Young adults who inject drugs and are infected with hepatitis C virus “face unique barriers to HCV testing, counseling, and treatment,” according to Margie R. Skeer, ScD, of Tufts University, Boston, and her fellow researchers.

©andrewsafonov/Thinkstock

Dr. Skeer and her colleagues found five themes in 24 in-depth interviews with people aged 22-30 years who inject drugs and have HCV infection. At the time of the interviews, none of the patients had received the newer HCV treatment regimens (Drug Alcohol Depend. 2018 Sep 1;190:246-54).

These themes captured the knowledge of and experience of HCV along the continuum of care:

1. Deservingness of HCV treatment and stigma.

2. Dissatisfaction with provider interactions.

3. Perceived lack of referral to treatment and care continuity.

4. Disincentives around HCV treatment for PWID.

5. Perceived need for treatment.

The interviewees were largely uninformed about HCV prior to diagnosis and reported learning more about the virus after their diagnosis. They also tended to affirm the belief that they did not deserve treatment. They felt stigmatized by insurance companies and clinicians, thereby reducing their engagement in the care continuum. And, at the time, insurance companies enforced “sobriety” restrictions dictating the length of time patients had to be off drugs before qualifying for HCV treatment. In the words of one interviewee: “[Caregivers] have a big stigma when it comes to addicts. ... Their whole demeanor changes. They rush you, they slam things, they are very impatient with you, and it is very saddening to see.”

Interviewees reported no or incomplete referrals or being given pamphlets and flyers. They reported little follow-up as to whether they sought additional care, and experienced a lack of confidence from medical professionals that they could be counted on to adhere to an HCV treatment regimen.

Interviewees stated that injection drug use and HCV are inevitably linked, and that IV drug users will eventually contract HCV infections.

“Hep C’s no big deal, Hep C’s like the common cold for the junkie. ... It might take 5 years away from your, you know, life but, you know, we’re not even gonna live that long anyways, so who cares about it anyway,” remarked a 28-year old woman, who was not currently injecting drugs.

The study authors said there is an increased need to provide patient-oriented care for young injection drug users and described the potential benefits of some insurance companies reducing their sobriety and disease severity restrictions.

“Reducing stigma among healthcare professionals, which cuts across the different levels of the HCV care continuum, improving referral patterns and continuity of care, better informing people about their HCV status through patient-oriented testing and disclosure experiences, and reducing perceptions of personal responsibility for disease are crucial next steps to increasing treatment as prevention,” Dr. Skeer and her colleagues concluded.

The authors reported that they had no conflicts of interest.

[email protected]

Young adults who inject drugs and are infected with hepatitis C virus “face unique barriers to HCV testing, counseling, and treatment,” according to Margie R. Skeer, ScD, of Tufts University, Boston, and her fellow researchers.

©andrewsafonov/Thinkstock

Dr. Skeer and her colleagues found five themes in 24 in-depth interviews with people aged 22-30 years who inject drugs and have HCV infection. At the time of the interviews, none of the patients had received the newer HCV treatment regimens (Drug Alcohol Depend. 2018 Sep 1;190:246-54).

These themes captured the knowledge of and experience of HCV along the continuum of care:

1. Deservingness of HCV treatment and stigma.

2. Dissatisfaction with provider interactions.

3. Perceived lack of referral to treatment and care continuity.

4. Disincentives around HCV treatment for PWID.

5. Perceived need for treatment.

The interviewees were largely uninformed about HCV prior to diagnosis and reported learning more about the virus after their diagnosis. They also tended to affirm the belief that they did not deserve treatment. They felt stigmatized by insurance companies and clinicians, thereby reducing their engagement in the care continuum. And, at the time, insurance companies enforced “sobriety” restrictions dictating the length of time patients had to be off drugs before qualifying for HCV treatment. In the words of one interviewee: “[Caregivers] have a big stigma when it comes to addicts. ... Their whole demeanor changes. They rush you, they slam things, they are very impatient with you, and it is very saddening to see.”

Interviewees reported no or incomplete referrals or being given pamphlets and flyers. They reported little follow-up as to whether they sought additional care, and experienced a lack of confidence from medical professionals that they could be counted on to adhere to an HCV treatment regimen.

Interviewees stated that injection drug use and HCV are inevitably linked, and that IV drug users will eventually contract HCV infections.

“Hep C’s no big deal, Hep C’s like the common cold for the junkie. ... It might take 5 years away from your, you know, life but, you know, we’re not even gonna live that long anyways, so who cares about it anyway,” remarked a 28-year old woman, who was not currently injecting drugs.

The study authors said there is an increased need to provide patient-oriented care for young injection drug users and described the potential benefits of some insurance companies reducing their sobriety and disease severity restrictions.

“Reducing stigma among healthcare professionals, which cuts across the different levels of the HCV care continuum, improving referral patterns and continuity of care, better informing people about their HCV status through patient-oriented testing and disclosure experiences, and reducing perceptions of personal responsibility for disease are crucial next steps to increasing treatment as prevention,” Dr. Skeer and her colleagues concluded.

The authors reported that they had no conflicts of interest.

[email protected]

Young adults who inject drugs and are infected with hepatitis C virus “face unique barriers to HCV testing, counseling, and treatment,” according to Margie R. Skeer, ScD, of Tufts University, Boston, and her fellow researchers.

©andrewsafonov/Thinkstock

Dr. Skeer and her colleagues found five themes in 24 in-depth interviews with people aged 22-30 years who inject drugs and have HCV infection. At the time of the interviews, none of the patients had received the newer HCV treatment regimens (Drug Alcohol Depend. 2018 Sep 1;190:246-54).

These themes captured the knowledge of and experience of HCV along the continuum of care:

1. Deservingness of HCV treatment and stigma.

2. Dissatisfaction with provider interactions.

3. Perceived lack of referral to treatment and care continuity.

4. Disincentives around HCV treatment for PWID.

5. Perceived need for treatment.

The interviewees were largely uninformed about HCV prior to diagnosis and reported learning more about the virus after their diagnosis. They also tended to affirm the belief that they did not deserve treatment. They felt stigmatized by insurance companies and clinicians, thereby reducing their engagement in the care continuum. And, at the time, insurance companies enforced “sobriety” restrictions dictating the length of time patients had to be off drugs before qualifying for HCV treatment. In the words of one interviewee: “[Caregivers] have a big stigma when it comes to addicts. ... Their whole demeanor changes. They rush you, they slam things, they are very impatient with you, and it is very saddening to see.”

Interviewees reported no or incomplete referrals or being given pamphlets and flyers. They reported little follow-up as to whether they sought additional care, and experienced a lack of confidence from medical professionals that they could be counted on to adhere to an HCV treatment regimen.

Interviewees stated that injection drug use and HCV are inevitably linked, and that IV drug users will eventually contract HCV infections.

“Hep C’s no big deal, Hep C’s like the common cold for the junkie. ... It might take 5 years away from your, you know, life but, you know, we’re not even gonna live that long anyways, so who cares about it anyway,” remarked a 28-year old woman, who was not currently injecting drugs.

The study authors said there is an increased need to provide patient-oriented care for young injection drug users and described the potential benefits of some insurance companies reducing their sobriety and disease severity restrictions.

“Reducing stigma among healthcare professionals, which cuts across the different levels of the HCV care continuum, improving referral patterns and continuity of care, better informing people about their HCV status through patient-oriented testing and disclosure experiences, and reducing perceptions of personal responsibility for disease are crucial next steps to increasing treatment as prevention,” Dr. Skeer and her colleagues concluded.

The authors reported that they had no conflicts of interest.

[email protected]

LAKE TAHOE, CALIF. – Children experience a wide range of cutaneous manifestations of immunosuppression, including atopic dermatitis (AD), skin cancer, and side effects of vemurafenib treatment.

In a presentation on the cutaneous sequelae of different immunosuppressive regimens at the annual meeting of the Society for Pediatric Dermatology, Carrie C. Coughlin, MD, opened with a discussion of AD triggered by the tumor necrosis factor (TNF) blocker infliximab, especially in the setting of therapy for Crohn’s disease. “In this patient population you often think of psoriasis as a consequence of infliximab and other TNF therapies,” said Dr. Coughlin, a pediatric dermatologist at Washington University, St. Louis. “But you can also get true atopic dermatitis with infliximab as well. Who’s more at risk for this? Patients with Crohn’s disease seem to be. Most of the literature is in adults, but there are a few series of children. In a series of children looking at cutaneous sequelae of infliximab therapy, about 20% of cutaneous eruptions were atopic dermatitis. I think it’s a great opportunity for us in dermatology to do a more research in this area.”

Some researchers have proposed that atopic disease could be a marker of over-suppression of TNF-alpha in young Crohn’s disease patients on infliximab (Inflamm Bowel Dis. 2014; 20[8]:1309-15). “One question you could ask is, could these patients actually tolerate a dose reduction?” Dr. Coughlin said. She promoted the role of dermatologists in working at managing side effects to keep patients on medications helping their GI disease, but acknowledged this is not always possible.

Doug Brunk/MDedge News

[email protected]

LAKE TAHOE, CALIF. – Children experience a wide range of cutaneous manifestations of immunosuppression, including atopic dermatitis (AD), skin cancer, and side effects of vemurafenib treatment.

In a presentation on the cutaneous sequelae of different immunosuppressive regimens at the annual meeting of the Society for Pediatric Dermatology, Carrie C. Coughlin, MD, opened with a discussion of AD triggered by the tumor necrosis factor (TNF) blocker infliximab, especially in the setting of therapy for Crohn’s disease. “In this patient population you often think of psoriasis as a consequence of infliximab and other TNF therapies,” said Dr. Coughlin, a pediatric dermatologist at Washington University, St. Louis. “But you can also get true atopic dermatitis with infliximab as well. Who’s more at risk for this? Patients with Crohn’s disease seem to be. Most of the literature is in adults, but there are a few series of children. In a series of children looking at cutaneous sequelae of infliximab therapy, about 20% of cutaneous eruptions were atopic dermatitis. I think it’s a great opportunity for us in dermatology to do a more research in this area.”

Some researchers have proposed that atopic disease could be a marker of over-suppression of TNF-alpha in young Crohn’s disease patients on infliximab (Inflamm Bowel Dis. 2014; 20[8]:1309-15). “One question you could ask is, could these patients actually tolerate a dose reduction?” Dr. Coughlin said. She promoted the role of dermatologists in working at managing side effects to keep patients on medications helping their GI disease, but acknowledged this is not always possible.

Doug Brunk/MDedge News

[email protected]

LAKE TAHOE, CALIF. – Children experience a wide range of cutaneous manifestations of immunosuppression, including atopic dermatitis (AD), skin cancer, and side effects of vemurafenib treatment.

In a presentation on the cutaneous sequelae of different immunosuppressive regimens at the annual meeting of the Society for Pediatric Dermatology, Carrie C. Coughlin, MD, opened with a discussion of AD triggered by the tumor necrosis factor (TNF) blocker infliximab, especially in the setting of therapy for Crohn’s disease. “In this patient population you often think of psoriasis as a consequence of infliximab and other TNF therapies,” said Dr. Coughlin, a pediatric dermatologist at Washington University, St. Louis. “But you can also get true atopic dermatitis with infliximab as well. Who’s more at risk for this? Patients with Crohn’s disease seem to be. Most of the literature is in adults, but there are a few series of children. In a series of children looking at cutaneous sequelae of infliximab therapy, about 20% of cutaneous eruptions were atopic dermatitis. I think it’s a great opportunity for us in dermatology to do a more research in this area.”

Some researchers have proposed that atopic disease could be a marker of over-suppression of TNF-alpha in young Crohn’s disease patients on infliximab (Inflamm Bowel Dis. 2014; 20[8]:1309-15). “One question you could ask is, could these patients actually tolerate a dose reduction?” Dr. Coughlin said. She promoted the role of dermatologists in working at managing side effects to keep patients on medications helping their GI disease, but acknowledged this is not always possible.

Doug Brunk/MDedge News

[email protected]

When a child presents with hair loss, don’t rule out issues related to genetics and structural abnormalities of the hair itself, according to Maria Hordinsky, MD, of the University of Minnesota, Minneapolis.

The ectodermal dysplasias are a heterogeneous group of disorders in which a main feature is the absent, incomplete, or delayed development of one or more of the appendages derived from ectoderm, such as the hair follicle, Dr. Hordinsky said in a presentation at Skin Disease Education Foundation’s Women’s & Pediatric Dermatology Seminar.

Patients with pure hair and nail ectodermal dysplasia generally present with absent or sparse eyebrows and eyelashes, as well as follicular papules on the scalp and fragile, irregular hair, Dr. Hordinsky said. The condition is caused by a mutation in a gene associated with the production of keratin. In another rare form of hereditary hair loss – hypotrichosis simplex – patients are born with normal hair but lose it gradually from the scalp during the middle of the first decade of life.

The inability to grow long hair characterizes short anagen syndrome, a congenital disorder not to be confused with loose anagen syndrome, Dr. Hordinsky said. Patients with short anagen syndrome experience an idiopathic short anagen phase and as a result, an increased number of hairs in the telogen phase. Children with short anagen syndrome have unusually short hair in early childhood. “Parents typically complain that their children exhibit short hair even though they have never had a haircut,” she explained.

Trichothiodystrophy, a rare autosomal recessive disease, is distinguished by hair that is brittle and sulfur deficient, Dr. Hordinsky said. She cited a review of 112 patients with trichothiodystrophy in which additional distinguishing features included developmental delay/intellectual impairment (86%), short stature (73%), and ichthyosis (65%).

Some cases of hair loss in children have a structural basis, Dr. Hordinsky noted. Structural hair abnormalities include fractures of the hair shaft, extraneous matter on the hair shaft, and hair shaft irregularities such as coiling or twisting, she said.

In trichoptilosis, extensive cuticle loss results in fraying and splitting of the hair shaft, while in patients with trichoclasis, a fractured hair is splinted by a partially intact cuticle.

In trichorrhexis nodosa, the most common type of structural hair abnormality, “intact nodes [of hair] resemble two paintbrushes thrust together,” Dr. Hordinsky explained. Trichorrhexis nodosa may be congenital or acquired, and occurs in children with mental retardation and argininosuccinic aciduria, she said.

A hair shaft abnormality is the culprit behind uncombable hair syndrome, which can be inherited or can occur sporadically, Dr. Hordinsky said. The key feature of the condition is unruly hair caused by a distinctive hair shaft defect, “possibly related to an abnormality in the inner root sheath.” Abnormal hairs usually become apparent at about 3-4 years of age, but eyebrows and eyelashes appear normal. Many patients have a silvery blonde tint to their hair because of how the abnormal hairs reflect light, she said.

Dr. Hordinsky is a consultant for P&G, Concert, Cassiopea, and BioAZ; and receives grant/research support from Aclaris, Allergan, and the National Alopecia Areata Foundation. SDEF and this news organization are owned by Frontline Medical Communications.

When a child presents with hair loss, don’t rule out issues related to genetics and structural abnormalities of the hair itself, according to Maria Hordinsky, MD, of the University of Minnesota, Minneapolis.

The ectodermal dysplasias are a heterogeneous group of disorders in which a main feature is the absent, incomplete, or delayed development of one or more of the appendages derived from ectoderm, such as the hair follicle, Dr. Hordinsky said in a presentation at Skin Disease Education Foundation’s Women’s & Pediatric Dermatology Seminar.

Patients with pure hair and nail ectodermal dysplasia generally present with absent or sparse eyebrows and eyelashes, as well as follicular papules on the scalp and fragile, irregular hair, Dr. Hordinsky said. The condition is caused by a mutation in a gene associated with the production of keratin. In another rare form of hereditary hair loss – hypotrichosis simplex – patients are born with normal hair but lose it gradually from the scalp during the middle of the first decade of life.

The inability to grow long hair characterizes short anagen syndrome, a congenital disorder not to be confused with loose anagen syndrome, Dr. Hordinsky said. Patients with short anagen syndrome experience an idiopathic short anagen phase and as a result, an increased number of hairs in the telogen phase. Children with short anagen syndrome have unusually short hair in early childhood. “Parents typically complain that their children exhibit short hair even though they have never had a haircut,” she explained.

Trichothiodystrophy, a rare autosomal recessive disease, is distinguished by hair that is brittle and sulfur deficient, Dr. Hordinsky said. She cited a review of 112 patients with trichothiodystrophy in which additional distinguishing features included developmental delay/intellectual impairment (86%), short stature (73%), and ichthyosis (65%).

Some cases of hair loss in children have a structural basis, Dr. Hordinsky noted. Structural hair abnormalities include fractures of the hair shaft, extraneous matter on the hair shaft, and hair shaft irregularities such as coiling or twisting, she said.

In trichoptilosis, extensive cuticle loss results in fraying and splitting of the hair shaft, while in patients with trichoclasis, a fractured hair is splinted by a partially intact cuticle.

In trichorrhexis nodosa, the most common type of structural hair abnormality, “intact nodes [of hair] resemble two paintbrushes thrust together,” Dr. Hordinsky explained. Trichorrhexis nodosa may be congenital or acquired, and occurs in children with mental retardation and argininosuccinic aciduria, she said.

A hair shaft abnormality is the culprit behind uncombable hair syndrome, which can be inherited or can occur sporadically, Dr. Hordinsky said. The key feature of the condition is unruly hair caused by a distinctive hair shaft defect, “possibly related to an abnormality in the inner root sheath.” Abnormal hairs usually become apparent at about 3-4 years of age, but eyebrows and eyelashes appear normal. Many patients have a silvery blonde tint to their hair because of how the abnormal hairs reflect light, she said.

Dr. Hordinsky is a consultant for P&G, Concert, Cassiopea, and BioAZ; and receives grant/research support from Aclaris, Allergan, and the National Alopecia Areata Foundation. SDEF and this news organization are owned by Frontline Medical Communications.

When a child presents with hair loss, don’t rule out issues related to genetics and structural abnormalities of the hair itself, according to Maria Hordinsky, MD, of the University of Minnesota, Minneapolis.

The ectodermal dysplasias are a heterogeneous group of disorders in which a main feature is the absent, incomplete, or delayed development of one or more of the appendages derived from ectoderm, such as the hair follicle, Dr. Hordinsky said in a presentation at Skin Disease Education Foundation’s Women’s & Pediatric Dermatology Seminar.

Patients with pure hair and nail ectodermal dysplasia generally present with absent or sparse eyebrows and eyelashes, as well as follicular papules on the scalp and fragile, irregular hair, Dr. Hordinsky said. The condition is caused by a mutation in a gene associated with the production of keratin. In another rare form of hereditary hair loss – hypotrichosis simplex – patients are born with normal hair but lose it gradually from the scalp during the middle of the first decade of life.

The inability to grow long hair characterizes short anagen syndrome, a congenital disorder not to be confused with loose anagen syndrome, Dr. Hordinsky said. Patients with short anagen syndrome experience an idiopathic short anagen phase and as a result, an increased number of hairs in the telogen phase. Children with short anagen syndrome have unusually short hair in early childhood. “Parents typically complain that their children exhibit short hair even though they have never had a haircut,” she explained.

Trichothiodystrophy, a rare autosomal recessive disease, is distinguished by hair that is brittle and sulfur deficient, Dr. Hordinsky said. She cited a review of 112 patients with trichothiodystrophy in which additional distinguishing features included developmental delay/intellectual impairment (86%), short stature (73%), and ichthyosis (65%).

Some cases of hair loss in children have a structural basis, Dr. Hordinsky noted. Structural hair abnormalities include fractures of the hair shaft, extraneous matter on the hair shaft, and hair shaft irregularities such as coiling or twisting, she said.

In trichoptilosis, extensive cuticle loss results in fraying and splitting of the hair shaft, while in patients with trichoclasis, a fractured hair is splinted by a partially intact cuticle.

In trichorrhexis nodosa, the most common type of structural hair abnormality, “intact nodes [of hair] resemble two paintbrushes thrust together,” Dr. Hordinsky explained. Trichorrhexis nodosa may be congenital or acquired, and occurs in children with mental retardation and argininosuccinic aciduria, she said.

A hair shaft abnormality is the culprit behind uncombable hair syndrome, which can be inherited or can occur sporadically, Dr. Hordinsky said. The key feature of the condition is unruly hair caused by a distinctive hair shaft defect, “possibly related to an abnormality in the inner root sheath.” Abnormal hairs usually become apparent at about 3-4 years of age, but eyebrows and eyelashes appear normal. Many patients have a silvery blonde tint to their hair because of how the abnormal hairs reflect light, she said.

Dr. Hordinsky is a consultant for P&G, Concert, Cassiopea, and BioAZ; and receives grant/research support from Aclaris, Allergan, and the National Alopecia Areata Foundation. SDEF and this news organization are owned by Frontline Medical Communications.

About Research in Context

In this article, the authors of recent scholarship have been asked to discuss the implications of their research on federal health care providers and specifically the veteran and active-duty service member patient populations. Because the article does not include new research and cannot be blinded, it has undergone an abbreviated peer review process. The original article can be found at Sullivan DR, Forsberg CW, Ganzini L, et al. Longitudinal changes in depression symptoms and survival among patients with lung cancer: a national cohort assessment. J Clin Oncol. 2016;34(33):3984-3991.

Although depression is common among patients with cancer, patients with lung cancer are at particularly high risk. The prevalence of major depressive disorder (MDD) among patients with cancer can be as high as 13%, whereas up to 44% of patients with lung cancer experience depression symptoms at some point following their cancer diagnosis.^1-3 These estimates are consistently higher than those of other types of cancer, possibly related to the stigma of the disease and the associated morbidity and mortality that are its hallmarks.^4-8 This potentially life-threatening cancer diagnosis often evokes psychological distress; however, additional stressors contribute to the development of depression, including the effects of chemotherapeutic agents, surgical procedures, radiotherapy, and the consequences of physical symptoms and paraneoplastic syndromes.

In addition to the crippling effects of comorbid depression on patients’ quality of life (QOL), severe and persistent depression among patients with cancer is associated with prolonged hospital stays, worse treatment adherence, physical distress and pain, and increased desire for hastened death.^9-11 During treatment, depression can amplify physical symptoms and interfere with effective coping.^12,13

Depression also is likely a significant factor for the risk of suicide, which is 4 times higher in patients with lung cancer than that of the general population.¹⁴ Most important, as our recent study demonstrated, depression that develops at cancer diagnosis or during cancer treatment may contribute to worse survival. This effect was strongest among patients with early stage disease, in other words, the patients who are most likely to achieve cure.³ This association with early stage disease also has been observed in a strictly veteran population from the northwest U.S.¹⁵

Another key finding of our study was the similar survival among patients who experienced a remission of their depression and those who were never depressed. This finding reinforces the importance of effective depression treatment, which has the potential to reduce depression-related mortality; however, depression treatment was not fully captured and could not be directly compared in our study. Unfortunately, comorbid depression often goes undiagnosed and untreated in cancer patients as they report unmet emotional needs and a desire for psychological support during and after completion of cancer treatment.^16,17

Given the general lack of depression treatment that occurs in patients with cancer, the negative consequences of depression can be sustained well into survivorship—defined clinically as someone who is free of any sign of cancer for 5 years. Cancer survivors frequently report fatigue, mood disturbance, sleep disruption, pain, and cognitive limitations that significantly impact QOL and are associated with disability and increased health care use.¹⁸ These symptoms likely are intertwined with and contribute to the development and persistence of depression. The ramifications of untreated depression on long-term cancer survivor outcomes are not completely understood, as few high-quality studies of depression in cancer survivors exist. However, in a mixed group of patients with cancer, there was a 2-fold risk of mortality in survivors with depression symptoms when these patients were assessed from 1 to 10 years into survivorship.¹⁹ The impact of depression on cancer survivorship is an important aspect of cancer care that deserves significantly more attention from both a research and clinical perspective.

Special Considerations for Veterans

There is a higher prevalence of mental health diagnoses in veterans than that in the general population, and depressive disorders are the most common.^20-22 According to the VA National Registry for Depression, 11% of veterans aged ≥ 65 years have a diagnosis of MDD, a rate more than twice that in the general population of a similar age.²³ However, the actual rate of depression among veterans may be even higher, as studies suggest depression is underdiagnosed in the veteran population.²⁴ In addition to depression, veterans experience other disabling psychological illnesses, such as posttraumatic stress disorder (PTSD) related to deployment and combat duty or combat-related injuries, such as traumatic brain injuries. The negative consequences of PTSD on cancer outcomes are largely unexplored, but PTSD can contribute to increased health care utilization and costs.^25,26 A similar psychological construct, cancer-related posttraumatic stress (PTS), which develops as a result of a cancer diagnosis or treatment, is associated with missed medical appointments and procedures, which could impact survival.²⁷

Depression Screening and Treatment

Given the negative consequences of comorbid mental illness, professional oncology societies have started developing guidelines regarding the assessments and care of patients with cancer who are experiencing symptoms of depression and/or anxiety.^11,28,29 Among these, the American Society of Clinical Oncology (ASCO) has adapted the Pan-Canadian Practice Guideline on Screening, Assessment, and Care of Psychosocial Distress (Depression, Anxiety) in Adults With Cancer.²⁸ Per ASCO, the target audience for these guidelines is health care providers (eg, medical, surgical, and radiation oncologists; psychiatrists; psychologists; primary care providers; nurses; and others involved in the delivery of care for adults with cancer) as well as patients with cancer and their family members and caregivers.²⁸ These guidelines address the optimum screening, assessment, and psychosocial-supportive care interventions for adults with cancer who are identified as experiencing symptoms of depression. Among the most imperative recommendations are periodic assessments across the trajectory of cancer care, including after cure, as well as employing institutional and community resources for depression treatment.

In clinical practice in a VA setting, implementing these guidelines might involve various interventions. First, it is vital for providers to conduct depression screening during periodic health care encounters. Given the high prevalence of depression in patients with lung cancer, we suggest using the 9-item Patient Health Questionnaire (PHQ-9) as an initial screening tool.³⁰ Unlike the abridged 2-item PHQ-2 commonly used in the VA, the PHQ-9 provides an assessment of the full range of depressive symptoms. An elevated PHQ-9 score (≥ 10) is consistent with a major depressive episode and should trigger next steps.³⁰

Once clinically significant depression is identified, initiation of treatment should occur next. The VA is well suited to assist and support non-mental health clinicians—particularly primary care—in treatment initiation and monitoring. This model of partnership is frequently called collaborative care, or integrated care, and it is well positioned to help patients with lung cancer with concomitant depression. In the VA, this model of care is called primary care-mental healthintegration (PC-MHI). One PC-MHI resource is called TIDES (Translating Initiatives for Depression into Effective Solutions), and when a patient is referred, a mental health nurse care manager helps to track the patients’ antidepressant adherence and treatment response while reporting results to primary care clinicians, who are generally responsible for initiating and continuing the antidepressant prescription. For patients preferring nonpharmacologic approaches or for whom an antidepressant may be contraindicated, PC-MHI can provide other assistance. For example, psychologists working in PC-MHI are equipped to provide a brief course of cognitive behavioral therapy sessions, another first-line, evidence-based treatment for clinical depression.

Clinician follow-up to ensure patient adherence, response, and satisfaction, and to adjust treatment as needed is essential. Besides ongoing coordination with PC-MHI services, including mental health clinicians as part of multidisciplinary cancer clinics could offer substantial added value to patients’ comprehensive cancer care. Indeed, the initiation of multicomponent depression care has been shown to improve QOL and role functioning in patients with cancer.³¹ Besides the established benefits on QOL, patients with lung cancer who achieve depression symptom remission also may enjoy a significant survival benefit over patients whose depression symptoms remain untreated during lung cancer treatment as our study suggests.³

Conclusion

Depression is a common comorbid disease among patients with lung cancer with important negative implications for QOL and survival. When it occurs after a cancer diagnosis, depression is expected to impact all phases of a patient’s life through treatment and survivorshi —ultimately affecting long-term survival. Veterans may be at particularly high risk given the increased prevalence of mental illness, including depression and PTSD in this group compared with that of the general population. Early detection and prompt treatment can promote depression remission, prevent relapse, and reduce the eventual emotional and financial burden of the disease. This approach may ultimately diminish the prevalence and persistence of depression symptoms and decrease the associated negative effects of this disease on patients with lung cancer.

The importance of integrated systems of depression treatment for patients with cancer as part of comprehensive cancer care cannot be overstated. Development and implementation of these systems should be a priority of lung cancer clinicians and treatment centers. The integrated system within the VA is well positioned to be a leader in this area, and VA clinicians who care for patients with lung cancer are encouraged to take advantage of available mental health resources. Additional research is urgently needed to explore optimal implementation of depression screening and subsequent treatment delivery to improve cancer patient outcomes in VA and non-VA health care settings.

Acknowledgments
This project was supported in part by the National Cancer Institute of the National Institutes of Health under award K07CA190706 to Dr. Sullivan, a Career Development Award from the Veterans Health Administration Health Service Research and Development (CDA 14-428) to Dr. Teo and the HSR&D Center to Improve Veteran Involvement in Care (CIVIC) (CIN 13-404) at the VA Portland Health Care System.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The VA had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies.

Click here to read the digital edition. 

About Research in Context

In this article, the authors of recent scholarship have been asked to discuss the implications of their research on federal health care providers and specifically the veteran and active-duty service member patient populations. Because the article does not include new research and cannot be blinded, it has undergone an abbreviated peer review process. The original article can be found at Sullivan DR, Forsberg CW, Ganzini L, et al. Longitudinal changes in depression symptoms and survival among patients with lung cancer: a national cohort assessment. J Clin Oncol. 2016;34(33):3984-3991.

Although depression is common among patients with cancer, patients with lung cancer are at particularly high risk. The prevalence of major depressive disorder (MDD) among patients with cancer can be as high as 13%, whereas up to 44% of patients with lung cancer experience depression symptoms at some point following their cancer diagnosis.^1-3 These estimates are consistently higher than those of other types of cancer, possibly related to the stigma of the disease and the associated morbidity and mortality that are its hallmarks.^4-8 This potentially life-threatening cancer diagnosis often evokes psychological distress; however, additional stressors contribute to the development of depression, including the effects of chemotherapeutic agents, surgical procedures, radiotherapy, and the consequences of physical symptoms and paraneoplastic syndromes.

In addition to the crippling effects of comorbid depression on patients’ quality of life (QOL), severe and persistent depression among patients with cancer is associated with prolonged hospital stays, worse treatment adherence, physical distress and pain, and increased desire for hastened death.^9-11 During treatment, depression can amplify physical symptoms and interfere with effective coping.^12,13

Depression also is likely a significant factor for the risk of suicide, which is 4 times higher in patients with lung cancer than that of the general population.¹⁴ Most important, as our recent study demonstrated, depression that develops at cancer diagnosis or during cancer treatment may contribute to worse survival. This effect was strongest among patients with early stage disease, in other words, the patients who are most likely to achieve cure.³ This association with early stage disease also has been observed in a strictly veteran population from the northwest U.S.¹⁵

Another key finding of our study was the similar survival among patients who experienced a remission of their depression and those who were never depressed. This finding reinforces the importance of effective depression treatment, which has the potential to reduce depression-related mortality; however, depression treatment was not fully captured and could not be directly compared in our study. Unfortunately, comorbid depression often goes undiagnosed and untreated in cancer patients as they report unmet emotional needs and a desire for psychological support during and after completion of cancer treatment.^16,17

Given the general lack of depression treatment that occurs in patients with cancer, the negative consequences of depression can be sustained well into survivorship—defined clinically as someone who is free of any sign of cancer for 5 years. Cancer survivors frequently report fatigue, mood disturbance, sleep disruption, pain, and cognitive limitations that significantly impact QOL and are associated with disability and increased health care use.¹⁸ These symptoms likely are intertwined with and contribute to the development and persistence of depression. The ramifications of untreated depression on long-term cancer survivor outcomes are not completely understood, as few high-quality studies of depression in cancer survivors exist. However, in a mixed group of patients with cancer, there was a 2-fold risk of mortality in survivors with depression symptoms when these patients were assessed from 1 to 10 years into survivorship.¹⁹ The impact of depression on cancer survivorship is an important aspect of cancer care that deserves significantly more attention from both a research and clinical perspective.

Special Considerations for Veterans

There is a higher prevalence of mental health diagnoses in veterans than that in the general population, and depressive disorders are the most common.^20-22 According to the VA National Registry for Depression, 11% of veterans aged ≥ 65 years have a diagnosis of MDD, a rate more than twice that in the general population of a similar age.²³ However, the actual rate of depression among veterans may be even higher, as studies suggest depression is underdiagnosed in the veteran population.²⁴ In addition to depression, veterans experience other disabling psychological illnesses, such as posttraumatic stress disorder (PTSD) related to deployment and combat duty or combat-related injuries, such as traumatic brain injuries. The negative consequences of PTSD on cancer outcomes are largely unexplored, but PTSD can contribute to increased health care utilization and costs.^25,26 A similar psychological construct, cancer-related posttraumatic stress (PTS), which develops as a result of a cancer diagnosis or treatment, is associated with missed medical appointments and procedures, which could impact survival.²⁷

Depression Screening and Treatment

Given the negative consequences of comorbid mental illness, professional oncology societies have started developing guidelines regarding the assessments and care of patients with cancer who are experiencing symptoms of depression and/or anxiety.^11,28,29 Among these, the American Society of Clinical Oncology (ASCO) has adapted the Pan-Canadian Practice Guideline on Screening, Assessment, and Care of Psychosocial Distress (Depression, Anxiety) in Adults With Cancer.²⁸ Per ASCO, the target audience for these guidelines is health care providers (eg, medical, surgical, and radiation oncologists; psychiatrists; psychologists; primary care providers; nurses; and others involved in the delivery of care for adults with cancer) as well as patients with cancer and their family members and caregivers.²⁸ These guidelines address the optimum screening, assessment, and psychosocial-supportive care interventions for adults with cancer who are identified as experiencing symptoms of depression. Among the most imperative recommendations are periodic assessments across the trajectory of cancer care, including after cure, as well as employing institutional and community resources for depression treatment.

In clinical practice in a VA setting, implementing these guidelines might involve various interventions. First, it is vital for providers to conduct depression screening during periodic health care encounters. Given the high prevalence of depression in patients with lung cancer, we suggest using the 9-item Patient Health Questionnaire (PHQ-9) as an initial screening tool.³⁰ Unlike the abridged 2-item PHQ-2 commonly used in the VA, the PHQ-9 provides an assessment of the full range of depressive symptoms. An elevated PHQ-9 score (≥ 10) is consistent with a major depressive episode and should trigger next steps.³⁰

Once clinically significant depression is identified, initiation of treatment should occur next. The VA is well suited to assist and support non-mental health clinicians—particularly primary care—in treatment initiation and monitoring. This model of partnership is frequently called collaborative care, or integrated care, and it is well positioned to help patients with lung cancer with concomitant depression. In the VA, this model of care is called primary care-mental healthintegration (PC-MHI). One PC-MHI resource is called TIDES (Translating Initiatives for Depression into Effective Solutions), and when a patient is referred, a mental health nurse care manager helps to track the patients’ antidepressant adherence and treatment response while reporting results to primary care clinicians, who are generally responsible for initiating and continuing the antidepressant prescription. For patients preferring nonpharmacologic approaches or for whom an antidepressant may be contraindicated, PC-MHI can provide other assistance. For example, psychologists working in PC-MHI are equipped to provide a brief course of cognitive behavioral therapy sessions, another first-line, evidence-based treatment for clinical depression.

Clinician follow-up to ensure patient adherence, response, and satisfaction, and to adjust treatment as needed is essential. Besides ongoing coordination with PC-MHI services, including mental health clinicians as part of multidisciplinary cancer clinics could offer substantial added value to patients’ comprehensive cancer care. Indeed, the initiation of multicomponent depression care has been shown to improve QOL and role functioning in patients with cancer.³¹ Besides the established benefits on QOL, patients with lung cancer who achieve depression symptom remission also may enjoy a significant survival benefit over patients whose depression symptoms remain untreated during lung cancer treatment as our study suggests.³

Conclusion

Depression is a common comorbid disease among patients with lung cancer with important negative implications for QOL and survival. When it occurs after a cancer diagnosis, depression is expected to impact all phases of a patient’s life through treatment and survivorshi —ultimately affecting long-term survival. Veterans may be at particularly high risk given the increased prevalence of mental illness, including depression and PTSD in this group compared with that of the general population. Early detection and prompt treatment can promote depression remission, prevent relapse, and reduce the eventual emotional and financial burden of the disease. This approach may ultimately diminish the prevalence and persistence of depression symptoms and decrease the associated negative effects of this disease on patients with lung cancer.

The importance of integrated systems of depression treatment for patients with cancer as part of comprehensive cancer care cannot be overstated. Development and implementation of these systems should be a priority of lung cancer clinicians and treatment centers. The integrated system within the VA is well positioned to be a leader in this area, and VA clinicians who care for patients with lung cancer are encouraged to take advantage of available mental health resources. Additional research is urgently needed to explore optimal implementation of depression screening and subsequent treatment delivery to improve cancer patient outcomes in VA and non-VA health care settings.

Acknowledgments
This project was supported in part by the National Cancer Institute of the National Institutes of Health under award K07CA190706 to Dr. Sullivan, a Career Development Award from the Veterans Health Administration Health Service Research and Development (CDA 14-428) to Dr. Teo and the HSR&D Center to Improve Veteran Involvement in Care (CIVIC) (CIN 13-404) at the VA Portland Health Care System.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The VA had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies.

Click here to read the digital edition. 

About Research in Context

In this article, the authors of recent scholarship have been asked to discuss the implications of their research on federal health care providers and specifically the veteran and active-duty service member patient populations. Because the article does not include new research and cannot be blinded, it has undergone an abbreviated peer review process. The original article can be found at Sullivan DR, Forsberg CW, Ganzini L, et al. Longitudinal changes in depression symptoms and survival among patients with lung cancer: a national cohort assessment. J Clin Oncol. 2016;34(33):3984-3991.

Although depression is common among patients with cancer, patients with lung cancer are at particularly high risk. The prevalence of major depressive disorder (MDD) among patients with cancer can be as high as 13%, whereas up to 44% of patients with lung cancer experience depression symptoms at some point following their cancer diagnosis.^1-3 These estimates are consistently higher than those of other types of cancer, possibly related to the stigma of the disease and the associated morbidity and mortality that are its hallmarks.^4-8 This potentially life-threatening cancer diagnosis often evokes psychological distress; however, additional stressors contribute to the development of depression, including the effects of chemotherapeutic agents, surgical procedures, radiotherapy, and the consequences of physical symptoms and paraneoplastic syndromes.

In addition to the crippling effects of comorbid depression on patients’ quality of life (QOL), severe and persistent depression among patients with cancer is associated with prolonged hospital stays, worse treatment adherence, physical distress and pain, and increased desire for hastened death.^9-11 During treatment, depression can amplify physical symptoms and interfere with effective coping.^12,13

Depression also is likely a significant factor for the risk of suicide, which is 4 times higher in patients with lung cancer than that of the general population.¹⁴ Most important, as our recent study demonstrated, depression that develops at cancer diagnosis or during cancer treatment may contribute to worse survival. This effect was strongest among patients with early stage disease, in other words, the patients who are most likely to achieve cure.³ This association with early stage disease also has been observed in a strictly veteran population from the northwest U.S.¹⁵

Another key finding of our study was the similar survival among patients who experienced a remission of their depression and those who were never depressed. This finding reinforces the importance of effective depression treatment, which has the potential to reduce depression-related mortality; however, depression treatment was not fully captured and could not be directly compared in our study. Unfortunately, comorbid depression often goes undiagnosed and untreated in cancer patients as they report unmet emotional needs and a desire for psychological support during and after completion of cancer treatment.^16,17

Given the general lack of depression treatment that occurs in patients with cancer, the negative consequences of depression can be sustained well into survivorship—defined clinically as someone who is free of any sign of cancer for 5 years. Cancer survivors frequently report fatigue, mood disturbance, sleep disruption, pain, and cognitive limitations that significantly impact QOL and are associated with disability and increased health care use.¹⁸ These symptoms likely are intertwined with and contribute to the development and persistence of depression. The ramifications of untreated depression on long-term cancer survivor outcomes are not completely understood, as few high-quality studies of depression in cancer survivors exist. However, in a mixed group of patients with cancer, there was a 2-fold risk of mortality in survivors with depression symptoms when these patients were assessed from 1 to 10 years into survivorship.¹⁹ The impact of depression on cancer survivorship is an important aspect of cancer care that deserves significantly more attention from both a research and clinical perspective.

Special Considerations for Veterans

There is a higher prevalence of mental health diagnoses in veterans than that in the general population, and depressive disorders are the most common.^20-22 According to the VA National Registry for Depression, 11% of veterans aged ≥ 65 years have a diagnosis of MDD, a rate more than twice that in the general population of a similar age.²³ However, the actual rate of depression among veterans may be even higher, as studies suggest depression is underdiagnosed in the veteran population.²⁴ In addition to depression, veterans experience other disabling psychological illnesses, such as posttraumatic stress disorder (PTSD) related to deployment and combat duty or combat-related injuries, such as traumatic brain injuries. The negative consequences of PTSD on cancer outcomes are largely unexplored, but PTSD can contribute to increased health care utilization and costs.^25,26 A similar psychological construct, cancer-related posttraumatic stress (PTS), which develops as a result of a cancer diagnosis or treatment, is associated with missed medical appointments and procedures, which could impact survival.²⁷

Depression Screening and Treatment

Given the negative consequences of comorbid mental illness, professional oncology societies have started developing guidelines regarding the assessments and care of patients with cancer who are experiencing symptoms of depression and/or anxiety.^11,28,29 Among these, the American Society of Clinical Oncology (ASCO) has adapted the Pan-Canadian Practice Guideline on Screening, Assessment, and Care of Psychosocial Distress (Depression, Anxiety) in Adults With Cancer.²⁸ Per ASCO, the target audience for these guidelines is health care providers (eg, medical, surgical, and radiation oncologists; psychiatrists; psychologists; primary care providers; nurses; and others involved in the delivery of care for adults with cancer) as well as patients with cancer and their family members and caregivers.²⁸ These guidelines address the optimum screening, assessment, and psychosocial-supportive care interventions for adults with cancer who are identified as experiencing symptoms of depression. Among the most imperative recommendations are periodic assessments across the trajectory of cancer care, including after cure, as well as employing institutional and community resources for depression treatment.

In clinical practice in a VA setting, implementing these guidelines might involve various interventions. First, it is vital for providers to conduct depression screening during periodic health care encounters. Given the high prevalence of depression in patients with lung cancer, we suggest using the 9-item Patient Health Questionnaire (PHQ-9) as an initial screening tool.³⁰ Unlike the abridged 2-item PHQ-2 commonly used in the VA, the PHQ-9 provides an assessment of the full range of depressive symptoms. An elevated PHQ-9 score (≥ 10) is consistent with a major depressive episode and should trigger next steps.³⁰

Once clinically significant depression is identified, initiation of treatment should occur next. The VA is well suited to assist and support non-mental health clinicians—particularly primary care—in treatment initiation and monitoring. This model of partnership is frequently called collaborative care, or integrated care, and it is well positioned to help patients with lung cancer with concomitant depression. In the VA, this model of care is called primary care-mental healthintegration (PC-MHI). One PC-MHI resource is called TIDES (Translating Initiatives for Depression into Effective Solutions), and when a patient is referred, a mental health nurse care manager helps to track the patients’ antidepressant adherence and treatment response while reporting results to primary care clinicians, who are generally responsible for initiating and continuing the antidepressant prescription. For patients preferring nonpharmacologic approaches or for whom an antidepressant may be contraindicated, PC-MHI can provide other assistance. For example, psychologists working in PC-MHI are equipped to provide a brief course of cognitive behavioral therapy sessions, another first-line, evidence-based treatment for clinical depression.

Clinician follow-up to ensure patient adherence, response, and satisfaction, and to adjust treatment as needed is essential. Besides ongoing coordination with PC-MHI services, including mental health clinicians as part of multidisciplinary cancer clinics could offer substantial added value to patients’ comprehensive cancer care. Indeed, the initiation of multicomponent depression care has been shown to improve QOL and role functioning in patients with cancer.³¹ Besides the established benefits on QOL, patients with lung cancer who achieve depression symptom remission also may enjoy a significant survival benefit over patients whose depression symptoms remain untreated during lung cancer treatment as our study suggests.³

Conclusion

Depression is a common comorbid disease among patients with lung cancer with important negative implications for QOL and survival. When it occurs after a cancer diagnosis, depression is expected to impact all phases of a patient’s life through treatment and survivorshi —ultimately affecting long-term survival. Veterans may be at particularly high risk given the increased prevalence of mental illness, including depression and PTSD in this group compared with that of the general population. Early detection and prompt treatment can promote depression remission, prevent relapse, and reduce the eventual emotional and financial burden of the disease. This approach may ultimately diminish the prevalence and persistence of depression symptoms and decrease the associated negative effects of this disease on patients with lung cancer.

The importance of integrated systems of depression treatment for patients with cancer as part of comprehensive cancer care cannot be overstated. Development and implementation of these systems should be a priority of lung cancer clinicians and treatment centers. The integrated system within the VA is well positioned to be a leader in this area, and VA clinicians who care for patients with lung cancer are encouraged to take advantage of available mental health resources. Additional research is urgently needed to explore optimal implementation of depression screening and subsequent treatment delivery to improve cancer patient outcomes in VA and non-VA health care settings.

Acknowledgments
This project was supported in part by the National Cancer Institute of the National Institutes of Health under award K07CA190706 to Dr. Sullivan, a Career Development Award from the Veterans Health Administration Health Service Research and Development (CDA 14-428) to Dr. Teo and the HSR&D Center to Improve Veteran Involvement in Care (CIVIC) (CIN 13-404) at the VA Portland Health Care System.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The VA had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies.

Click here to read the digital edition. 

Photo from Business Wire

Health Canada has approved emicizumab (Hemlibra®) for use as routine prophylaxis to prevent or reduce bleeding episodes in hemophilia A patients with factor VIII inhibitors.

Emicizumab is a bispecific factor IXa- and factor X-directed antibody. It bridges activated factor IX and factor X to restore the natural function of missing activated factor VIII that is needed for effective blood clotting.

Emicizumab is given as a once-weekly subcutaneous injection.

“Preventing bleeds in patients with hemophilia A can be extremely challenging, usually requiring patients to self-infuse medications multiple times a week, or even daily,” said Jayson Stoffman, MD, of the University of Manitoba in Winnipeg.

“The development of inhibitors adds a significant challenge, with more demanding treatments that are often less effective. Hemlibra offers these patients the chance to effectively reduce the frequency of their bleeds with a once-weekly injection at home. This could significantly improve the quality of life for inhibitor patients, and particularly children and their families.”

Trial results

The Health Canada approval of emicizumab is based on data from a pair of phase 3 trials—HAVEN 1 and HAVEN 2.

Results from HAVEN 1 were published in NEJM and presented at the 26th ISTH Congress in July 2017. Updated results from HAVEN 2 were presented at the 2017 ASH Annual Meeting in December.

HAVEN 1

This study enrolled 109 patients (age 12 and older) with hemophilia A and factor VIII inhibitors who were previously treated with bypassing agents (BPAs) on demand or as prophylaxis.

The patients were randomized to receive emicizumab prophylaxis or no prophylaxis. On-demand treatment of breakthrough bleeds with BPAs was allowed.

There was an 87% reduction in treated bleeds with emicizumab compared to no prophylaxis (P<0.0001). And there was an 80% reduction in all bleeds with emicizumab (P<0.0001).

The proportion of patients with 0 treated bleeds was 62.9% among emicizumab recipients and 5.6% among patients who did not receive prophylaxis.

Adverse events (AEs) occurring in at least 5% of patients treated with emicizumab were local injection site reactions, headache, fatigue, upper respiratory tract infection, and arthralgia.

Two patients experienced thromboembolic events (TEs), and 3 had thrombotic microangiopathy (TMA) while receiving emicizumab prophylaxis and more than 100 µ/kg/day of activated prothrombin complex concentrate, on average, for 24 hours or more before the event. Two of these patients had also received recombinant factor VIIa.

Neither TE required anticoagulation therapy, and 1 patient restarted emicizumab. The cases of TMA observed were transient, and 1 patient restarted emicizumab.

There was 1 death, but it was considered unrelated to emicizumab. The patient had developed TMA but died of rectal hemorrhage.

HAVEN 2

In this single-arm trial, researchers evaluated emicizumab prophylaxis in 60 patients, ages 1 to 17, who had hemophilia A with factor VIII inhibitors.

The efficacy analysis included 57 patients who were younger than 12. The 3 older patients were only included in the safety analysis.

Of the 57 patients, 64.9% had 0 bleeds, 94.7% had 0 treated bleeds, and 98.2% had 0 treated spontaneous bleeds/treated joint bleeds. None of the patients had treated target joint bleeds.

A subset of 23 patients received emicizumab for at least 12 weeks (median treatment duration of 38.1 weeks; range, 12.7 to 41.6 weeks).

Of these 23 patients, 34.8% had 0 bleeds, 87.0% had 0 treated bleeds, and 95.7% had 0 treated spontaneous bleeds/treated joint bleeds.

There were 40 patients who had a total of 201 AEs. The most common of these were viral upper respiratory tract infections (16.7%) and injection site reactions (16.7%).

There were no TEs or TMA events, and none of the patients tested positive for anti-drug antibodies. None of the 7 serious AEs in this trial were considered treatment-related.

Photo from Business Wire

Health Canada has approved emicizumab (Hemlibra®) for use as routine prophylaxis to prevent or reduce bleeding episodes in hemophilia A patients with factor VIII inhibitors.

Emicizumab is a bispecific factor IXa- and factor X-directed antibody. It bridges activated factor IX and factor X to restore the natural function of missing activated factor VIII that is needed for effective blood clotting.

Emicizumab is given as a once-weekly subcutaneous injection.

“Preventing bleeds in patients with hemophilia A can be extremely challenging, usually requiring patients to self-infuse medications multiple times a week, or even daily,” said Jayson Stoffman, MD, of the University of Manitoba in Winnipeg.

“The development of inhibitors adds a significant challenge, with more demanding treatments that are often less effective. Hemlibra offers these patients the chance to effectively reduce the frequency of their bleeds with a once-weekly injection at home. This could significantly improve the quality of life for inhibitor patients, and particularly children and their families.”

Trial results

The Health Canada approval of emicizumab is based on data from a pair of phase 3 trials—HAVEN 1 and HAVEN 2.

Results from HAVEN 1 were published in NEJM and presented at the 26th ISTH Congress in July 2017. Updated results from HAVEN 2 were presented at the 2017 ASH Annual Meeting in December.

HAVEN 1

This study enrolled 109 patients (age 12 and older) with hemophilia A and factor VIII inhibitors who were previously treated with bypassing agents (BPAs) on demand or as prophylaxis.

The patients were randomized to receive emicizumab prophylaxis or no prophylaxis. On-demand treatment of breakthrough bleeds with BPAs was allowed.

There was an 87% reduction in treated bleeds with emicizumab compared to no prophylaxis (P<0.0001). And there was an 80% reduction in all bleeds with emicizumab (P<0.0001).

The proportion of patients with 0 treated bleeds was 62.9% among emicizumab recipients and 5.6% among patients who did not receive prophylaxis.

Adverse events (AEs) occurring in at least 5% of patients treated with emicizumab were local injection site reactions, headache, fatigue, upper respiratory tract infection, and arthralgia.

Two patients experienced thromboembolic events (TEs), and 3 had thrombotic microangiopathy (TMA) while receiving emicizumab prophylaxis and more than 100 µ/kg/day of activated prothrombin complex concentrate, on average, for 24 hours or more before the event. Two of these patients had also received recombinant factor VIIa.

Neither TE required anticoagulation therapy, and 1 patient restarted emicizumab. The cases of TMA observed were transient, and 1 patient restarted emicizumab.

There was 1 death, but it was considered unrelated to emicizumab. The patient had developed TMA but died of rectal hemorrhage.

HAVEN 2

In this single-arm trial, researchers evaluated emicizumab prophylaxis in 60 patients, ages 1 to 17, who had hemophilia A with factor VIII inhibitors.

The efficacy analysis included 57 patients who were younger than 12. The 3 older patients were only included in the safety analysis.

Of the 57 patients, 64.9% had 0 bleeds, 94.7% had 0 treated bleeds, and 98.2% had 0 treated spontaneous bleeds/treated joint bleeds. None of the patients had treated target joint bleeds.

A subset of 23 patients received emicizumab for at least 12 weeks (median treatment duration of 38.1 weeks; range, 12.7 to 41.6 weeks).

Of these 23 patients, 34.8% had 0 bleeds, 87.0% had 0 treated bleeds, and 95.7% had 0 treated spontaneous bleeds/treated joint bleeds.

There were 40 patients who had a total of 201 AEs. The most common of these were viral upper respiratory tract infections (16.7%) and injection site reactions (16.7%).

There were no TEs or TMA events, and none of the patients tested positive for anti-drug antibodies. None of the 7 serious AEs in this trial were considered treatment-related.

Photo from Business Wire

Health Canada has approved emicizumab (Hemlibra®) for use as routine prophylaxis to prevent or reduce bleeding episodes in hemophilia A patients with factor VIII inhibitors.

Emicizumab is a bispecific factor IXa- and factor X-directed antibody. It bridges activated factor IX and factor X to restore the natural function of missing activated factor VIII that is needed for effective blood clotting.

Emicizumab is given as a once-weekly subcutaneous injection.

“Preventing bleeds in patients with hemophilia A can be extremely challenging, usually requiring patients to self-infuse medications multiple times a week, or even daily,” said Jayson Stoffman, MD, of the University of Manitoba in Winnipeg.

“The development of inhibitors adds a significant challenge, with more demanding treatments that are often less effective. Hemlibra offers these patients the chance to effectively reduce the frequency of their bleeds with a once-weekly injection at home. This could significantly improve the quality of life for inhibitor patients, and particularly children and their families.”

Trial results

The Health Canada approval of emicizumab is based on data from a pair of phase 3 trials—HAVEN 1 and HAVEN 2.

Results from HAVEN 1 were published in NEJM and presented at the 26th ISTH Congress in July 2017. Updated results from HAVEN 2 were presented at the 2017 ASH Annual Meeting in December.

HAVEN 1

This study enrolled 109 patients (age 12 and older) with hemophilia A and factor VIII inhibitors who were previously treated with bypassing agents (BPAs) on demand or as prophylaxis.

The patients were randomized to receive emicizumab prophylaxis or no prophylaxis. On-demand treatment of breakthrough bleeds with BPAs was allowed.

There was an 87% reduction in treated bleeds with emicizumab compared to no prophylaxis (P<0.0001). And there was an 80% reduction in all bleeds with emicizumab (P<0.0001).

The proportion of patients with 0 treated bleeds was 62.9% among emicizumab recipients and 5.6% among patients who did not receive prophylaxis.

Adverse events (AEs) occurring in at least 5% of patients treated with emicizumab were local injection site reactions, headache, fatigue, upper respiratory tract infection, and arthralgia.

Two patients experienced thromboembolic events (TEs), and 3 had thrombotic microangiopathy (TMA) while receiving emicizumab prophylaxis and more than 100 µ/kg/day of activated prothrombin complex concentrate, on average, for 24 hours or more before the event. Two of these patients had also received recombinant factor VIIa.

Neither TE required anticoagulation therapy, and 1 patient restarted emicizumab. The cases of TMA observed were transient, and 1 patient restarted emicizumab.

There was 1 death, but it was considered unrelated to emicizumab. The patient had developed TMA but died of rectal hemorrhage.

HAVEN 2

In this single-arm trial, researchers evaluated emicizumab prophylaxis in 60 patients, ages 1 to 17, who had hemophilia A with factor VIII inhibitors.

The efficacy analysis included 57 patients who were younger than 12. The 3 older patients were only included in the safety analysis.

Of the 57 patients, 64.9% had 0 bleeds, 94.7% had 0 treated bleeds, and 98.2% had 0 treated spontaneous bleeds/treated joint bleeds. None of the patients had treated target joint bleeds.

A subset of 23 patients received emicizumab for at least 12 weeks (median treatment duration of 38.1 weeks; range, 12.7 to 41.6 weeks).

Of these 23 patients, 34.8% had 0 bleeds, 87.0% had 0 treated bleeds, and 95.7% had 0 treated spontaneous bleeds/treated joint bleeds.

There were 40 patients who had a total of 201 AEs. The most common of these were viral upper respiratory tract infections (16.7%) and injection site reactions (16.7%).

There were no TEs or TMA events, and none of the patients tested positive for anti-drug antibodies. None of the 7 serious AEs in this trial were considered treatment-related.

Cancer Research Center

Venetoclax might improve the treatment of certain patients with T-cell acute lymphoblastic leukemia (T-ALL), according to preclinical research published in Leukemia.

Researchers found that a ribosomal defect—the R98S mutation in ribosomal protein L10 (RPL10 R98S)—causes overexpression of BCL-2 in T-ALL.

The BCL-2 inhibitor venetoclax induced apoptosis of RPL10 R98S T-ALL cells and inhibited leukemia progression in mouse models of RPL10 R98S T-ALL.

The researchers therefore believe venetoclax could be used, in combination with other drugs, to treat T-ALL patients with RPL10 R98S.

“In the past couple of years, it has become clear that ribosome defects play a role in different types of cancer,” said study author Kim De Keersmaecker, PhD, of KU Leuven in Leuven, Belgium.

“In the case of a ribosome defect, the cells still produce proteins, but the balance between their quantities is slightly off, which leads to cancer.”

Dr De Keersmaecker and her colleagues noted that RPL10 R98S affects 8% of pediatric patients with T-ALL.

With this study, the researchers found that RPL10 R98S mutant cells were more resilient than wild-type (WT) cells. In overgrowth condition, Ba/F3 RPL10 R98S mutant cells “displayed a clear survival benefit” over RPL10 WT cells.

Likewise, RPL10 R98S Jurkat cells exhibited a survival benefit over WT Jurkat cells in overgrowth condition. And RPL10 R98S Jurkat cells were more resistant to treatment with doxorubicin.

Dr De Keersmaecker and her colleagues said the increased survival they observed in RPL10 R98S mutant cells is associated with enhanced BCL-2 expression. So the team decided to test a BCL-2 inhibitor in RPL10 R98S leukemic cells.

In vitro, venetoclax induced slightly more apoptosis in Jurkat RPL10 R98S cells than WT Jurkat cells. In vivo, venetoclax induced apoptosis in RPL10 R98S T-ALL cells but not WT T-ALL cells.

The researchers also found that venetoclax could re-sensitize RPL10 R98S cells to doxorubicin.

Finally, the team injected RPL10 WT and R98S samples from pediatric T-ALL patients into mice and treated the animals with DMSO or venetoclax (50 mg/kg) once a week.

Venetoclax had very little effect on the RPL10 WT mice. Percentages of human CD45 T-ALL cells in the peripheral blood were similar whether mice received DMSO or venetoclax.

However, in the RPL10 R98S mice, those that received DMSO experienced disease progression, while there were no signs of leukemia progression in the peripheral blood of mice that received venetoclax.

The splenomegaly observed in DMSO-treated mice was “almost completely suppressed” in mice that received venetoclax, according to the researchers.

The team also said they observed a 30% to 50% suppression of human CD45 leukemia cell engraftment in the bone marrow and the presence of 30% to 40% mouse CD45 cells in mice treated with venetoclax.

On the other hand, mice treated with DMSO had more than 95% human leukemia infiltration in the bone marrow and no mouse CD45-expressing cells.

Dr De Keersmaecker and her colleagues said these results suggest RPL10 R98S pediatric T-ALL is sensitive to BCL-2 targeted therapies such as venetoclax. However, venetoclax alone would not be sufficient to treat this type of T-ALL.

“Patients with leukemia often get a drug cocktail, while our study only tested the BCL-2 inhibitor,” Dr De Keersmaecker said. “That’s why our follow-up study will focus on a cocktail of this BCL-2 inhibitor and other drugs. For patients with the ribosome defect analyzed in our study, this avenue is definitely worth examining in greater detail.”

Cancer Research Center

Venetoclax might improve the treatment of certain patients with T-cell acute lymphoblastic leukemia (T-ALL), according to preclinical research published in Leukemia.

Researchers found that a ribosomal defect—the R98S mutation in ribosomal protein L10 (RPL10 R98S)—causes overexpression of BCL-2 in T-ALL.

The BCL-2 inhibitor venetoclax induced apoptosis of RPL10 R98S T-ALL cells and inhibited leukemia progression in mouse models of RPL10 R98S T-ALL.

The researchers therefore believe venetoclax could be used, in combination with other drugs, to treat T-ALL patients with RPL10 R98S.

“In the past couple of years, it has become clear that ribosome defects play a role in different types of cancer,” said study author Kim De Keersmaecker, PhD, of KU Leuven in Leuven, Belgium.

“In the case of a ribosome defect, the cells still produce proteins, but the balance between their quantities is slightly off, which leads to cancer.”

Dr De Keersmaecker and her colleagues noted that RPL10 R98S affects 8% of pediatric patients with T-ALL.

With this study, the researchers found that RPL10 R98S mutant cells were more resilient than wild-type (WT) cells. In overgrowth condition, Ba/F3 RPL10 R98S mutant cells “displayed a clear survival benefit” over RPL10 WT cells.

Likewise, RPL10 R98S Jurkat cells exhibited a survival benefit over WT Jurkat cells in overgrowth condition. And RPL10 R98S Jurkat cells were more resistant to treatment with doxorubicin.

Dr De Keersmaecker and her colleagues said the increased survival they observed in RPL10 R98S mutant cells is associated with enhanced BCL-2 expression. So the team decided to test a BCL-2 inhibitor in RPL10 R98S leukemic cells.

In vitro, venetoclax induced slightly more apoptosis in Jurkat RPL10 R98S cells than WT Jurkat cells. In vivo, venetoclax induced apoptosis in RPL10 R98S T-ALL cells but not WT T-ALL cells.

The researchers also found that venetoclax could re-sensitize RPL10 R98S cells to doxorubicin.

Finally, the team injected RPL10 WT and R98S samples from pediatric T-ALL patients into mice and treated the animals with DMSO or venetoclax (50 mg/kg) once a week.

Venetoclax had very little effect on the RPL10 WT mice. Percentages of human CD45 T-ALL cells in the peripheral blood were similar whether mice received DMSO or venetoclax.

However, in the RPL10 R98S mice, those that received DMSO experienced disease progression, while there were no signs of leukemia progression in the peripheral blood of mice that received venetoclax.

The splenomegaly observed in DMSO-treated mice was “almost completely suppressed” in mice that received venetoclax, according to the researchers.

The team also said they observed a 30% to 50% suppression of human CD45 leukemia cell engraftment in the bone marrow and the presence of 30% to 40% mouse CD45 cells in mice treated with venetoclax.

On the other hand, mice treated with DMSO had more than 95% human leukemia infiltration in the bone marrow and no mouse CD45-expressing cells.

Dr De Keersmaecker and her colleagues said these results suggest RPL10 R98S pediatric T-ALL is sensitive to BCL-2 targeted therapies such as venetoclax. However, venetoclax alone would not be sufficient to treat this type of T-ALL.

“Patients with leukemia often get a drug cocktail, while our study only tested the BCL-2 inhibitor,” Dr De Keersmaecker said. “That’s why our follow-up study will focus on a cocktail of this BCL-2 inhibitor and other drugs. For patients with the ribosome defect analyzed in our study, this avenue is definitely worth examining in greater detail.”

Cancer Research Center

Venetoclax might improve the treatment of certain patients with T-cell acute lymphoblastic leukemia (T-ALL), according to preclinical research published in Leukemia.

Researchers found that a ribosomal defect—the R98S mutation in ribosomal protein L10 (RPL10 R98S)—causes overexpression of BCL-2 in T-ALL.

The BCL-2 inhibitor venetoclax induced apoptosis of RPL10 R98S T-ALL cells and inhibited leukemia progression in mouse models of RPL10 R98S T-ALL.

The researchers therefore believe venetoclax could be used, in combination with other drugs, to treat T-ALL patients with RPL10 R98S.

“In the past couple of years, it has become clear that ribosome defects play a role in different types of cancer,” said study author Kim De Keersmaecker, PhD, of KU Leuven in Leuven, Belgium.

“In the case of a ribosome defect, the cells still produce proteins, but the balance between their quantities is slightly off, which leads to cancer.”

Dr De Keersmaecker and her colleagues noted that RPL10 R98S affects 8% of pediatric patients with T-ALL.

With this study, the researchers found that RPL10 R98S mutant cells were more resilient than wild-type (WT) cells. In overgrowth condition, Ba/F3 RPL10 R98S mutant cells “displayed a clear survival benefit” over RPL10 WT cells.

Likewise, RPL10 R98S Jurkat cells exhibited a survival benefit over WT Jurkat cells in overgrowth condition. And RPL10 R98S Jurkat cells were more resistant to treatment with doxorubicin.

Dr De Keersmaecker and her colleagues said the increased survival they observed in RPL10 R98S mutant cells is associated with enhanced BCL-2 expression. So the team decided to test a BCL-2 inhibitor in RPL10 R98S leukemic cells.

In vitro, venetoclax induced slightly more apoptosis in Jurkat RPL10 R98S cells than WT Jurkat cells. In vivo, venetoclax induced apoptosis in RPL10 R98S T-ALL cells but not WT T-ALL cells.

The researchers also found that venetoclax could re-sensitize RPL10 R98S cells to doxorubicin.

Finally, the team injected RPL10 WT and R98S samples from pediatric T-ALL patients into mice and treated the animals with DMSO or venetoclax (50 mg/kg) once a week.

Venetoclax had very little effect on the RPL10 WT mice. Percentages of human CD45 T-ALL cells in the peripheral blood were similar whether mice received DMSO or venetoclax.

However, in the RPL10 R98S mice, those that received DMSO experienced disease progression, while there were no signs of leukemia progression in the peripheral blood of mice that received venetoclax.

The splenomegaly observed in DMSO-treated mice was “almost completely suppressed” in mice that received venetoclax, according to the researchers.

The team also said they observed a 30% to 50% suppression of human CD45 leukemia cell engraftment in the bone marrow and the presence of 30% to 40% mouse CD45 cells in mice treated with venetoclax.

On the other hand, mice treated with DMSO had more than 95% human leukemia infiltration in the bone marrow and no mouse CD45-expressing cells.

Dr De Keersmaecker and her colleagues said these results suggest RPL10 R98S pediatric T-ALL is sensitive to BCL-2 targeted therapies such as venetoclax. However, venetoclax alone would not be sufficient to treat this type of T-ALL.

“Patients with leukemia often get a drug cocktail, while our study only tested the BCL-2 inhibitor,” Dr De Keersmaecker said. “That’s why our follow-up study will focus on a cocktail of this BCL-2 inhibitor and other drugs. For patients with the ribosome defect analyzed in our study, this avenue is definitely worth examining in greater detail.”

Cord blood donation

The US Food and Drug Administration (FDA) has granted fast track designation to dilanubicel (NLA101) for use in patients with high-risk hematologic malignancies receiving an allogeneic cord blood transplant.

Dilanubicel is a universal-donor, ex-vivo-expanded hematopoietic stem and progenitor cell product.

It is intended to induce short-term hematopoiesis, which lasts until a patient’s immune system recovers.

However, dilanubicel may also produce long-term immunologic benefits and could potentially improve survival in transplant recipients, according to Nohla Therapeutics, the company developing the product.

Dilanubicel is manufactured ahead of time, cryopreserved, and intended for immediate off-the-shelf use.

Dilanubicel also has orphan drug designation from the FDA.

About fast track, orphan designations

The FDA’s fast track development program is designed to expedite clinical development and submission of applications for products with the potential to treat serious or life-threatening conditions and address unmet medical needs.

Fast track designation facilitates frequent interactions with the FDA review team, including meetings to discuss the product’s development plan and written communications about issues such as trial design and use of biomarkers.

Products that receive fast track designation may be eligible for accelerated approval and priority review if relevant criteria are met. Such products may also be eligible for rolling review, which allows a developer to submit individual sections of a product’s application for review as they are ready, rather than waiting until all sections are complete.

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US. The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

Trials of dilanubicel

The fast track and orphan designations for dilanubicel were supported by data from a phase 2, single-center study. Results from this study were presented in a poster at the 23rd Congress of European Hematology Association (EHA) in June.

The trial included 15 patients with hematologic malignancies who underwent a cord blood transplant. Conditioning consisted of fludarabine (75 mg/m²), cyclophosphamide (120 mg/kg), and total body irradiation (13.2 Gy).

Patients received unmanipulated cord blood unit(s), followed 4 hours later by dilanubicel infusion. Prophylaxis for graft-vs-host disease (GVHD) was cyclosporine/mycophenolate mofetil.

The researchers compared outcomes in the 15 dilanubicel recipients to outcomes in a concurrent control cohort of 50 patients treated with the same transplant protocol, minus dilanubicel.

The time to neutrophil and platelet recovery were both significantly better in dilanubicel recipients than controls.

At day 100, the cumulative incidence of neutrophil recovery was 100% in dilanubicel recipients and 94% in controls (P=0.005). The median time to neutrophil recovery was 19 days (range, 9-31) and 25 days (range, 14-45), respectively.

The cumulative incidence of platelet recovery was 93% in dilanubicel recipients and 74% in controls (P=0.02). The median time to platelet recovery was 35 days (range, 21-86) and 48 days (range, 24-158), respectively.

At 100 days, there were no cases of grade 3-4 acute GVHD in dilanubicel recipients, but the incidence of grade 3-4 acute GVHD was 29% in the control group.

At 5 years, 27% of dilanubicel recipients had experienced chronic GVHD, compared to 38% of the control group.

There were no cases of transplant related mortality (TRM) in dilanubicel recipients, but the rate of TRM was 16% in the control group.

Two dilanubicel recipients (13%) relapsed post-transplant and subsequently died.

The 5-year disease-free survival rate was 87% in dilanubicel recipients and 66% in the control group. Overall survival rates were the same (87% and 66%, respectively).

Dilanubicel is currently under investigation in a phase 2b trial (NCT01690520) that has enrolled 160 patients with hematologic malignancies. The goal of the trial is to determine whether adding dilanubicel to standard donor cord blood transplant decreases the time to hematopoietic recovery, thereby reducing associated morbidities and mortality.

Another phase 2 trial, called LAUNCH (NCT03301597), is currently enrolling patients who have acute myeloid leukemia and chemotherapy-induced myelosuppression. The goals of this trial are to evaluate dilanubicel’s ability to reduce the rate of grade 3 or higher infections associated with chemotherapy-induced neutropenia and to identify the lowest effective cell dose of dilanubicel.

Cord blood donation

The US Food and Drug Administration (FDA) has granted fast track designation to dilanubicel (NLA101) for use in patients with high-risk hematologic malignancies receiving an allogeneic cord blood transplant.

Dilanubicel is a universal-donor, ex-vivo-expanded hematopoietic stem and progenitor cell product.

It is intended to induce short-term hematopoiesis, which lasts until a patient’s immune system recovers.

However, dilanubicel may also produce long-term immunologic benefits and could potentially improve survival in transplant recipients, according to Nohla Therapeutics, the company developing the product.

Dilanubicel is manufactured ahead of time, cryopreserved, and intended for immediate off-the-shelf use.

Dilanubicel also has orphan drug designation from the FDA.

About fast track, orphan designations

The FDA’s fast track development program is designed to expedite clinical development and submission of applications for products with the potential to treat serious or life-threatening conditions and address unmet medical needs.

Fast track designation facilitates frequent interactions with the FDA review team, including meetings to discuss the product’s development plan and written communications about issues such as trial design and use of biomarkers.

Products that receive fast track designation may be eligible for accelerated approval and priority review if relevant criteria are met. Such products may also be eligible for rolling review, which allows a developer to submit individual sections of a product’s application for review as they are ready, rather than waiting until all sections are complete.

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US. The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

Trials of dilanubicel

The fast track and orphan designations for dilanubicel were supported by data from a phase 2, single-center study. Results from this study were presented in a poster at the 23rd Congress of European Hematology Association (EHA) in June.

The trial included 15 patients with hematologic malignancies who underwent a cord blood transplant. Conditioning consisted of fludarabine (75 mg/m²), cyclophosphamide (120 mg/kg), and total body irradiation (13.2 Gy).

Patients received unmanipulated cord blood unit(s), followed 4 hours later by dilanubicel infusion. Prophylaxis for graft-vs-host disease (GVHD) was cyclosporine/mycophenolate mofetil.

The researchers compared outcomes in the 15 dilanubicel recipients to outcomes in a concurrent control cohort of 50 patients treated with the same transplant protocol, minus dilanubicel.

The time to neutrophil and platelet recovery were both significantly better in dilanubicel recipients than controls.

At day 100, the cumulative incidence of neutrophil recovery was 100% in dilanubicel recipients and 94% in controls (P=0.005). The median time to neutrophil recovery was 19 days (range, 9-31) and 25 days (range, 14-45), respectively.

The cumulative incidence of platelet recovery was 93% in dilanubicel recipients and 74% in controls (P=0.02). The median time to platelet recovery was 35 days (range, 21-86) and 48 days (range, 24-158), respectively.

At 100 days, there were no cases of grade 3-4 acute GVHD in dilanubicel recipients, but the incidence of grade 3-4 acute GVHD was 29% in the control group.

At 5 years, 27% of dilanubicel recipients had experienced chronic GVHD, compared to 38% of the control group.

There were no cases of transplant related mortality (TRM) in dilanubicel recipients, but the rate of TRM was 16% in the control group.

Two dilanubicel recipients (13%) relapsed post-transplant and subsequently died.

The 5-year disease-free survival rate was 87% in dilanubicel recipients and 66% in the control group. Overall survival rates were the same (87% and 66%, respectively).

Dilanubicel is currently under investigation in a phase 2b trial (NCT01690520) that has enrolled 160 patients with hematologic malignancies. The goal of the trial is to determine whether adding dilanubicel to standard donor cord blood transplant decreases the time to hematopoietic recovery, thereby reducing associated morbidities and mortality.

Another phase 2 trial, called LAUNCH (NCT03301597), is currently enrolling patients who have acute myeloid leukemia and chemotherapy-induced myelosuppression. The goals of this trial are to evaluate dilanubicel’s ability to reduce the rate of grade 3 or higher infections associated with chemotherapy-induced neutropenia and to identify the lowest effective cell dose of dilanubicel.

Cord blood donation

The US Food and Drug Administration (FDA) has granted fast track designation to dilanubicel (NLA101) for use in patients with high-risk hematologic malignancies receiving an allogeneic cord blood transplant.

Dilanubicel is a universal-donor, ex-vivo-expanded hematopoietic stem and progenitor cell product.

It is intended to induce short-term hematopoiesis, which lasts until a patient’s immune system recovers.

However, dilanubicel may also produce long-term immunologic benefits and could potentially improve survival in transplant recipients, according to Nohla Therapeutics, the company developing the product.

Dilanubicel is manufactured ahead of time, cryopreserved, and intended for immediate off-the-shelf use.

Dilanubicel also has orphan drug designation from the FDA.

About fast track, orphan designations

The FDA’s fast track development program is designed to expedite clinical development and submission of applications for products with the potential to treat serious or life-threatening conditions and address unmet medical needs.

Fast track designation facilitates frequent interactions with the FDA review team, including meetings to discuss the product’s development plan and written communications about issues such as trial design and use of biomarkers.

Products that receive fast track designation may be eligible for accelerated approval and priority review if relevant criteria are met. Such products may also be eligible for rolling review, which allows a developer to submit individual sections of a product’s application for review as they are ready, rather than waiting until all sections are complete.

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US. The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

Trials of dilanubicel

The fast track and orphan designations for dilanubicel were supported by data from a phase 2, single-center study. Results from this study were presented in a poster at the 23rd Congress of European Hematology Association (EHA) in June.

The trial included 15 patients with hematologic malignancies who underwent a cord blood transplant. Conditioning consisted of fludarabine (75 mg/m²), cyclophosphamide (120 mg/kg), and total body irradiation (13.2 Gy).

Patients received unmanipulated cord blood unit(s), followed 4 hours later by dilanubicel infusion. Prophylaxis for graft-vs-host disease (GVHD) was cyclosporine/mycophenolate mofetil.

The researchers compared outcomes in the 15 dilanubicel recipients to outcomes in a concurrent control cohort of 50 patients treated with the same transplant protocol, minus dilanubicel.

The time to neutrophil and platelet recovery were both significantly better in dilanubicel recipients than controls.

At day 100, the cumulative incidence of neutrophil recovery was 100% in dilanubicel recipients and 94% in controls (P=0.005). The median time to neutrophil recovery was 19 days (range, 9-31) and 25 days (range, 14-45), respectively.

The cumulative incidence of platelet recovery was 93% in dilanubicel recipients and 74% in controls (P=0.02). The median time to platelet recovery was 35 days (range, 21-86) and 48 days (range, 24-158), respectively.

At 100 days, there were no cases of grade 3-4 acute GVHD in dilanubicel recipients, but the incidence of grade 3-4 acute GVHD was 29% in the control group.

At 5 years, 27% of dilanubicel recipients had experienced chronic GVHD, compared to 38% of the control group.

There were no cases of transplant related mortality (TRM) in dilanubicel recipients, but the rate of TRM was 16% in the control group.

Two dilanubicel recipients (13%) relapsed post-transplant and subsequently died.

The 5-year disease-free survival rate was 87% in dilanubicel recipients and 66% in the control group. Overall survival rates were the same (87% and 66%, respectively).

Dilanubicel is currently under investigation in a phase 2b trial (NCT01690520) that has enrolled 160 patients with hematologic malignancies. The goal of the trial is to determine whether adding dilanubicel to standard donor cord blood transplant decreases the time to hematopoietic recovery, thereby reducing associated morbidities and mortality.

Another phase 2 trial, called LAUNCH (NCT03301597), is currently enrolling patients who have acute myeloid leukemia and chemotherapy-induced myelosuppression. The goals of this trial are to evaluate dilanubicel’s ability to reduce the rate of grade 3 or higher infections associated with chemotherapy-induced neutropenia and to identify the lowest effective cell dose of dilanubicel.

There is broad acceptance for the use of guideline-endorsed neuroimaging studies as the standard of care in evaluating early-life epilepsy across U.S pediatric centers, an observational study shows.

Zerbor/Thinkstock

Furthermore, the study authors reported, the use of neuroimaging is supported by their data, which showed that a brain MRI obtained up to 1 year after an early-life epilepsy (ELE) diagnosis provides a high diagnostic yield, regardless of clinical factors – including seizure type or development.

“Neuroimaging, and MRI in particular, frequently identifies an etiology for ELE, enhancing the ability of neurologists to provide a precise diagnosis, offer anticipatory guidance, and consider the full array of available therapies,” wrote Jason Coryell, MD, a child neurologist, and his colleagues Aug. 8 in Pediatrics.

Early childhood epilepsy occurs in 1-2 out of every 1,000 children under age 3, Dr. Coryell and his colleagues said. Consensus guidelines recommend MRI for the evaluation of ELE, but no data evaluate whether it is being used in clinical practice, said Dr. Coryell of the Oregon Health & Science University, Portland, and his colleagues. The research team, therefore, set out to identify the yield and findings of neuroimaging in incident cases of epilepsy in 775 children with newly diagnosed ELE (diagnosed before age 3 years) seen at 17 U.S. pediatric epilepsy centers between 2012 and 2015.

They found that the use of neuroimaging was high, with 725 children (93.5%) having had a neuroimaging study. Of those, 714 had an MRI as recommended in current guidelines (87% with seizure protocols), and 11 had computed tomography or ultrasound only.

According to Dr. Coryell and his colleagues, the high use of MRI in the cohort likely could be attributed to three factors: neuroimaging is recommended in guidelines, the improved accessibility of imaging, and increased physician familiarity with the role of MRI in epilepsy.

Overall, 40% of the children (n = 290) had etiologically relevant abnormalities, a rate that the authors noted was higher than previous estimates. These included an acquired injury in 97 (13.4%), malformations of cortical development in 56 (7.7%), and other diffuse disorders of brain development in 51 (7.0%).

Neuroimaging was abnormal in 61% (160 of 262) of children with abnormal development at diagnosis, compared with 24% (113 of 463) with typical development.

Structural abnormalities also were high and most common in children with focal seizure semiology (40%), spasms (47%), or unclear semiology (42%).

In children without spasms or focal semiology with typical development, 16% (29 of 185 children) had imaging abnormalities. Pathogenic genetic variants were identified in 44% (53 of 121) of children with abnormal neuroimaging in whom genetic testing was performed.

The research team concluded that their data supported the universal adoption of imaging guidelines for ELE, because the yield was substantially high – even in the lowest-risk group.

“In our cohort 1 in 6 children presenting with typical development and without either focal seizures or spasms still had abnormal neuroimaging,” Dr. Coryell and his coauthors wrote. “This supports the continued adherence to guidelines.”

They advised that next steps include standardization of ELE MRI protocol. “Although there has been widespread adoption of epilepsy protocols, these have been geared toward identification of hippocampal abnormalities in older children and adults rather than toward the young, myelinating brain,” the researchers added.

The team noted several limitations. One limitation cited is the study’s identification of patients by using tertiary centers that might provide care for children who are more severely affected than those in the general population.

The Pediatric Epilepsy Research Foundation in Dallas funded the research. Dr. Coryell and his colleagues said they have no financial disclosures. Several of the researchers declared potential conflicts of interest relating to consulting fees.

SOURCE: Coryell J et al. Pediatrics. 2018 Aug 8. doi: 10.1542/peds.2018.0672.

There is broad acceptance for the use of guideline-endorsed neuroimaging studies as the standard of care in evaluating early-life epilepsy across U.S pediatric centers, an observational study shows.

Zerbor/Thinkstock

Furthermore, the study authors reported, the use of neuroimaging is supported by their data, which showed that a brain MRI obtained up to 1 year after an early-life epilepsy (ELE) diagnosis provides a high diagnostic yield, regardless of clinical factors – including seizure type or development.

“Neuroimaging, and MRI in particular, frequently identifies an etiology for ELE, enhancing the ability of neurologists to provide a precise diagnosis, offer anticipatory guidance, and consider the full array of available therapies,” wrote Jason Coryell, MD, a child neurologist, and his colleagues Aug. 8 in Pediatrics.

Early childhood epilepsy occurs in 1-2 out of every 1,000 children under age 3, Dr. Coryell and his colleagues said. Consensus guidelines recommend MRI for the evaluation of ELE, but no data evaluate whether it is being used in clinical practice, said Dr. Coryell of the Oregon Health & Science University, Portland, and his colleagues. The research team, therefore, set out to identify the yield and findings of neuroimaging in incident cases of epilepsy in 775 children with newly diagnosed ELE (diagnosed before age 3 years) seen at 17 U.S. pediatric epilepsy centers between 2012 and 2015.

They found that the use of neuroimaging was high, with 725 children (93.5%) having had a neuroimaging study. Of those, 714 had an MRI as recommended in current guidelines (87% with seizure protocols), and 11 had computed tomography or ultrasound only.

According to Dr. Coryell and his colleagues, the high use of MRI in the cohort likely could be attributed to three factors: neuroimaging is recommended in guidelines, the improved accessibility of imaging, and increased physician familiarity with the role of MRI in epilepsy.

Overall, 40% of the children (n = 290) had etiologically relevant abnormalities, a rate that the authors noted was higher than previous estimates. These included an acquired injury in 97 (13.4%), malformations of cortical development in 56 (7.7%), and other diffuse disorders of brain development in 51 (7.0%).

Neuroimaging was abnormal in 61% (160 of 262) of children with abnormal development at diagnosis, compared with 24% (113 of 463) with typical development.

Structural abnormalities also were high and most common in children with focal seizure semiology (40%), spasms (47%), or unclear semiology (42%).

In children without spasms or focal semiology with typical development, 16% (29 of 185 children) had imaging abnormalities. Pathogenic genetic variants were identified in 44% (53 of 121) of children with abnormal neuroimaging in whom genetic testing was performed.

The research team concluded that their data supported the universal adoption of imaging guidelines for ELE, because the yield was substantially high – even in the lowest-risk group.

“In our cohort 1 in 6 children presenting with typical development and without either focal seizures or spasms still had abnormal neuroimaging,” Dr. Coryell and his coauthors wrote. “This supports the continued adherence to guidelines.”

They advised that next steps include standardization of ELE MRI protocol. “Although there has been widespread adoption of epilepsy protocols, these have been geared toward identification of hippocampal abnormalities in older children and adults rather than toward the young, myelinating brain,” the researchers added.

The team noted several limitations. One limitation cited is the study’s identification of patients by using tertiary centers that might provide care for children who are more severely affected than those in the general population.

The Pediatric Epilepsy Research Foundation in Dallas funded the research. Dr. Coryell and his colleagues said they have no financial disclosures. Several of the researchers declared potential conflicts of interest relating to consulting fees.

SOURCE: Coryell J et al. Pediatrics. 2018 Aug 8. doi: 10.1542/peds.2018.0672.

There is broad acceptance for the use of guideline-endorsed neuroimaging studies as the standard of care in evaluating early-life epilepsy across U.S pediatric centers, an observational study shows.

Zerbor/Thinkstock

Furthermore, the study authors reported, the use of neuroimaging is supported by their data, which showed that a brain MRI obtained up to 1 year after an early-life epilepsy (ELE) diagnosis provides a high diagnostic yield, regardless of clinical factors – including seizure type or development.

“Neuroimaging, and MRI in particular, frequently identifies an etiology for ELE, enhancing the ability of neurologists to provide a precise diagnosis, offer anticipatory guidance, and consider the full array of available therapies,” wrote Jason Coryell, MD, a child neurologist, and his colleagues Aug. 8 in Pediatrics.

Early childhood epilepsy occurs in 1-2 out of every 1,000 children under age 3, Dr. Coryell and his colleagues said. Consensus guidelines recommend MRI for the evaluation of ELE, but no data evaluate whether it is being used in clinical practice, said Dr. Coryell of the Oregon Health & Science University, Portland, and his colleagues. The research team, therefore, set out to identify the yield and findings of neuroimaging in incident cases of epilepsy in 775 children with newly diagnosed ELE (diagnosed before age 3 years) seen at 17 U.S. pediatric epilepsy centers between 2012 and 2015.

They found that the use of neuroimaging was high, with 725 children (93.5%) having had a neuroimaging study. Of those, 714 had an MRI as recommended in current guidelines (87% with seizure protocols), and 11 had computed tomography or ultrasound only.

According to Dr. Coryell and his colleagues, the high use of MRI in the cohort likely could be attributed to three factors: neuroimaging is recommended in guidelines, the improved accessibility of imaging, and increased physician familiarity with the role of MRI in epilepsy.

Overall, 40% of the children (n = 290) had etiologically relevant abnormalities, a rate that the authors noted was higher than previous estimates. These included an acquired injury in 97 (13.4%), malformations of cortical development in 56 (7.7%), and other diffuse disorders of brain development in 51 (7.0%).

Neuroimaging was abnormal in 61% (160 of 262) of children with abnormal development at diagnosis, compared with 24% (113 of 463) with typical development.

Structural abnormalities also were high and most common in children with focal seizure semiology (40%), spasms (47%), or unclear semiology (42%).

In children without spasms or focal semiology with typical development, 16% (29 of 185 children) had imaging abnormalities. Pathogenic genetic variants were identified in 44% (53 of 121) of children with abnormal neuroimaging in whom genetic testing was performed.

The research team concluded that their data supported the universal adoption of imaging guidelines for ELE, because the yield was substantially high – even in the lowest-risk group.

“In our cohort 1 in 6 children presenting with typical development and without either focal seizures or spasms still had abnormal neuroimaging,” Dr. Coryell and his coauthors wrote. “This supports the continued adherence to guidelines.”

They advised that next steps include standardization of ELE MRI protocol. “Although there has been widespread adoption of epilepsy protocols, these have been geared toward identification of hippocampal abnormalities in older children and adults rather than toward the young, myelinating brain,” the researchers added.

The team noted several limitations. One limitation cited is the study’s identification of patients by using tertiary centers that might provide care for children who are more severely affected than those in the general population.

The Pediatric Epilepsy Research Foundation in Dallas funded the research. Dr. Coryell and his colleagues said they have no financial disclosures. Several of the researchers declared potential conflicts of interest relating to consulting fees.

SOURCE: Coryell J et al. Pediatrics. 2018 Aug 8. doi: 10.1542/peds.2018.0672.

CASE Scratching, anxious, and hopeless

Ms. L, age 74, who is paraplegic and uses a wheelchair, presents to our hospital’s emergency department (ED) accompanied by staff from the nursing home where she resides. She reports that she can feel and see bugs crawling all over her skin, biting her, and burrowing into her body. She says that the bugs also stick to her clothes.

Ms. L experiences generalized pruritus with excoriations scattered over her upper and lower extremities and her trunk. She copes with the pruritus by scratching. She reports that the bugs are present throughout the day and are worse at night when she tries to go to bed. Nothing she does provides relief from the infestation. Earlier, at the nursing home, Ms. L had obtained a detergent powder and used it in an attempt to purge the bugs. She now has large swaths of irritated skin, mostly on her lower back and perineal region.

She says the bug infestation became unbearable 3 weeks ago, but she can’t identify any precipitants for her symptoms. Ms. L reports that the impact of the bugs on her daily activity, sleep, and quality of life is enormous. Despite her complaints, neither the nursing home staff nor the ED staff can find any evidence of bugs on Ms. L’s clothes or skin.

Because Ms. L resorted to such drastic measures in her attempt to rid her body of the bugs, she is considered a safety risk and is admitted to the psychiatric unit, although she vehemently denies any intention to harm herself.

On the psychiatric unit, Ms. L states that the infestation began approximately 2 years ago. She began to experience severe worsening of her symptoms a few weeks before presenting to the ED.

During evaluation, Ms. L is alert and oriented to person, place, and situation. She is also quite cooperative but guarded in describing her infestation. There is some degree of suspiciousness and paranoia with regards to her infestation; she is very sensitive to how the clinical staff respond to her condition. She appears worried, and exhibits anxiety, sadness, hopelessness, and tearfulness. Her thought process is goal-directed, but preoccupied by the bugs.

[polldaddy:10064801]

Continue to: The authors' observations

Delusional parasitosis is a rare disorder that is defined by an individual having a fixed, false belief that he or she is being infected or grossly invaded by a living organism. Karl A. Ekbom, a Swedish neurologist, was the first practitioner to definitively describe this affliction in 1938.¹

Primary delusional parasitosis is a disease defined by this single psychotic symptom without other classic symptoms of schizophrenia; this single symptom cannot be attributed to the effects of substance abuse or a medical condition. Many affected patients remain functional in their daily lives; only a minority of patients experience delusions that interfere with usual activity.² Secondary delusional parasitosis is a symptom of another psychiatric or medical disease.

Morgellons disease is characterized by symptoms similar to primary delusional parasitosis, but symptoms of this condition also include the delusional belief that inanimate objects, usually fibers, are in the skin as well as the parasites.³

A population-based study among individuals living in Olmsted County, Minnesota from 1976 to 2010 found that the incidence of delusional infestation was 1.9 cases (95% confidence interval, 1.5 to 2.4) per 100,000 person-years.⁴ In a retrospective study of 147 patients with delusional parasitosis, 33% of these patients described themselves as disabled, 28% were retired, and 26% were employed.⁵ In this study, the mean age of diagnosis was 57, with a female-to-male ratio of 2.89:1.⁵

Continue to: HISTORY Prior psychiatric hospitalization

HISTORY Prior psychiatric hospitalization

Ms. L, who is divorced and retired, lives in a nursing home and has no pets, no exposure to scabies, no recent travel, no allergies, and no difficulty with her hygiene except at the peak of her illness. She denies any alcohol or illicit drug use but reports a 6 pack year history of smoking. She has a son, 2 grandchildren, and 2 great grandchildren who all live in town and see her regularly. She reports no history of arrests or legal problems.

Ms. L has a history of depression and anxiety that culminated in a “nervous breakdown” in 1985 with a brief stay in a psychiatric hospital. She reports that she had seen a therapist for 6 years as part of her treatment following that event. During her hospitalization, she was treated with a tricyclic antidepressant and received electroconvulsive therapy. She denies being suicidal during the incident in 1985 or at any point in time before or since then. She now takes venlafaxine, 75 mg/d, for depression and anxiety.

Ms. L’s paraplegia resulted from her sixth corrective surgery for scoliosis, which occurred 6 years ago. She has had chronic pain since this surgery. Her medical history also includes hypertension, atrial fibrillation, mild neurocognitive changes, and gastroesophageal reflux disease.

EVALUATION Skin examination, blood analysis normal

On admission, Ms. L undergoes a skin examination, which yields no evidence consistent with infestation with Pediculus humanus corporis (body louse) or Sarcoptes scabiei (scabies).⁶ Blood analysis shows no iron deficiency, renal failure, hyperbilirubinemia, or eosinophilia. In the ED, the medical team examines Ms. L and explores other medical and dermatological causes of her condition. Because dermatological causes had been ruled out before Ms. L was admitted to the inpatient psychiatric unit, no dermatology consult is requested.

Continue to: TREATMENT A first-generation antipsychotic

When Ms. L is admitted to the psychiatric unit, she is started on oral perphenazine, 8 mg twice daily, and venlafaxine, 75 mg/d, which she was taking prior to hospital admission. Because she had tolerated venlafaxine with no adverse effects, it seems worthwhile to optimize the dose of this medication rather than start a new medication.

During the week, Ms. L’s perphenazine is titrated up to 24 mg twice daily and venlafaxine is titrated to 150 mg/d. A Montreal Cognitive Assessment (MoCA) is performed within the first 2 days of admission and she scores 16/30, indicating moderate cognitive impairment. On Friday, the attending physician explains that her medications should start to have therapeutic effect. During this time, this clinician engages in cognitive restructuring by providing validation of Ms. L’s suffering, verbal support, and medication compliance counseling. At this time, the treating team also suggests to Ms. L that she should expect the activity and effects of the bugs to dissipate. She is receptive to this suggestion. She also participates in the milieu, including unit activities, but is limited in her ability to engage in group therapy due to the intensity of her illness.

Throughout the weekend, the on-call physician also engages Ms. L and reports minor improvement.

OUTCOME Significant relief

On re-evaluation Monday morning—almost a week after Ms. L had been admitted to the inpatient psychiatric unit—she has achieved significant relief from her delusions. She says that she has no idea where the bugs have gone. Ms. L appears to be a completely different person. She no longer appears guarded. The suspiciousness, paranoia, hopelessness, and negative outlook she previously experienced have significantly diminished. Her MoCA score improves to 25/30, indicating no cognitive impairment (Table). She is discharged after a 7-night stay on the inpatient psychiatric unit.

Continue to: The authors' observations

During one of the clinical multidisciplinary treatment team meetings held for Ms. L, it was initially estimated that it would take at least 2 weeks for the delusional parasitosis to significantly respond to antipsychotic therapy. However, it is our professional opinion that the applied cognitive restructuring, with validation of her suffering, verbal support, and medication adherence counseling, expedited her recovery. This coincided with the aggressive titration of her antipsychotic and antidepressant, although the treatment team’s acknowledgment of Ms. L’s misery appeared to lower her guard and make her more susceptible to the power of cognitive restructuring. The efforts to validate the patient’s feelings and decrease hopelessness by telling her that the medication would make the bugs go away appeared to be the tipping point for her recovery. Patients with primary delusional parasitosis often are guarded and may feel alone in their predicament when they are met with perplexed responses from individuals with whom they discuss their symptoms. Compared with patients with schizophrenia, patients with delusional parasitosis maintain normal cognitive functioning, which may give them the insight to understand how their experience may be perceived as incompatible with reality.⁷ This understanding, coupled with some perceived helplessness, can lead a patient to fear having a severe mental decompensation, which can contribute to a delayed or complicated recovery.

The cognitive process described above might have been responsible for the difference in Ms. L’s MoCA scores because her performance in the initial test was hindered by her constant obsession with the bugs, which made her distracted during the test. By the time she responded to treatment, she gained significant clarity of thought, which enabled her to perform optimally in the test.

The difficulty in treating patients with delusional parasitosis may be further affected by lack of insight, and the fact that they often do not present to a psychiatrist for treatment in a timely manner because their delusion is impregnable and presents them with an alternate reality. These patients are more likely to seek out primary care physicians, dermatologists, infectious disease doctors, and entomologists because of the fervor of their delusion and the intensity of their discomfort. Because of this, a collaboration between these providers would likely lead to improved care and treatment acceptance for patients with delusional parasitosis.

Antipsychotics are the preferred medication for treating delusional parasitosis, and the literature supports their use for this purpose.^6,8 The overall response rate is 60% to 100%.⁶ Previously, in small placebo-­controlled trials, the first-generation antipsychotic (FGA) pimozide was considered first-line treatment for this disease.⁶ However, this antipsychotic is no longer favored because evidence is mounting that other FGAs result in comparable response rates with fewer tolerability issues.^8,9

The bulk of data on the use of antipsychotics for treating delusional parasitosis comes from retrospective case reports and case series.⁶ Multiple antipsychotics have been shown to be effective in treating delusional parasitosis, including both FGAs and second-generation antipsychotics (SGAs).^6,10 Published case reports and series have shown the effectiveness of the FGAs pimozide and haloperidol, among others. One review found that perphenazine, at doses up to 12 mg/d, resulted in partial remission for 2 patients and full remission for 1 patient.⁶

Continue to: The SGAs risperidone, olanzapine, aripiprazole...

The SGAs risperidone, olanzapine, aripiprazole, quetiapine, paliperidone, and ziprasidone have also been used in case reports.^6,8,10,11 Olanzapine and risperidone appear to have the most robust evidence supporting their use. Long-acting injectable antipsychotics, such as long-acting risperidone and paliperidone palmitate, have been used with success.^8,10 A systematic review did not find any evidence to support that any one antipsychotic was superior to another, nor was there a difference in response rate to FGAs or SGAs.⁶ In a case series, Boggild et al¹¹ found that combination therapy with an antidepressant and a low-dose high potency antipsychotic lead to improvements in symptom severity.

When selecting antipsychotic therapy for a patient diagnosed with delusional parasitosis, consider patient-specific factors, such as age, medication history, comorbidities, and the adverse-effect profile of the medication(s). These medications should be started at a low dose and titrated based on efficacy and safety. The optimal duration of therapy varies by patient. Patients should continually be assessed for possible treatment discontinuation, although if therapy is tapered off, patients need to be closely monitored for possible relapse or recurrence of symptoms.

Ms. L received perphenazine titrated up to 24 mg/d for the treatment of delusional parasitosis. The maximum dose used for Ms. L was higher than those used in previous reports, although she appeared to tolerate the medication well and respond rapidly. Her symptoms showed improvement within 1 week. Importantly, in published case reports, patients have been resistant to the use of psychotropic medications without other treatment modalities (eg, psychotherapy, various behavioral approaches). We conclude that Ms. L’s response was attributable to the use of the combination of psychotherapeutic techniques and the effectiveness of perphenazine and venlafaxine.

Bottom Line

Managing patients with primary delusional parasitosis can be challenging due to the fixed nature of the delusion. A combination of antipsychotics and psychotherapeutic techniques can benefit some patients. The optimal duration of treatment varies by patient.

Related Resource

• Trenton A, Pansare N, Tobia A, et al. Delusional parasitosis on the psychiatric consultation service-a longitudinal perspective: case study. BJPsych Open. 2017;3(3):154-158. 

Drug Brand Names

Aripiprazole • Abilify
Haloperidol • Haldol
Olanzapine • Zyprexa
Paliperidone • Invega
Paliperidone palmitate • Invega Sustenna
Perphenazine • Trilafon
Pimozide • Orap
Quetiapine • Seroquel
Risperidone • Risperdal
Venlafaxine • Effexor  
Ziprasidone • Geodon

CASE Scratching, anxious, and hopeless

Ms. L, age 74, who is paraplegic and uses a wheelchair, presents to our hospital’s emergency department (ED) accompanied by staff from the nursing home where she resides. She reports that she can feel and see bugs crawling all over her skin, biting her, and burrowing into her body. She says that the bugs also stick to her clothes.

Ms. L experiences generalized pruritus with excoriations scattered over her upper and lower extremities and her trunk. She copes with the pruritus by scratching. She reports that the bugs are present throughout the day and are worse at night when she tries to go to bed. Nothing she does provides relief from the infestation. Earlier, at the nursing home, Ms. L had obtained a detergent powder and used it in an attempt to purge the bugs. She now has large swaths of irritated skin, mostly on her lower back and perineal region.

She says the bug infestation became unbearable 3 weeks ago, but she can’t identify any precipitants for her symptoms. Ms. L reports that the impact of the bugs on her daily activity, sleep, and quality of life is enormous. Despite her complaints, neither the nursing home staff nor the ED staff can find any evidence of bugs on Ms. L’s clothes or skin.

Because Ms. L resorted to such drastic measures in her attempt to rid her body of the bugs, she is considered a safety risk and is admitted to the psychiatric unit, although she vehemently denies any intention to harm herself.

On the psychiatric unit, Ms. L states that the infestation began approximately 2 years ago. She began to experience severe worsening of her symptoms a few weeks before presenting to the ED.

During evaluation, Ms. L is alert and oriented to person, place, and situation. She is also quite cooperative but guarded in describing her infestation. There is some degree of suspiciousness and paranoia with regards to her infestation; she is very sensitive to how the clinical staff respond to her condition. She appears worried, and exhibits anxiety, sadness, hopelessness, and tearfulness. Her thought process is goal-directed, but preoccupied by the bugs.

[polldaddy:10064801]

Continue to: The authors' observations

Delusional parasitosis is a rare disorder that is defined by an individual having a fixed, false belief that he or she is being infected or grossly invaded by a living organism. Karl A. Ekbom, a Swedish neurologist, was the first practitioner to definitively describe this affliction in 1938.¹

Primary delusional parasitosis is a disease defined by this single psychotic symptom without other classic symptoms of schizophrenia; this single symptom cannot be attributed to the effects of substance abuse or a medical condition. Many affected patients remain functional in their daily lives; only a minority of patients experience delusions that interfere with usual activity.² Secondary delusional parasitosis is a symptom of another psychiatric or medical disease.

Morgellons disease is characterized by symptoms similar to primary delusional parasitosis, but symptoms of this condition also include the delusional belief that inanimate objects, usually fibers, are in the skin as well as the parasites.³

A population-based study among individuals living in Olmsted County, Minnesota from 1976 to 2010 found that the incidence of delusional infestation was 1.9 cases (95% confidence interval, 1.5 to 2.4) per 100,000 person-years.⁴ In a retrospective study of 147 patients with delusional parasitosis, 33% of these patients described themselves as disabled, 28% were retired, and 26% were employed.⁵ In this study, the mean age of diagnosis was 57, with a female-to-male ratio of 2.89:1.⁵

Continue to: HISTORY Prior psychiatric hospitalization

HISTORY Prior psychiatric hospitalization

Ms. L, who is divorced and retired, lives in a nursing home and has no pets, no exposure to scabies, no recent travel, no allergies, and no difficulty with her hygiene except at the peak of her illness. She denies any alcohol or illicit drug use but reports a 6 pack year history of smoking. She has a son, 2 grandchildren, and 2 great grandchildren who all live in town and see her regularly. She reports no history of arrests or legal problems.

Ms. L has a history of depression and anxiety that culminated in a “nervous breakdown” in 1985 with a brief stay in a psychiatric hospital. She reports that she had seen a therapist for 6 years as part of her treatment following that event. During her hospitalization, she was treated with a tricyclic antidepressant and received electroconvulsive therapy. She denies being suicidal during the incident in 1985 or at any point in time before or since then. She now takes venlafaxine, 75 mg/d, for depression and anxiety.

Ms. L’s paraplegia resulted from her sixth corrective surgery for scoliosis, which occurred 6 years ago. She has had chronic pain since this surgery. Her medical history also includes hypertension, atrial fibrillation, mild neurocognitive changes, and gastroesophageal reflux disease.

EVALUATION Skin examination, blood analysis normal

On admission, Ms. L undergoes a skin examination, which yields no evidence consistent with infestation with Pediculus humanus corporis (body louse) or Sarcoptes scabiei (scabies).⁶ Blood analysis shows no iron deficiency, renal failure, hyperbilirubinemia, or eosinophilia. In the ED, the medical team examines Ms. L and explores other medical and dermatological causes of her condition. Because dermatological causes had been ruled out before Ms. L was admitted to the inpatient psychiatric unit, no dermatology consult is requested.

Continue to: TREATMENT A first-generation antipsychotic

When Ms. L is admitted to the psychiatric unit, she is started on oral perphenazine, 8 mg twice daily, and venlafaxine, 75 mg/d, which she was taking prior to hospital admission. Because she had tolerated venlafaxine with no adverse effects, it seems worthwhile to optimize the dose of this medication rather than start a new medication.

During the week, Ms. L’s perphenazine is titrated up to 24 mg twice daily and venlafaxine is titrated to 150 mg/d. A Montreal Cognitive Assessment (MoCA) is performed within the first 2 days of admission and she scores 16/30, indicating moderate cognitive impairment. On Friday, the attending physician explains that her medications should start to have therapeutic effect. During this time, this clinician engages in cognitive restructuring by providing validation of Ms. L’s suffering, verbal support, and medication compliance counseling. At this time, the treating team also suggests to Ms. L that she should expect the activity and effects of the bugs to dissipate. She is receptive to this suggestion. She also participates in the milieu, including unit activities, but is limited in her ability to engage in group therapy due to the intensity of her illness.

Throughout the weekend, the on-call physician also engages Ms. L and reports minor improvement.

OUTCOME Significant relief

On re-evaluation Monday morning—almost a week after Ms. L had been admitted to the inpatient psychiatric unit—she has achieved significant relief from her delusions. She says that she has no idea where the bugs have gone. Ms. L appears to be a completely different person. She no longer appears guarded. The suspiciousness, paranoia, hopelessness, and negative outlook she previously experienced have significantly diminished. Her MoCA score improves to 25/30, indicating no cognitive impairment (Table). She is discharged after a 7-night stay on the inpatient psychiatric unit.

Continue to: The authors' observations

During one of the clinical multidisciplinary treatment team meetings held for Ms. L, it was initially estimated that it would take at least 2 weeks for the delusional parasitosis to significantly respond to antipsychotic therapy. However, it is our professional opinion that the applied cognitive restructuring, with validation of her suffering, verbal support, and medication adherence counseling, expedited her recovery. This coincided with the aggressive titration of her antipsychotic and antidepressant, although the treatment team’s acknowledgment of Ms. L’s misery appeared to lower her guard and make her more susceptible to the power of cognitive restructuring. The efforts to validate the patient’s feelings and decrease hopelessness by telling her that the medication would make the bugs go away appeared to be the tipping point for her recovery. Patients with primary delusional parasitosis often are guarded and may feel alone in their predicament when they are met with perplexed responses from individuals with whom they discuss their symptoms. Compared with patients with schizophrenia, patients with delusional parasitosis maintain normal cognitive functioning, which may give them the insight to understand how their experience may be perceived as incompatible with reality.⁷ This understanding, coupled with some perceived helplessness, can lead a patient to fear having a severe mental decompensation, which can contribute to a delayed or complicated recovery.

The cognitive process described above might have been responsible for the difference in Ms. L’s MoCA scores because her performance in the initial test was hindered by her constant obsession with the bugs, which made her distracted during the test. By the time she responded to treatment, she gained significant clarity of thought, which enabled her to perform optimally in the test.

The difficulty in treating patients with delusional parasitosis may be further affected by lack of insight, and the fact that they often do not present to a psychiatrist for treatment in a timely manner because their delusion is impregnable and presents them with an alternate reality. These patients are more likely to seek out primary care physicians, dermatologists, infectious disease doctors, and entomologists because of the fervor of their delusion and the intensity of their discomfort. Because of this, a collaboration between these providers would likely lead to improved care and treatment acceptance for patients with delusional parasitosis.

Antipsychotics are the preferred medication for treating delusional parasitosis, and the literature supports their use for this purpose.^6,8 The overall response rate is 60% to 100%.⁶ Previously, in small placebo-­controlled trials, the first-generation antipsychotic (FGA) pimozide was considered first-line treatment for this disease.⁶ However, this antipsychotic is no longer favored because evidence is mounting that other FGAs result in comparable response rates with fewer tolerability issues.^8,9

The bulk of data on the use of antipsychotics for treating delusional parasitosis comes from retrospective case reports and case series.⁶ Multiple antipsychotics have been shown to be effective in treating delusional parasitosis, including both FGAs and second-generation antipsychotics (SGAs).^6,10 Published case reports and series have shown the effectiveness of the FGAs pimozide and haloperidol, among others. One review found that perphenazine, at doses up to 12 mg/d, resulted in partial remission for 2 patients and full remission for 1 patient.⁶

Continue to: The SGAs risperidone, olanzapine, aripiprazole...

The SGAs risperidone, olanzapine, aripiprazole, quetiapine, paliperidone, and ziprasidone have also been used in case reports.^6,8,10,11 Olanzapine and risperidone appear to have the most robust evidence supporting their use. Long-acting injectable antipsychotics, such as long-acting risperidone and paliperidone palmitate, have been used with success.^8,10 A systematic review did not find any evidence to support that any one antipsychotic was superior to another, nor was there a difference in response rate to FGAs or SGAs.⁶ In a case series, Boggild et al¹¹ found that combination therapy with an antidepressant and a low-dose high potency antipsychotic lead to improvements in symptom severity.

When selecting antipsychotic therapy for a patient diagnosed with delusional parasitosis, consider patient-specific factors, such as age, medication history, comorbidities, and the adverse-effect profile of the medication(s). These medications should be started at a low dose and titrated based on efficacy and safety. The optimal duration of therapy varies by patient. Patients should continually be assessed for possible treatment discontinuation, although if therapy is tapered off, patients need to be closely monitored for possible relapse or recurrence of symptoms.

Ms. L received perphenazine titrated up to 24 mg/d for the treatment of delusional parasitosis. The maximum dose used for Ms. L was higher than those used in previous reports, although she appeared to tolerate the medication well and respond rapidly. Her symptoms showed improvement within 1 week. Importantly, in published case reports, patients have been resistant to the use of psychotropic medications without other treatment modalities (eg, psychotherapy, various behavioral approaches). We conclude that Ms. L’s response was attributable to the use of the combination of psychotherapeutic techniques and the effectiveness of perphenazine and venlafaxine.

Bottom Line

Managing patients with primary delusional parasitosis can be challenging due to the fixed nature of the delusion. A combination of antipsychotics and psychotherapeutic techniques can benefit some patients. The optimal duration of treatment varies by patient.

Related Resource

• Trenton A, Pansare N, Tobia A, et al. Delusional parasitosis on the psychiatric consultation service-a longitudinal perspective: case study. BJPsych Open. 2017;3(3):154-158. 

Drug Brand Names

Aripiprazole • Abilify
Haloperidol • Haldol
Olanzapine • Zyprexa
Paliperidone • Invega
Paliperidone palmitate • Invega Sustenna
Perphenazine • Trilafon
Pimozide • Orap
Quetiapine • Seroquel
Risperidone • Risperdal
Venlafaxine • Effexor  
Ziprasidone • Geodon

CASE Scratching, anxious, and hopeless

Ms. L, age 74, who is paraplegic and uses a wheelchair, presents to our hospital’s emergency department (ED) accompanied by staff from the nursing home where she resides. She reports that she can feel and see bugs crawling all over her skin, biting her, and burrowing into her body. She says that the bugs also stick to her clothes.

Ms. L experiences generalized pruritus with excoriations scattered over her upper and lower extremities and her trunk. She copes with the pruritus by scratching. She reports that the bugs are present throughout the day and are worse at night when she tries to go to bed. Nothing she does provides relief from the infestation. Earlier, at the nursing home, Ms. L had obtained a detergent powder and used it in an attempt to purge the bugs. She now has large swaths of irritated skin, mostly on her lower back and perineal region.

She says the bug infestation became unbearable 3 weeks ago, but she can’t identify any precipitants for her symptoms. Ms. L reports that the impact of the bugs on her daily activity, sleep, and quality of life is enormous. Despite her complaints, neither the nursing home staff nor the ED staff can find any evidence of bugs on Ms. L’s clothes or skin.

Because Ms. L resorted to such drastic measures in her attempt to rid her body of the bugs, she is considered a safety risk and is admitted to the psychiatric unit, although she vehemently denies any intention to harm herself.

On the psychiatric unit, Ms. L states that the infestation began approximately 2 years ago. She began to experience severe worsening of her symptoms a few weeks before presenting to the ED.

During evaluation, Ms. L is alert and oriented to person, place, and situation. She is also quite cooperative but guarded in describing her infestation. There is some degree of suspiciousness and paranoia with regards to her infestation; she is very sensitive to how the clinical staff respond to her condition. She appears worried, and exhibits anxiety, sadness, hopelessness, and tearfulness. Her thought process is goal-directed, but preoccupied by the bugs.

[polldaddy:10064801]

Continue to: The authors' observations

Delusional parasitosis is a rare disorder that is defined by an individual having a fixed, false belief that he or she is being infected or grossly invaded by a living organism. Karl A. Ekbom, a Swedish neurologist, was the first practitioner to definitively describe this affliction in 1938.¹

Primary delusional parasitosis is a disease defined by this single psychotic symptom without other classic symptoms of schizophrenia; this single symptom cannot be attributed to the effects of substance abuse or a medical condition. Many affected patients remain functional in their daily lives; only a minority of patients experience delusions that interfere with usual activity.² Secondary delusional parasitosis is a symptom of another psychiatric or medical disease.

Morgellons disease is characterized by symptoms similar to primary delusional parasitosis, but symptoms of this condition also include the delusional belief that inanimate objects, usually fibers, are in the skin as well as the parasites.³

A population-based study among individuals living in Olmsted County, Minnesota from 1976 to 2010 found that the incidence of delusional infestation was 1.9 cases (95% confidence interval, 1.5 to 2.4) per 100,000 person-years.⁴ In a retrospective study of 147 patients with delusional parasitosis, 33% of these patients described themselves as disabled, 28% were retired, and 26% were employed.⁵ In this study, the mean age of diagnosis was 57, with a female-to-male ratio of 2.89:1.⁵

Continue to: HISTORY Prior psychiatric hospitalization

HISTORY Prior psychiatric hospitalization

Ms. L, who is divorced and retired, lives in a nursing home and has no pets, no exposure to scabies, no recent travel, no allergies, and no difficulty with her hygiene except at the peak of her illness. She denies any alcohol or illicit drug use but reports a 6 pack year history of smoking. She has a son, 2 grandchildren, and 2 great grandchildren who all live in town and see her regularly. She reports no history of arrests or legal problems.

Ms. L has a history of depression and anxiety that culminated in a “nervous breakdown” in 1985 with a brief stay in a psychiatric hospital. She reports that she had seen a therapist for 6 years as part of her treatment following that event. During her hospitalization, she was treated with a tricyclic antidepressant and received electroconvulsive therapy. She denies being suicidal during the incident in 1985 or at any point in time before or since then. She now takes venlafaxine, 75 mg/d, for depression and anxiety.

Ms. L’s paraplegia resulted from her sixth corrective surgery for scoliosis, which occurred 6 years ago. She has had chronic pain since this surgery. Her medical history also includes hypertension, atrial fibrillation, mild neurocognitive changes, and gastroesophageal reflux disease.

EVALUATION Skin examination, blood analysis normal

On admission, Ms. L undergoes a skin examination, which yields no evidence consistent with infestation with Pediculus humanus corporis (body louse) or Sarcoptes scabiei (scabies).⁶ Blood analysis shows no iron deficiency, renal failure, hyperbilirubinemia, or eosinophilia. In the ED, the medical team examines Ms. L and explores other medical and dermatological causes of her condition. Because dermatological causes had been ruled out before Ms. L was admitted to the inpatient psychiatric unit, no dermatology consult is requested.

Continue to: TREATMENT A first-generation antipsychotic

When Ms. L is admitted to the psychiatric unit, she is started on oral perphenazine, 8 mg twice daily, and venlafaxine, 75 mg/d, which she was taking prior to hospital admission. Because she had tolerated venlafaxine with no adverse effects, it seems worthwhile to optimize the dose of this medication rather than start a new medication.

During the week, Ms. L’s perphenazine is titrated up to 24 mg twice daily and venlafaxine is titrated to 150 mg/d. A Montreal Cognitive Assessment (MoCA) is performed within the first 2 days of admission and she scores 16/30, indicating moderate cognitive impairment. On Friday, the attending physician explains that her medications should start to have therapeutic effect. During this time, this clinician engages in cognitive restructuring by providing validation of Ms. L’s suffering, verbal support, and medication compliance counseling. At this time, the treating team also suggests to Ms. L that she should expect the activity and effects of the bugs to dissipate. She is receptive to this suggestion. She also participates in the milieu, including unit activities, but is limited in her ability to engage in group therapy due to the intensity of her illness.

Throughout the weekend, the on-call physician also engages Ms. L and reports minor improvement.

OUTCOME Significant relief

On re-evaluation Monday morning—almost a week after Ms. L had been admitted to the inpatient psychiatric unit—she has achieved significant relief from her delusions. She says that she has no idea where the bugs have gone. Ms. L appears to be a completely different person. She no longer appears guarded. The suspiciousness, paranoia, hopelessness, and negative outlook she previously experienced have significantly diminished. Her MoCA score improves to 25/30, indicating no cognitive impairment (Table). She is discharged after a 7-night stay on the inpatient psychiatric unit.

Continue to: The authors' observations

During one of the clinical multidisciplinary treatment team meetings held for Ms. L, it was initially estimated that it would take at least 2 weeks for the delusional parasitosis to significantly respond to antipsychotic therapy. However, it is our professional opinion that the applied cognitive restructuring, with validation of her suffering, verbal support, and medication adherence counseling, expedited her recovery. This coincided with the aggressive titration of her antipsychotic and antidepressant, although the treatment team’s acknowledgment of Ms. L’s misery appeared to lower her guard and make her more susceptible to the power of cognitive restructuring. The efforts to validate the patient’s feelings and decrease hopelessness by telling her that the medication would make the bugs go away appeared to be the tipping point for her recovery. Patients with primary delusional parasitosis often are guarded and may feel alone in their predicament when they are met with perplexed responses from individuals with whom they discuss their symptoms. Compared with patients with schizophrenia, patients with delusional parasitosis maintain normal cognitive functioning, which may give them the insight to understand how their experience may be perceived as incompatible with reality.⁷ This understanding, coupled with some perceived helplessness, can lead a patient to fear having a severe mental decompensation, which can contribute to a delayed or complicated recovery.

The cognitive process described above might have been responsible for the difference in Ms. L’s MoCA scores because her performance in the initial test was hindered by her constant obsession with the bugs, which made her distracted during the test. By the time she responded to treatment, she gained significant clarity of thought, which enabled her to perform optimally in the test.

The difficulty in treating patients with delusional parasitosis may be further affected by lack of insight, and the fact that they often do not present to a psychiatrist for treatment in a timely manner because their delusion is impregnable and presents them with an alternate reality. These patients are more likely to seek out primary care physicians, dermatologists, infectious disease doctors, and entomologists because of the fervor of their delusion and the intensity of their discomfort. Because of this, a collaboration between these providers would likely lead to improved care and treatment acceptance for patients with delusional parasitosis.

Antipsychotics are the preferred medication for treating delusional parasitosis, and the literature supports their use for this purpose.^6,8 The overall response rate is 60% to 100%.⁶ Previously, in small placebo-­controlled trials, the first-generation antipsychotic (FGA) pimozide was considered first-line treatment for this disease.⁶ However, this antipsychotic is no longer favored because evidence is mounting that other FGAs result in comparable response rates with fewer tolerability issues.^8,9

The bulk of data on the use of antipsychotics for treating delusional parasitosis comes from retrospective case reports and case series.⁶ Multiple antipsychotics have been shown to be effective in treating delusional parasitosis, including both FGAs and second-generation antipsychotics (SGAs).^6,10 Published case reports and series have shown the effectiveness of the FGAs pimozide and haloperidol, among others. One review found that perphenazine, at doses up to 12 mg/d, resulted in partial remission for 2 patients and full remission for 1 patient.⁶

Continue to: The SGAs risperidone, olanzapine, aripiprazole...

The SGAs risperidone, olanzapine, aripiprazole, quetiapine, paliperidone, and ziprasidone have also been used in case reports.^6,8,10,11 Olanzapine and risperidone appear to have the most robust evidence supporting their use. Long-acting injectable antipsychotics, such as long-acting risperidone and paliperidone palmitate, have been used with success.^8,10 A systematic review did not find any evidence to support that any one antipsychotic was superior to another, nor was there a difference in response rate to FGAs or SGAs.⁶ In a case series, Boggild et al¹¹ found that combination therapy with an antidepressant and a low-dose high potency antipsychotic lead to improvements in symptom severity.

When selecting antipsychotic therapy for a patient diagnosed with delusional parasitosis, consider patient-specific factors, such as age, medication history, comorbidities, and the adverse-effect profile of the medication(s). These medications should be started at a low dose and titrated based on efficacy and safety. The optimal duration of therapy varies by patient. Patients should continually be assessed for possible treatment discontinuation, although if therapy is tapered off, patients need to be closely monitored for possible relapse or recurrence of symptoms.

Ms. L received perphenazine titrated up to 24 mg/d for the treatment of delusional parasitosis. The maximum dose used for Ms. L was higher than those used in previous reports, although she appeared to tolerate the medication well and respond rapidly. Her symptoms showed improvement within 1 week. Importantly, in published case reports, patients have been resistant to the use of psychotropic medications without other treatment modalities (eg, psychotherapy, various behavioral approaches). We conclude that Ms. L’s response was attributable to the use of the combination of psychotherapeutic techniques and the effectiveness of perphenazine and venlafaxine.

Bottom Line

Managing patients with primary delusional parasitosis can be challenging due to the fixed nature of the delusion. A combination of antipsychotics and psychotherapeutic techniques can benefit some patients. The optimal duration of treatment varies by patient.

Related Resource

• Trenton A, Pansare N, Tobia A, et al. Delusional parasitosis on the psychiatric consultation service-a longitudinal perspective: case study. BJPsych Open. 2017;3(3):154-158. 

Drug Brand Names

Aripiprazole • Abilify
Haloperidol • Haldol
Olanzapine • Zyprexa
Paliperidone • Invega
Paliperidone palmitate • Invega Sustenna
Perphenazine • Trilafon
Pimozide • Orap
Quetiapine • Seroquel
Risperidone • Risperdal
Venlafaxine • Effexor  
Ziprasidone • Geodon

ANSWER

The correct interpretation includes marked sinus bradycardia with sinus arrhythmia, biatrial enlargement, and an RSR’ pattern in lead V₁ suggestive of right ventricular conduction delay.

A heart rate below 60 beats/min is considered sinus bradycardia; below 50 beats/min, it may be called marked sinus bradycardia. Sinus arrhythmia is identified by comparing the RR intervals between the third/fourth and fourth/fifth beats on the rhythm strips with the others. This particular variation is most likely respiratory.

Biatrial enlargement is characterized by P waves ≥ 2.5 mm in lead II (right atrial enlargement), P waves > 120 ms in width in lead II, and a biphasic P wave in lead V₁ (> 40 ms wide, 1 mm deep). The criteria aren’t crystal clear in this example, but given the large P wave in leads II and aVF and the biphasic P waves in lead V₁, the finding is inferred.

Finally, the RSR’ pattern in V₁ suggests right ventricular conduction delay but does not meet the criteria (QRS duration > 120 ms) for a right bundle branch block.

ANSWER

The correct interpretation includes marked sinus bradycardia with sinus arrhythmia, biatrial enlargement, and an RSR’ pattern in lead V₁ suggestive of right ventricular conduction delay.

A heart rate below 60 beats/min is considered sinus bradycardia; below 50 beats/min, it may be called marked sinus bradycardia. Sinus arrhythmia is identified by comparing the RR intervals between the third/fourth and fourth/fifth beats on the rhythm strips with the others. This particular variation is most likely respiratory.

Biatrial enlargement is characterized by P waves ≥ 2.5 mm in lead II (right atrial enlargement), P waves > 120 ms in width in lead II, and a biphasic P wave in lead V₁ (> 40 ms wide, 1 mm deep). The criteria aren’t crystal clear in this example, but given the large P wave in leads II and aVF and the biphasic P waves in lead V₁, the finding is inferred.

Finally, the RSR’ pattern in V₁ suggests right ventricular conduction delay but does not meet the criteria (QRS duration > 120 ms) for a right bundle branch block.

ANSWER

The correct interpretation includes marked sinus bradycardia with sinus arrhythmia, biatrial enlargement, and an RSR’ pattern in lead V₁ suggestive of right ventricular conduction delay.

A heart rate below 60 beats/min is considered sinus bradycardia; below 50 beats/min, it may be called marked sinus bradycardia. Sinus arrhythmia is identified by comparing the RR intervals between the third/fourth and fourth/fifth beats on the rhythm strips with the others. This particular variation is most likely respiratory.

Biatrial enlargement is characterized by P waves ≥ 2.5 mm in lead II (right atrial enlargement), P waves > 120 ms in width in lead II, and a biphasic P wave in lead V₁ (> 40 ms wide, 1 mm deep). The criteria aren’t crystal clear in this example, but given the large P wave in leads II and aVF and the biphasic P waves in lead V₁, the finding is inferred.

Finally, the RSR’ pattern in V₁ suggests right ventricular conduction delay but does not meet the criteria (QRS duration > 120 ms) for a right bundle branch block.