done, consider running your list past your lawyer to make sure you haven’t forgotten anything, and that there are no peculiar requirements in your state.

Your guidelines may be very simple (if you decide never to answer any queries) or very complex, depending on your situation and personal philosophy. But all guidelines should cover such issues of authentication of patient correspondents, informed consent of those patients, licensing jurisdiction (if you receive e-mails from states in which you are not licensed), and above all, confidentiality.

Contrary to popular belief, the Health Insurance Portability and Accountability Act (HIPAA) does not prohibit such communication, nor require that it be encrypted. The HIPAA website says, “Patients may initiate communications with a provider using e-mail. If this situation occurs, the health care provider can assume (unless the patient has explicitly stated otherwise) that e-mail communications are acceptable to the individual.”

Still, if the lack of encryption and other privacy safeguards makes you (or your patients) uncomfortable, encryption software can be added to your practice’s e-mail system. Enli (www.enli.net), Sigaba (www.sigaba.com), Tumbleweed (www.axway.com), Zix (www.zixcorp.com), and many other vendors sell encryption packages. (As always, I have no financial interest in any product or enterprise mentioned in this column.)

But rather than simply encrypting your e-mail, consider adopting web-based messaging. Patients enter your web site and send a message using an electronic template that you design. You (or a designated staffer) will be notified by regular e-mail when messages are received, and you can post a reply on a page that can be accessed only by the patient. Besides enhancing privacy and security, you can state your guidelines in plain English to preclude any misunderstanding of what you will and will not address online.

Web-based messaging services can be freestanding or incorporated into existing secure websites. Medfusion (www.medfusion.net), and RelayHealth (www.relayhealth.com) are among the leading vendors of secure messaging services.

As for the e-mail query which triggered all this: I responded, but I told the patient I could not provide specific answers to such personal questions over the Internet, particularly when they were asked anonymously; but I would be happy to address her concerns in person, in my office.

And now, I’m writing my guidelines.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

Recently I received a lengthy e-mail from a very worried woman. She claimed to be an established patient in my office, which I had no way of confirming because she did not sign her message. She asked many questions about sexually transmitted diseases and how they might affect her and a new boyfriend.

I was undecided on how to reply – or even whether to reply at all – so I queried several dozen dermatology colleagues around the country, as well as a few physician friends and acquaintances in other specialties.

Responses varied all over the map – from “I never answer patient e-mails,” to “What harm could it do, she’s better off getting correct answers from you than incorrect answers from some ‘advocacy’ web site” – and everything in between.

Clearly, this is a controversial issue which will only get more controversial in the future, so I decided to look at what has been published on the subject.

It turns out that as early as 1998, a group of investigators asked this same question and designed a study to address it. (Eysenbach and Diepgen: “Responses to unsolicited patient e-mail requests for medical advice on the World Wide Web. JAMA. 1998;280[15]:1333-5). Posing as a fictitious patient, they sent e-mails to random dermatologists describing an acute dermatological problem, tallied the responses they received, and followed up with a questionnaire to responders and nonresponders alike.

As with my informal survey, the authors found what they termed “a striking lack of consensus” on how to deal with this situation: Fifty percent responded to the fictitious patient’s e-mail. Of those, 31% refused to give advice without seeing the patient, but 59% offered a diagnosis, and a third of that group went on to provide specific advice about therapy. In response to the questionnaire, 28% said that they tended not to answer any patient e-mails, 24% said they usually replied with a standard message, and 24% said they answer each request individually. The authors concluded that “standards for physician response to unsolicited patient e-mail are needed.”

Indeed; but my own survey suggests that, 17 years later, there is still nothing resembling a consensus on this issue. In the interim, several groups, including the American Medical Informatics Association, Medem, and the AMA have proposed guidelines; but none have been generally accepted.

Until such time as that happens, it seems advisable for each individual practice to take the time to adopt its own guidelines. For ideas, take a look at the examples I’ve listed, plus any others you can find. When you’re done, consider running your list past your lawyer to make sure you haven’t forgotten anything, and that there are no peculiar requirements in your state.

Your guidelines may be very simple (if you decide never to answer any queries) or very complex, depending on your situation and personal philosophy. But all guidelines should cover such issues of authentication of patient correspondents, informed consent of those patients, licensing jurisdiction (if you receive e-mails from states in which you are not licensed), and above all, confidentiality.

Contrary to popular belief, the Health Insurance Portability and Accountability Act (HIPAA) does not prohibit such communication, nor require that it be encrypted. The HIPAA website says, “Patients may initiate communications with a provider using e-mail. If this situation occurs, the health care provider can assume (unless the patient has explicitly stated otherwise) that e-mail communications are acceptable to the individual.”

Still, if the lack of encryption and other privacy safeguards makes you (or your patients) uncomfortable, encryption software can be added to your practice’s e-mail system. Enli (www.enli.net), Sigaba (www.sigaba.com), Tumbleweed (www.axway.com), Zix (www.zixcorp.com), and many other vendors sell encryption packages. (As always, I have no financial interest in any product or enterprise mentioned in this column.)

But rather than simply encrypting your e-mail, consider adopting web-based messaging. Patients enter your web site and send a message using an electronic template that you design. You (or a designated staffer) will be notified by regular e-mail when messages are received, and you can post a reply on a page that can be accessed only by the patient. Besides enhancing privacy and security, you can state your guidelines in plain English to preclude any misunderstanding of what you will and will not address online.

Web-based messaging services can be freestanding or incorporated into existing secure websites. Medfusion (www.medfusion.net), and RelayHealth (www.relayhealth.com) are among the leading vendors of secure messaging services.

As for the e-mail query which triggered all this: I responded, but I told the patient I could not provide specific answers to such personal questions over the Internet, particularly when they were asked anonymously; but I would be happy to address her concerns in person, in my office.

And now, I’m writing my guidelines.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

Recently, I was amazed to see a small walk-in booth with a webcam, a monitor, and a curtain, offering telemedicine consults from the comfort of a service station on I-95. Pandora’s Box, I thought.

The robots are coming! Take a dip into popular science fiction if you don’t believe me. From Asimov to “Star Wars,” there are innumerable examples of aseptic, polite automatons providing prompt, unbiased, unfatigued medical care. People have always been enamored by such visions of the future. And booths like this are the gateway to that vision. As excited as I am about this tremendous advance and the potential it holds, I can’t help but feel that when this new frontier of medicine reaches fruition, we will have lost something, too.

Medical education is exacting, exciting, and at times, excruciating. But above all, the privileged experience of learning about the inner workings of the body is an innately human process. Looking back, it’s not syndromes, numbers, or dosages I remember, but the colorful spectrum of characters I encountered along the way. We’ve all met them – the funny, the quirky, the warm, the gentle, the stern, the phlegmatic, the intermittently explosive, the socially inept, the obliviously savant, and occasionally, the frankly sociopathic. They are the ones who teach us how the science of medicine connects with the art of healing. Our bedside manners and critical thinking processes are molded by the intercourse between the different types of personalities we encounter in our education.

Until the first Medibot 3000 is rolled out, doctors will be flawed, biased, and stressed humans. We deal with the same roller coaster journey through life as do our patients, but we accept a responsibility to be the caretakers of their health. Perhaps we do so not in spite of our faults, but all the better because of them. The human experience provides us with empathy. It ingrains within us unique insights and perspectives. It allows us to read between the lines of a patient’s statements. It pushes us to go beyond protocols when we need to, and it helps us create the trust that is the heart of the doctor-patient relationship.

Kintsugi is the Japanese art of fixing cracks along broken pottery with rare metals, thus creating unique and beautiful patterns which accentuate the character of the pot. It is part of a philosophy called wabi-sabi, which is all about embracing imperfection. I think they’re on to something there.

Patients are not vignettes. There is no peer-reviewed algorithm for being a good doctor. Not to say that these things are not important. They are crucial tools in our endeavor to improve our medical skills and knowledge – the bedrock upon which a career in medicine must be founded. But I hope that in our quest to improve outcomes, to remove suffering, and move toward the beckoning future, we still will have a place in medicine for human characteristics that define the act of healing, and for the philosophy of wabi-sabi. Bring the robots on, I say.

Dr. Behere was a pediatric resident at the Children’s Hospital at Dartmouth, Lebanon, New Hampshire, when he wrote this article. He is currently a first-year fellow in pediatric cardiology at the Nemours Cardiac Center at the Nemours/Alfred I. duPont Hospital for Children, Wilmington, Del. E-mail him at [email protected].

Recently, I was amazed to see a small walk-in booth with a webcam, a monitor, and a curtain, offering telemedicine consults from the comfort of a service station on I-95. Pandora’s Box, I thought.

The robots are coming! Take a dip into popular science fiction if you don’t believe me. From Asimov to “Star Wars,” there are innumerable examples of aseptic, polite automatons providing prompt, unbiased, unfatigued medical care. People have always been enamored by such visions of the future. And booths like this are the gateway to that vision. As excited as I am about this tremendous advance and the potential it holds, I can’t help but feel that when this new frontier of medicine reaches fruition, we will have lost something, too.

Medical education is exacting, exciting, and at times, excruciating. But above all, the privileged experience of learning about the inner workings of the body is an innately human process. Looking back, it’s not syndromes, numbers, or dosages I remember, but the colorful spectrum of characters I encountered along the way. We’ve all met them – the funny, the quirky, the warm, the gentle, the stern, the phlegmatic, the intermittently explosive, the socially inept, the obliviously savant, and occasionally, the frankly sociopathic. They are the ones who teach us how the science of medicine connects with the art of healing. Our bedside manners and critical thinking processes are molded by the intercourse between the different types of personalities we encounter in our education.

Until the first Medibot 3000 is rolled out, doctors will be flawed, biased, and stressed humans. We deal with the same roller coaster journey through life as do our patients, but we accept a responsibility to be the caretakers of their health. Perhaps we do so not in spite of our faults, but all the better because of them. The human experience provides us with empathy. It ingrains within us unique insights and perspectives. It allows us to read between the lines of a patient’s statements. It pushes us to go beyond protocols when we need to, and it helps us create the trust that is the heart of the doctor-patient relationship.

Kintsugi is the Japanese art of fixing cracks along broken pottery with rare metals, thus creating unique and beautiful patterns which accentuate the character of the pot. It is part of a philosophy called wabi-sabi, which is all about embracing imperfection. I think they’re on to something there.

Patients are not vignettes. There is no peer-reviewed algorithm for being a good doctor. Not to say that these things are not important. They are crucial tools in our endeavor to improve our medical skills and knowledge – the bedrock upon which a career in medicine must be founded. But I hope that in our quest to improve outcomes, to remove suffering, and move toward the beckoning future, we still will have a place in medicine for human characteristics that define the act of healing, and for the philosophy of wabi-sabi. Bring the robots on, I say.

Dr. Behere was a pediatric resident at the Children’s Hospital at Dartmouth, Lebanon, New Hampshire, when he wrote this article. He is currently a first-year fellow in pediatric cardiology at the Nemours Cardiac Center at the Nemours/Alfred I. duPont Hospital for Children, Wilmington, Del. E-mail him at [email protected].

Recently, I was amazed to see a small walk-in booth with a webcam, a monitor, and a curtain, offering telemedicine consults from the comfort of a service station on I-95. Pandora’s Box, I thought.

The robots are coming! Take a dip into popular science fiction if you don’t believe me. From Asimov to “Star Wars,” there are innumerable examples of aseptic, polite automatons providing prompt, unbiased, unfatigued medical care. People have always been enamored by such visions of the future. And booths like this are the gateway to that vision. As excited as I am about this tremendous advance and the potential it holds, I can’t help but feel that when this new frontier of medicine reaches fruition, we will have lost something, too.

Medical education is exacting, exciting, and at times, excruciating. But above all, the privileged experience of learning about the inner workings of the body is an innately human process. Looking back, it’s not syndromes, numbers, or dosages I remember, but the colorful spectrum of characters I encountered along the way. We’ve all met them – the funny, the quirky, the warm, the gentle, the stern, the phlegmatic, the intermittently explosive, the socially inept, the obliviously savant, and occasionally, the frankly sociopathic. They are the ones who teach us how the science of medicine connects with the art of healing. Our bedside manners and critical thinking processes are molded by the intercourse between the different types of personalities we encounter in our education.

Until the first Medibot 3000 is rolled out, doctors will be flawed, biased, and stressed humans. We deal with the same roller coaster journey through life as do our patients, but we accept a responsibility to be the caretakers of their health. Perhaps we do so not in spite of our faults, but all the better because of them. The human experience provides us with empathy. It ingrains within us unique insights and perspectives. It allows us to read between the lines of a patient’s statements. It pushes us to go beyond protocols when we need to, and it helps us create the trust that is the heart of the doctor-patient relationship.

Kintsugi is the Japanese art of fixing cracks along broken pottery with rare metals, thus creating unique and beautiful patterns which accentuate the character of the pot. It is part of a philosophy called wabi-sabi, which is all about embracing imperfection. I think they’re on to something there.

Patients are not vignettes. There is no peer-reviewed algorithm for being a good doctor. Not to say that these things are not important. They are crucial tools in our endeavor to improve our medical skills and knowledge – the bedrock upon which a career in medicine must be founded. But I hope that in our quest to improve outcomes, to remove suffering, and move toward the beckoning future, we still will have a place in medicine for human characteristics that define the act of healing, and for the philosophy of wabi-sabi. Bring the robots on, I say.

Dr. Behere was a pediatric resident at the Children’s Hospital at Dartmouth, Lebanon, New Hampshire, when he wrote this article. He is currently a first-year fellow in pediatric cardiology at the Nemours Cardiac Center at the Nemours/Alfred I. duPont Hospital for Children, Wilmington, Del. E-mail him at [email protected].