The US Food and Drug Administration uses the term boxed warning to highlight potentially dangerous situations associated with prescription drugs. A boxed warning is used when “[T]here is an adverse reaction so serious in proportion to the potential benefit from the drug (e.g., a fatal, life-threatening or permanently disabling adverse reaction) that it is essential that it be considered in assessing the risks and benefits of using the drug.”¹ However, drugs are not the only potential cause of severe adverse outcomes in patients with psoriasis. Untreated psoriasis also is a well-established cause of serious morbidity and mortality. What are the risks of inadequate psoriasis treatment?

Psoriasis is associated with an increased risk for cardiovascular disease.^2-4 Patients with psoriasis also have a higher prevalence of classic cardiovascular risk factors including smoking, diabetes mellitus, hypertension, obesity, and hyperlipidemia.^5,6 Psoriasis is a T-cell mediated disease process driven by IL-23 and T_H17 helper cell–derived proinflammatory cytokines, sharing certain genetic aspects with metabolic syndrome.⁶ Cytokine actions on insulin signaling, lipid metabolism, and adipogenesis may underlie the increased prevalence of metabolic syndrome and cardiovascular risk factors in patients with psoriasis. In addition to treating the cutaneous manifestations of psoriasis, reducing inflammation in these patients reduces C-reactive protein and lipid peroxidation and increases high-density lipoprotein levels.⁶ Tumor necrosis factor α blockers decrease the risk for cardiovascular disease in patients with psoriasis.^7,8 Lower than expected rates of cardiovascular disease also have been reported in a large cohort of psoriasis patients (ie, PSOLAR [Psoriasis Longitudinal Assessment and Registry] registry) being treated with either ustekinumab or tumor necrosis factor α blockers.⁹

Psoriatic arthritis is a chronic inflammatory disease in which active inflammation results in progressive joint destruction.¹⁰ Tumor necrosis factor α inhibitors suppress disease progression, preserve function, and delay destruction of the joints. Ustekinumab also helps control psoriatic arthritis and inhibits radiographic progression of joint disease.¹¹

Importantly, untreated moderate to severe psoriasis is associated with several comorbidities that may lead to early death such as heart attacks and strokes.¹² Furthermore, patients not taking biologic medications may have higher death rates than patients taking biologic medications.⁹ Psoriasis also is associated with tremendous suffering and negative psychosocial effects. The mental and physical impact of the disease is comparable to other major medical conditions (eg, cancer, arthritis, hypertension, heart disease, diabetes, depression).¹³ Patients also may experience physical discomfort from pain and itching.¹⁴ Children with psoriasis may experience bullying, which is associated with an increased number of depressive episodes, thereby increasing their risk for developing psychiatric conditions such as depression and anxiety as adults.¹⁵ The stigma associated with psoriasis may affect patients’ ability to build relationships. Patients with psoriasis experience higher divorce rates than patients with other chronic medical conditions, and direct involvement of genital regions may negatively impact patients’ sex lives. Patients have noted that the stigma of psoriasis also is associated with the inability to obtain employment.¹⁵ Almost one-third of patients with psoriasis who are either not working or are retired base their work status on their skin condition.¹⁶ Furthermore, psoriasis may contribute to economic burden for patients due to indirect costs associated with work absenteeism.¹⁷

Adequate treatment of psoriasis improves patients’ physical and psychological health as well as their ability to function in the workplace. However, despite the benefits of treatment, 30% of patients with severe psoriasis and 53% of patients with moderate psoriasis receive no treatment or only topical medications instead of systemic therapies.¹⁶ The potential adverse events of inadequate psoriasis treatment far outweigh any potential benefits of withholding treatment. Perhaps a boxed warning should be issued for inadequate treatment of psoriasis patients.

The US Food and Drug Administration uses the term boxed warning to highlight potentially dangerous situations associated with prescription drugs. A boxed warning is used when “[T]here is an adverse reaction so serious in proportion to the potential benefit from the drug (e.g., a fatal, life-threatening or permanently disabling adverse reaction) that it is essential that it be considered in assessing the risks and benefits of using the drug.”¹ However, drugs are not the only potential cause of severe adverse outcomes in patients with psoriasis. Untreated psoriasis also is a well-established cause of serious morbidity and mortality. What are the risks of inadequate psoriasis treatment?

Psoriasis is associated with an increased risk for cardiovascular disease.^2-4 Patients with psoriasis also have a higher prevalence of classic cardiovascular risk factors including smoking, diabetes mellitus, hypertension, obesity, and hyperlipidemia.^5,6 Psoriasis is a T-cell mediated disease process driven by IL-23 and T_H17 helper cell–derived proinflammatory cytokines, sharing certain genetic aspects with metabolic syndrome.⁶ Cytokine actions on insulin signaling, lipid metabolism, and adipogenesis may underlie the increased prevalence of metabolic syndrome and cardiovascular risk factors in patients with psoriasis. In addition to treating the cutaneous manifestations of psoriasis, reducing inflammation in these patients reduces C-reactive protein and lipid peroxidation and increases high-density lipoprotein levels.⁶ Tumor necrosis factor α blockers decrease the risk for cardiovascular disease in patients with psoriasis.^7,8 Lower than expected rates of cardiovascular disease also have been reported in a large cohort of psoriasis patients (ie, PSOLAR [Psoriasis Longitudinal Assessment and Registry] registry) being treated with either ustekinumab or tumor necrosis factor α blockers.⁹

Psoriatic arthritis is a chronic inflammatory disease in which active inflammation results in progressive joint destruction.¹⁰ Tumor necrosis factor α inhibitors suppress disease progression, preserve function, and delay destruction of the joints. Ustekinumab also helps control psoriatic arthritis and inhibits radiographic progression of joint disease.¹¹

Importantly, untreated moderate to severe psoriasis is associated with several comorbidities that may lead to early death such as heart attacks and strokes.¹² Furthermore, patients not taking biologic medications may have higher death rates than patients taking biologic medications.⁹ Psoriasis also is associated with tremendous suffering and negative psychosocial effects. The mental and physical impact of the disease is comparable to other major medical conditions (eg, cancer, arthritis, hypertension, heart disease, diabetes, depression).¹³ Patients also may experience physical discomfort from pain and itching.¹⁴ Children with psoriasis may experience bullying, which is associated with an increased number of depressive episodes, thereby increasing their risk for developing psychiatric conditions such as depression and anxiety as adults.¹⁵ The stigma associated with psoriasis may affect patients’ ability to build relationships. Patients with psoriasis experience higher divorce rates than patients with other chronic medical conditions, and direct involvement of genital regions may negatively impact patients’ sex lives. Patients have noted that the stigma of psoriasis also is associated with the inability to obtain employment.¹⁵ Almost one-third of patients with psoriasis who are either not working or are retired base their work status on their skin condition.¹⁶ Furthermore, psoriasis may contribute to economic burden for patients due to indirect costs associated with work absenteeism.¹⁷

Adequate treatment of psoriasis improves patients’ physical and psychological health as well as their ability to function in the workplace. However, despite the benefits of treatment, 30% of patients with severe psoriasis and 53% of patients with moderate psoriasis receive no treatment or only topical medications instead of systemic therapies.¹⁶ The potential adverse events of inadequate psoriasis treatment far outweigh any potential benefits of withholding treatment. Perhaps a boxed warning should be issued for inadequate treatment of psoriasis patients.

The US Food and Drug Administration uses the term boxed warning to highlight potentially dangerous situations associated with prescription drugs. A boxed warning is used when “[T]here is an adverse reaction so serious in proportion to the potential benefit from the drug (e.g., a fatal, life-threatening or permanently disabling adverse reaction) that it is essential that it be considered in assessing the risks and benefits of using the drug.”¹ However, drugs are not the only potential cause of severe adverse outcomes in patients with psoriasis. Untreated psoriasis also is a well-established cause of serious morbidity and mortality. What are the risks of inadequate psoriasis treatment?

Psoriasis is associated with an increased risk for cardiovascular disease.^2-4 Patients with psoriasis also have a higher prevalence of classic cardiovascular risk factors including smoking, diabetes mellitus, hypertension, obesity, and hyperlipidemia.^5,6 Psoriasis is a T-cell mediated disease process driven by IL-23 and T_H17 helper cell–derived proinflammatory cytokines, sharing certain genetic aspects with metabolic syndrome.⁶ Cytokine actions on insulin signaling, lipid metabolism, and adipogenesis may underlie the increased prevalence of metabolic syndrome and cardiovascular risk factors in patients with psoriasis. In addition to treating the cutaneous manifestations of psoriasis, reducing inflammation in these patients reduces C-reactive protein and lipid peroxidation and increases high-density lipoprotein levels.⁶ Tumor necrosis factor α blockers decrease the risk for cardiovascular disease in patients with psoriasis.^7,8 Lower than expected rates of cardiovascular disease also have been reported in a large cohort of psoriasis patients (ie, PSOLAR [Psoriasis Longitudinal Assessment and Registry] registry) being treated with either ustekinumab or tumor necrosis factor α blockers.⁹

Psoriatic arthritis is a chronic inflammatory disease in which active inflammation results in progressive joint destruction.¹⁰ Tumor necrosis factor α inhibitors suppress disease progression, preserve function, and delay destruction of the joints. Ustekinumab also helps control psoriatic arthritis and inhibits radiographic progression of joint disease.¹¹

Importantly, untreated moderate to severe psoriasis is associated with several comorbidities that may lead to early death such as heart attacks and strokes.¹² Furthermore, patients not taking biologic medications may have higher death rates than patients taking biologic medications.⁹ Psoriasis also is associated with tremendous suffering and negative psychosocial effects. The mental and physical impact of the disease is comparable to other major medical conditions (eg, cancer, arthritis, hypertension, heart disease, diabetes, depression).¹³ Patients also may experience physical discomfort from pain and itching.¹⁴ Children with psoriasis may experience bullying, which is associated with an increased number of depressive episodes, thereby increasing their risk for developing psychiatric conditions such as depression and anxiety as adults.¹⁵ The stigma associated with psoriasis may affect patients’ ability to build relationships. Patients with psoriasis experience higher divorce rates than patients with other chronic medical conditions, and direct involvement of genital regions may negatively impact patients’ sex lives. Patients have noted that the stigma of psoriasis also is associated with the inability to obtain employment.¹⁵ Almost one-third of patients with psoriasis who are either not working or are retired base their work status on their skin condition.¹⁶ Furthermore, psoriasis may contribute to economic burden for patients due to indirect costs associated with work absenteeism.¹⁷

Adequate treatment of psoriasis improves patients’ physical and psychological health as well as their ability to function in the workplace. However, despite the benefits of treatment, 30% of patients with severe psoriasis and 53% of patients with moderate psoriasis receive no treatment or only topical medications instead of systemic therapies.¹⁶ The potential adverse events of inadequate psoriasis treatment far outweigh any potential benefits of withholding treatment. Perhaps a boxed warning should be issued for inadequate treatment of psoriasis patients.

To the Editor:

We report 2 cases of desmoplastic hairless hypopigmented nevi (DHHN), which are giant congenital melanocytic nevi (GCMN) that show sclerosis with progressive loss of pigment and hair. These changes in GCMN could be considered signs of regression.

A 6-year-old boy presented in the dermatology department with an asymptomatic skin lesion on the right buttock since birth. The parents claimed that the lesion was darkly pigmented at birth and gradually increased in size, with progressive reduction in color in the last 2 years. Physical examination revealed a 10×6-cm, well-defined, raised plaque on the upper medial side of the right buttock (Figure 1). The plaque was firm with a shiny smooth surface and was devoid of hair. The surface was flesh colored with scattered pigmented spots. A punch biopsy of the lesion showed increased melanin content in the basal cell layer. The upper dermis showed small nests of epithelioid nevus cells, most of them containing melanin pigment (Figure 2). In the lower two-thirds of the dermis, nevus cells were both epithelioid and spindle shaped and were arranged in between thick sclerotic collagen bundles with an increased number of fibroblasts. There was a marked reduction in the number of hair follicles. Immunohistochemical staining results were S-100 positive and CD34 negative.

A 5-year-old boy presented in the dermatology department with a large hairy GCMN covering most of the trunk since birth. In the last 1.5 years the parents noted gradual fading of color, decreased hair density, and increased induration of the nevus. Physical examination revealed a large plaque covering the anterior aspect of the trunk (Figure 3) and the back extending down to the buttocks. The lesion formed large skin folds that were more pronounced on the back. The nevus was darkly pigmented with large areas of lighter color that were indurated, devoid of hair, and showed small spots of dark pigmentation. A punch biopsy from the lesion showed small nests of nevus cells in the upper part of the reticular dermis. In the lower part of the dermis, nevus cells were arranged in single units in between thick collagen bundles.

In 2003, Ruiz-Maldonado et al¹ described 4 cases of GCMN that showed progressive loss of pigmentation, sclerosis, and hair loss. They proposed the term desmoplastic hairless hypopigmented nevus for their cases and considered it as a variant of GCMN.¹ Prior to these reported cases, 2 similar cases were described. The first was a report by Hogan et al² in 1988 of a 7-month-old girl with a GCMN involving the occipital area and the upper back that became indurated and ulcerated with progressive involution that led to complete disappearance of the nevus. The second was a report by Pattee et al³ in 2001 of a newborn with a GCMN located on the trunk with progressive sclerodermiform reaction. After surgical excision of the nevus, the sclerotic margin disappeared.³

Following the report by Ruiz-Maldonaldo et al,¹ 5 more cases of DHHN were described.^4-8 All cases of DHHN share the same clinical and histopathological features. The clinical features include a GCMN present since birth with progressive sclerosis over time and loss of both pigmentation and hair. Histologically, DHHN shows the typical changes of a congenital melanocytic nevus with decreased numbers of nevus cells, thick sclerotic collagen bundles of the reticular dermis, increased number of fibroblasts, and decreased number of hair follicles. The progressive reduction in the number of nevus cells in melanocytic nevi is considered a sign of regression. Spontaneous regression was rarely described in GCMN, and all the reported cases of regression were associated with desmoplasia.⁴ Desmoplasia is thought to be induced by either melanocytes that function as adaptive fibroblasts or by fibroblasts themselves, as fibroblasts can show multifunctional differentiation capabilities.⁹ The direct correlation between the increased induration of DHHN and pigment depletion supports the former hypothesis. The absence of inflammatory cells within the sections of DHHN lesions is against the possibility of an immune-mediated reaction as a cause for the clinical and histological changes seen in this rare form of GCMN. The progressive hair loss in DHHN may be explained by the progressive fibrotic changes in the reticular dermis that affect the blood supply to follicles, leading to atrophy or even absence of the follicles. The progressive reduction in the number of nevus cells in DHHN reduces the potential for malignant transformation and hence following a watchful waiting strategy is a reasonable way to manage these nevi.

We present 2 patients with DHHN, which is a rare form of GCMN that shows signs of regression. The cause of these changes is still unclear.

To the Editor:

We report 2 cases of desmoplastic hairless hypopigmented nevi (DHHN), which are giant congenital melanocytic nevi (GCMN) that show sclerosis with progressive loss of pigment and hair. These changes in GCMN could be considered signs of regression.

A 6-year-old boy presented in the dermatology department with an asymptomatic skin lesion on the right buttock since birth. The parents claimed that the lesion was darkly pigmented at birth and gradually increased in size, with progressive reduction in color in the last 2 years. Physical examination revealed a 10×6-cm, well-defined, raised plaque on the upper medial side of the right buttock (Figure 1). The plaque was firm with a shiny smooth surface and was devoid of hair. The surface was flesh colored with scattered pigmented spots. A punch biopsy of the lesion showed increased melanin content in the basal cell layer. The upper dermis showed small nests of epithelioid nevus cells, most of them containing melanin pigment (Figure 2). In the lower two-thirds of the dermis, nevus cells were both epithelioid and spindle shaped and were arranged in between thick sclerotic collagen bundles with an increased number of fibroblasts. There was a marked reduction in the number of hair follicles. Immunohistochemical staining results were S-100 positive and CD34 negative.

A 5-year-old boy presented in the dermatology department with a large hairy GCMN covering most of the trunk since birth. In the last 1.5 years the parents noted gradual fading of color, decreased hair density, and increased induration of the nevus. Physical examination revealed a large plaque covering the anterior aspect of the trunk (Figure 3) and the back extending down to the buttocks. The lesion formed large skin folds that were more pronounced on the back. The nevus was darkly pigmented with large areas of lighter color that were indurated, devoid of hair, and showed small spots of dark pigmentation. A punch biopsy from the lesion showed small nests of nevus cells in the upper part of the reticular dermis. In the lower part of the dermis, nevus cells were arranged in single units in between thick collagen bundles.

In 2003, Ruiz-Maldonado et al¹ described 4 cases of GCMN that showed progressive loss of pigmentation, sclerosis, and hair loss. They proposed the term desmoplastic hairless hypopigmented nevus for their cases and considered it as a variant of GCMN.¹ Prior to these reported cases, 2 similar cases were described. The first was a report by Hogan et al² in 1988 of a 7-month-old girl with a GCMN involving the occipital area and the upper back that became indurated and ulcerated with progressive involution that led to complete disappearance of the nevus. The second was a report by Pattee et al³ in 2001 of a newborn with a GCMN located on the trunk with progressive sclerodermiform reaction. After surgical excision of the nevus, the sclerotic margin disappeared.³

Following the report by Ruiz-Maldonaldo et al,¹ 5 more cases of DHHN were described.^4-8 All cases of DHHN share the same clinical and histopathological features. The clinical features include a GCMN present since birth with progressive sclerosis over time and loss of both pigmentation and hair. Histologically, DHHN shows the typical changes of a congenital melanocytic nevus with decreased numbers of nevus cells, thick sclerotic collagen bundles of the reticular dermis, increased number of fibroblasts, and decreased number of hair follicles. The progressive reduction in the number of nevus cells in melanocytic nevi is considered a sign of regression. Spontaneous regression was rarely described in GCMN, and all the reported cases of regression were associated with desmoplasia.⁴ Desmoplasia is thought to be induced by either melanocytes that function as adaptive fibroblasts or by fibroblasts themselves, as fibroblasts can show multifunctional differentiation capabilities.⁹ The direct correlation between the increased induration of DHHN and pigment depletion supports the former hypothesis. The absence of inflammatory cells within the sections of DHHN lesions is against the possibility of an immune-mediated reaction as a cause for the clinical and histological changes seen in this rare form of GCMN. The progressive hair loss in DHHN may be explained by the progressive fibrotic changes in the reticular dermis that affect the blood supply to follicles, leading to atrophy or even absence of the follicles. The progressive reduction in the number of nevus cells in DHHN reduces the potential for malignant transformation and hence following a watchful waiting strategy is a reasonable way to manage these nevi.

We present 2 patients with DHHN, which is a rare form of GCMN that shows signs of regression. The cause of these changes is still unclear.

To the Editor:

We report 2 cases of desmoplastic hairless hypopigmented nevi (DHHN), which are giant congenital melanocytic nevi (GCMN) that show sclerosis with progressive loss of pigment and hair. These changes in GCMN could be considered signs of regression.

A 6-year-old boy presented in the dermatology department with an asymptomatic skin lesion on the right buttock since birth. The parents claimed that the lesion was darkly pigmented at birth and gradually increased in size, with progressive reduction in color in the last 2 years. Physical examination revealed a 10×6-cm, well-defined, raised plaque on the upper medial side of the right buttock (Figure 1). The plaque was firm with a shiny smooth surface and was devoid of hair. The surface was flesh colored with scattered pigmented spots. A punch biopsy of the lesion showed increased melanin content in the basal cell layer. The upper dermis showed small nests of epithelioid nevus cells, most of them containing melanin pigment (Figure 2). In the lower two-thirds of the dermis, nevus cells were both epithelioid and spindle shaped and were arranged in between thick sclerotic collagen bundles with an increased number of fibroblasts. There was a marked reduction in the number of hair follicles. Immunohistochemical staining results were S-100 positive and CD34 negative.

A 5-year-old boy presented in the dermatology department with a large hairy GCMN covering most of the trunk since birth. In the last 1.5 years the parents noted gradual fading of color, decreased hair density, and increased induration of the nevus. Physical examination revealed a large plaque covering the anterior aspect of the trunk (Figure 3) and the back extending down to the buttocks. The lesion formed large skin folds that were more pronounced on the back. The nevus was darkly pigmented with large areas of lighter color that were indurated, devoid of hair, and showed small spots of dark pigmentation. A punch biopsy from the lesion showed small nests of nevus cells in the upper part of the reticular dermis. In the lower part of the dermis, nevus cells were arranged in single units in between thick collagen bundles.

In 2003, Ruiz-Maldonado et al¹ described 4 cases of GCMN that showed progressive loss of pigmentation, sclerosis, and hair loss. They proposed the term desmoplastic hairless hypopigmented nevus for their cases and considered it as a variant of GCMN.¹ Prior to these reported cases, 2 similar cases were described. The first was a report by Hogan et al² in 1988 of a 7-month-old girl with a GCMN involving the occipital area and the upper back that became indurated and ulcerated with progressive involution that led to complete disappearance of the nevus. The second was a report by Pattee et al³ in 2001 of a newborn with a GCMN located on the trunk with progressive sclerodermiform reaction. After surgical excision of the nevus, the sclerotic margin disappeared.³

Following the report by Ruiz-Maldonaldo et al,¹ 5 more cases of DHHN were described.^4-8 All cases of DHHN share the same clinical and histopathological features. The clinical features include a GCMN present since birth with progressive sclerosis over time and loss of both pigmentation and hair. Histologically, DHHN shows the typical changes of a congenital melanocytic nevus with decreased numbers of nevus cells, thick sclerotic collagen bundles of the reticular dermis, increased number of fibroblasts, and decreased number of hair follicles. The progressive reduction in the number of nevus cells in melanocytic nevi is considered a sign of regression. Spontaneous regression was rarely described in GCMN, and all the reported cases of regression were associated with desmoplasia.⁴ Desmoplasia is thought to be induced by either melanocytes that function as adaptive fibroblasts or by fibroblasts themselves, as fibroblasts can show multifunctional differentiation capabilities.⁹ The direct correlation between the increased induration of DHHN and pigment depletion supports the former hypothesis. The absence of inflammatory cells within the sections of DHHN lesions is against the possibility of an immune-mediated reaction as a cause for the clinical and histological changes seen in this rare form of GCMN. The progressive hair loss in DHHN may be explained by the progressive fibrotic changes in the reticular dermis that affect the blood supply to follicles, leading to atrophy or even absence of the follicles. The progressive reduction in the number of nevus cells in DHHN reduces the potential for malignant transformation and hence following a watchful waiting strategy is a reasonable way to manage these nevi.

We present 2 patients with DHHN, which is a rare form of GCMN that shows signs of regression. The cause of these changes is still unclear.

To the Editor:

Lyell¹ coined the term cutaneous artifactual disease to describe the spectrum of factitious disorders associated with skin presentations. Interestingly, Lyell was the first to name toxic epidermal necrolysis (TEN).^2,3 We present a rare case of factitial TEN, a dangerous and life-threatening manifestation of factitial disease.

A 49-year-old homeless man with a history of Stevens-Johnson syndrome (SJS)/TEN from trimethoprim-sulfamethoxazole (TMP-SMX) was admitted on 4 separate occasions over an 18-month period for recurrent exposure to the medication producing SJS/TEN. Originally, this patient was given TMP-SMX for a skin infection and 10 days later presented with 15% body surface area (BSA) involvement of SJS/TEN. He was successfully treated with intravenous immunoglobulin (IVIg) in the burn intensive care unit (BICU) and discharged. Several months later, the patient was given TMP-SMX for a leg infection by a different clinic. He was admitted to the BICU with 40% BSA, treated with IVIg, and survived. Eight months later, the patient was again admitted to the BICU with 30% BSA and treated with IVIg; however, this admission required intubation due to complications secondary to volume resuscitation. He was evaluated by psychiatry and confessed to purposely seeking TMP-SMX, stating that he “liked the food and care in the hospital.” He was diagnosed with factitial disorder and given a referral for further treatment at an outpatient facility. Two months later, the patient was again admitted to the BICU after taking a single dose of TMP-SMX obtained from a “friend.” He had 10% BSA with conjunctival involvement and was again successfully treated with IVIg. He was discharged with the state psychiatric system for further treatment and evaluation.

Factitial disease in dermatology is difficult to diagnose. Its incidence is unknown, as only case reports exist in the literature. In factitial disease, patients “perform self-mutilating and clinically relevant damage to themselves without the direct intention of suicide.”⁴ Harth et al⁴ described 3 subcategories of factitious disorders: dermatitis artefacta syndrome, dermatitis para-artefacta syndrome, or malingering. Dermatitis artefacta syndrome is “a dissociated self-injury or behavior where the patient unconsciously simulated disease with intention to be cared for as a patient.”⁴ Dermatitis para-artefacta syndrome was described as a disorder of impulse control in which a patient will produce or manipulate a specific dermatosis presentation. The patient usually admits to doing it in a semiconscious state. Dermatitis artefacta and dermatitis para-artefacta differ from malingering in that malingering patients knowingly fake symptoms for external gain, which can be monetary or the avoidance of responsibility.⁴ More familiar examples to dermatologists of factitial disease include factitial panniculitis,¹ direct applications of caustic agents to the skin, and excoriations from instruments or fingernails.^4,5

This case illustrates the difficult and potentially dangerous nature of factitial disorders, specifically dermatitis para-artefacta syndrome. Our patient was intensely preoccupied with the outcome of being a patient in a hospital. Our patient sought out a medication from multiple providers to produce a deadly and severe life-threatening reaction. If his main intentions were solely to obtain a bed and 3 square meals a day, then malingering would have represented his factitial disease. However, his main intent was to be seen as a patient, and then doted on and cared for by medical professionals in a hospital setting. From this assessment, the patient’s behavior would fall under the factitial disorder of dermatitis para-artefacta syndrome.

Factitious disorders pose immense challenges for diagnosis and treatment. It is prudent for physicians to learn to recognize patterns of history and examination that do not coincide. The first step in treatment is the recognition and early involvement of psychiatry to aid in curbing this behavior. Remission of factitial disorders can be induced with proper diagnosis and treatment. Patients with the highest chance of remission are those with treatment centered on behavioral therapy in conjunction with psychotropic medications.¹

To the Editor:

Lyell¹ coined the term cutaneous artifactual disease to describe the spectrum of factitious disorders associated with skin presentations. Interestingly, Lyell was the first to name toxic epidermal necrolysis (TEN).^2,3 We present a rare case of factitial TEN, a dangerous and life-threatening manifestation of factitial disease.

A 49-year-old homeless man with a history of Stevens-Johnson syndrome (SJS)/TEN from trimethoprim-sulfamethoxazole (TMP-SMX) was admitted on 4 separate occasions over an 18-month period for recurrent exposure to the medication producing SJS/TEN. Originally, this patient was given TMP-SMX for a skin infection and 10 days later presented with 15% body surface area (BSA) involvement of SJS/TEN. He was successfully treated with intravenous immunoglobulin (IVIg) in the burn intensive care unit (BICU) and discharged. Several months later, the patient was given TMP-SMX for a leg infection by a different clinic. He was admitted to the BICU with 40% BSA, treated with IVIg, and survived. Eight months later, the patient was again admitted to the BICU with 30% BSA and treated with IVIg; however, this admission required intubation due to complications secondary to volume resuscitation. He was evaluated by psychiatry and confessed to purposely seeking TMP-SMX, stating that he “liked the food and care in the hospital.” He was diagnosed with factitial disorder and given a referral for further treatment at an outpatient facility. Two months later, the patient was again admitted to the BICU after taking a single dose of TMP-SMX obtained from a “friend.” He had 10% BSA with conjunctival involvement and was again successfully treated with IVIg. He was discharged with the state psychiatric system for further treatment and evaluation.

Factitial disease in dermatology is difficult to diagnose. Its incidence is unknown, as only case reports exist in the literature. In factitial disease, patients “perform self-mutilating and clinically relevant damage to themselves without the direct intention of suicide.”⁴ Harth et al⁴ described 3 subcategories of factitious disorders: dermatitis artefacta syndrome, dermatitis para-artefacta syndrome, or malingering. Dermatitis artefacta syndrome is “a dissociated self-injury or behavior where the patient unconsciously simulated disease with intention to be cared for as a patient.”⁴ Dermatitis para-artefacta syndrome was described as a disorder of impulse control in which a patient will produce or manipulate a specific dermatosis presentation. The patient usually admits to doing it in a semiconscious state. Dermatitis artefacta and dermatitis para-artefacta differ from malingering in that malingering patients knowingly fake symptoms for external gain, which can be monetary or the avoidance of responsibility.⁴ More familiar examples to dermatologists of factitial disease include factitial panniculitis,¹ direct applications of caustic agents to the skin, and excoriations from instruments or fingernails.^4,5

This case illustrates the difficult and potentially dangerous nature of factitial disorders, specifically dermatitis para-artefacta syndrome. Our patient was intensely preoccupied with the outcome of being a patient in a hospital. Our patient sought out a medication from multiple providers to produce a deadly and severe life-threatening reaction. If his main intentions were solely to obtain a bed and 3 square meals a day, then malingering would have represented his factitial disease. However, his main intent was to be seen as a patient, and then doted on and cared for by medical professionals in a hospital setting. From this assessment, the patient’s behavior would fall under the factitial disorder of dermatitis para-artefacta syndrome.

Factitious disorders pose immense challenges for diagnosis and treatment. It is prudent for physicians to learn to recognize patterns of history and examination that do not coincide. The first step in treatment is the recognition and early involvement of psychiatry to aid in curbing this behavior. Remission of factitial disorders can be induced with proper diagnosis and treatment. Patients with the highest chance of remission are those with treatment centered on behavioral therapy in conjunction with psychotropic medications.¹

To the Editor:

Lyell¹ coined the term cutaneous artifactual disease to describe the spectrum of factitious disorders associated with skin presentations. Interestingly, Lyell was the first to name toxic epidermal necrolysis (TEN).^2,3 We present a rare case of factitial TEN, a dangerous and life-threatening manifestation of factitial disease.

A 49-year-old homeless man with a history of Stevens-Johnson syndrome (SJS)/TEN from trimethoprim-sulfamethoxazole (TMP-SMX) was admitted on 4 separate occasions over an 18-month period for recurrent exposure to the medication producing SJS/TEN. Originally, this patient was given TMP-SMX for a skin infection and 10 days later presented with 15% body surface area (BSA) involvement of SJS/TEN. He was successfully treated with intravenous immunoglobulin (IVIg) in the burn intensive care unit (BICU) and discharged. Several months later, the patient was given TMP-SMX for a leg infection by a different clinic. He was admitted to the BICU with 40% BSA, treated with IVIg, and survived. Eight months later, the patient was again admitted to the BICU with 30% BSA and treated with IVIg; however, this admission required intubation due to complications secondary to volume resuscitation. He was evaluated by psychiatry and confessed to purposely seeking TMP-SMX, stating that he “liked the food and care in the hospital.” He was diagnosed with factitial disorder and given a referral for further treatment at an outpatient facility. Two months later, the patient was again admitted to the BICU after taking a single dose of TMP-SMX obtained from a “friend.” He had 10% BSA with conjunctival involvement and was again successfully treated with IVIg. He was discharged with the state psychiatric system for further treatment and evaluation.

Factitial disease in dermatology is difficult to diagnose. Its incidence is unknown, as only case reports exist in the literature. In factitial disease, patients “perform self-mutilating and clinically relevant damage to themselves without the direct intention of suicide.”⁴ Harth et al⁴ described 3 subcategories of factitious disorders: dermatitis artefacta syndrome, dermatitis para-artefacta syndrome, or malingering. Dermatitis artefacta syndrome is “a dissociated self-injury or behavior where the patient unconsciously simulated disease with intention to be cared for as a patient.”⁴ Dermatitis para-artefacta syndrome was described as a disorder of impulse control in which a patient will produce or manipulate a specific dermatosis presentation. The patient usually admits to doing it in a semiconscious state. Dermatitis artefacta and dermatitis para-artefacta differ from malingering in that malingering patients knowingly fake symptoms for external gain, which can be monetary or the avoidance of responsibility.⁴ More familiar examples to dermatologists of factitial disease include factitial panniculitis,¹ direct applications of caustic agents to the skin, and excoriations from instruments or fingernails.^4,5

This case illustrates the difficult and potentially dangerous nature of factitial disorders, specifically dermatitis para-artefacta syndrome. Our patient was intensely preoccupied with the outcome of being a patient in a hospital. Our patient sought out a medication from multiple providers to produce a deadly and severe life-threatening reaction. If his main intentions were solely to obtain a bed and 3 square meals a day, then malingering would have represented his factitial disease. However, his main intent was to be seen as a patient, and then doted on and cared for by medical professionals in a hospital setting. From this assessment, the patient’s behavior would fall under the factitial disorder of dermatitis para-artefacta syndrome.

Factitious disorders pose immense challenges for diagnosis and treatment. It is prudent for physicians to learn to recognize patterns of history and examination that do not coincide. The first step in treatment is the recognition and early involvement of psychiatry to aid in curbing this behavior. Remission of factitial disorders can be induced with proper diagnosis and treatment. Patients with the highest chance of remission are those with treatment centered on behavioral therapy in conjunction with psychotropic medications.¹

Pneumococcal conjugate vaccines 7-valent and 13-valent (PCV7/PCV13) in children younger than 5 years of age in Israel were less prominent in meningitis than in nonmeningitis invasive pneumococcal disease (nm-IPD), according to S. Ben-Shimol, MD, and associates.

Between July 2000 and June 2015, 4,168 IPD episodes were reported; 426 (10.2%) were meningitis. The PCV13 serotype (13VT) meningitis rates significantly declined by 93% (incidence rate ratio = 0.07), from 3.6 ± 1.3 in the pre-PCV period to 0.3 in the last year of the study. Also, the 13VT nm-IPD rates significantly declined by 95% (IRR = 0.05), from a rate of 40.0 ± 5.4 in the pre-PCV period to 1.9. The non-13VT meningitis rates significantly increased by 273% (IRR = 3.73), from 0.8 ± 0.3 in the pre-PCV period to 3.0. And the non-13VT nm-IPD rates also significantly increased by 162% (IRR = 2.62), from 4.5 ± 0.8 in the pre-PCV period to 11.8.

CDC/Amanda Mills

The researchers noted that the increase in non-13VT meningitis was partially driven by a sharp and significant increase of serotype 12F, along with the other predominant non-13VT serotypes that caused meningitis: 15B/C, 24F, and 27. The serotypes also were predominant in non-13VT nm-IPD, as were additional serotypes 8, 10A, 33F, 7B and 10B.

“This finding may be attributed to the younger age of children with meningitis and differences in causative serotypes between the two groups, as the decline of the incidence of meningitis and nm-IPD caused by vaccine-serotypes is similar,” researchers concluded. “Continuous monitoring of meningitis and nm-IPD is warranted.”

Find the full study in Vaccine (doi: 10.1016/j.vaccine.2016.07.038).

[email protected]

Pneumococcal conjugate vaccines 7-valent and 13-valent (PCV7/PCV13) in children younger than 5 years of age in Israel were less prominent in meningitis than in nonmeningitis invasive pneumococcal disease (nm-IPD), according to S. Ben-Shimol, MD, and associates.

Between July 2000 and June 2015, 4,168 IPD episodes were reported; 426 (10.2%) were meningitis. The PCV13 serotype (13VT) meningitis rates significantly declined by 93% (incidence rate ratio = 0.07), from 3.6 ± 1.3 in the pre-PCV period to 0.3 in the last year of the study. Also, the 13VT nm-IPD rates significantly declined by 95% (IRR = 0.05), from a rate of 40.0 ± 5.4 in the pre-PCV period to 1.9. The non-13VT meningitis rates significantly increased by 273% (IRR = 3.73), from 0.8 ± 0.3 in the pre-PCV period to 3.0. And the non-13VT nm-IPD rates also significantly increased by 162% (IRR = 2.62), from 4.5 ± 0.8 in the pre-PCV period to 11.8.

CDC/Amanda Mills

The researchers noted that the increase in non-13VT meningitis was partially driven by a sharp and significant increase of serotype 12F, along with the other predominant non-13VT serotypes that caused meningitis: 15B/C, 24F, and 27. The serotypes also were predominant in non-13VT nm-IPD, as were additional serotypes 8, 10A, 33F, 7B and 10B.

“This finding may be attributed to the younger age of children with meningitis and differences in causative serotypes between the two groups, as the decline of the incidence of meningitis and nm-IPD caused by vaccine-serotypes is similar,” researchers concluded. “Continuous monitoring of meningitis and nm-IPD is warranted.”

Find the full study in Vaccine (doi: 10.1016/j.vaccine.2016.07.038).

[email protected]

Pneumococcal conjugate vaccines 7-valent and 13-valent (PCV7/PCV13) in children younger than 5 years of age in Israel were less prominent in meningitis than in nonmeningitis invasive pneumococcal disease (nm-IPD), according to S. Ben-Shimol, MD, and associates.

Between July 2000 and June 2015, 4,168 IPD episodes were reported; 426 (10.2%) were meningitis. The PCV13 serotype (13VT) meningitis rates significantly declined by 93% (incidence rate ratio = 0.07), from 3.6 ± 1.3 in the pre-PCV period to 0.3 in the last year of the study. Also, the 13VT nm-IPD rates significantly declined by 95% (IRR = 0.05), from a rate of 40.0 ± 5.4 in the pre-PCV period to 1.9. The non-13VT meningitis rates significantly increased by 273% (IRR = 3.73), from 0.8 ± 0.3 in the pre-PCV period to 3.0. And the non-13VT nm-IPD rates also significantly increased by 162% (IRR = 2.62), from 4.5 ± 0.8 in the pre-PCV period to 11.8.

CDC/Amanda Mills

The researchers noted that the increase in non-13VT meningitis was partially driven by a sharp and significant increase of serotype 12F, along with the other predominant non-13VT serotypes that caused meningitis: 15B/C, 24F, and 27. The serotypes also were predominant in non-13VT nm-IPD, as were additional serotypes 8, 10A, 33F, 7B and 10B.

“This finding may be attributed to the younger age of children with meningitis and differences in causative serotypes between the two groups, as the decline of the incidence of meningitis and nm-IPD caused by vaccine-serotypes is similar,” researchers concluded. “Continuous monitoring of meningitis and nm-IPD is warranted.”

Find the full study in Vaccine (doi: 10.1016/j.vaccine.2016.07.038).

[email protected]

Researchers have found that veterans misusing opioids were 5.4 times more likely to use heroin than were veterans who did not misuse opioids. The study of 3,396 veterans found that 77% of heroin users reported previous misuse of opioids. The findings were reported in the Journal of Addiction and were based on an analysis of participants in the Veterans Aging Cohort Study (VACS).

Related: Veterans’ Health and Opioid Safety–Contexts, Risks, and Outreach Implications

“Our findings demonstrate a pattern of transitioning from nonmedical use of prescription opioids to heroin use that has only been demonstrated in select populations,” David Fiellin, Yale public health and medical professor and director of the VACS intervention group told a Brown University reporter. “Our findings are unique in that our sample of individuals consisted of patients who were receiving routine medical care for common medical conditions.”

Related:Call for App to Help Opioid Rehab

All study participants reported no lifetime use of heroin or nonmedical use of opioids at baseline. The authors analyzed VACS data of HIV-infected and an age/race/site-matched control group of HIV-uninfected veterans. Annual behavioral assessments were conducted and contained self-reported measures of nonmedical use of prescription opioids and heroin use.

In addition to analyzing opioid use, the study authors also examined the role of gender, race, and use of stimulant drugs in heroin use. Risk of heroin use was greater for men (2.6 times), stimulant drug users (2.1 times), and blacks (2 times).

 Related: Joining Forces to Reduce Opioid-Related Death

“This paper shows that, as a general clinical practice, particularly for this population which does experience a lot of chronic pain and other risks for substance use including PTSD, screening for nonmedical painkiller use, whether you are prescribing an opioid or not, may be effective to prevent even more harmful transitions to heroin or other drugs,” Brandon Marshall, an assistant professor at the Brown University School of Public Health told the Brown University reporter.

Researchers have found that veterans misusing opioids were 5.4 times more likely to use heroin than were veterans who did not misuse opioids. The study of 3,396 veterans found that 77% of heroin users reported previous misuse of opioids. The findings were reported in the Journal of Addiction and were based on an analysis of participants in the Veterans Aging Cohort Study (VACS).

Related: Veterans’ Health and Opioid Safety–Contexts, Risks, and Outreach Implications

“Our findings demonstrate a pattern of transitioning from nonmedical use of prescription opioids to heroin use that has only been demonstrated in select populations,” David Fiellin, Yale public health and medical professor and director of the VACS intervention group told a Brown University reporter. “Our findings are unique in that our sample of individuals consisted of patients who were receiving routine medical care for common medical conditions.”

Related:Call for App to Help Opioid Rehab

All study participants reported no lifetime use of heroin or nonmedical use of opioids at baseline. The authors analyzed VACS data of HIV-infected and an age/race/site-matched control group of HIV-uninfected veterans. Annual behavioral assessments were conducted and contained self-reported measures of nonmedical use of prescription opioids and heroin use.

In addition to analyzing opioid use, the study authors also examined the role of gender, race, and use of stimulant drugs in heroin use. Risk of heroin use was greater for men (2.6 times), stimulant drug users (2.1 times), and blacks (2 times).

 Related: Joining Forces to Reduce Opioid-Related Death

“This paper shows that, as a general clinical practice, particularly for this population which does experience a lot of chronic pain and other risks for substance use including PTSD, screening for nonmedical painkiller use, whether you are prescribing an opioid or not, may be effective to prevent even more harmful transitions to heroin or other drugs,” Brandon Marshall, an assistant professor at the Brown University School of Public Health told the Brown University reporter.

Researchers have found that veterans misusing opioids were 5.4 times more likely to use heroin than were veterans who did not misuse opioids. The study of 3,396 veterans found that 77% of heroin users reported previous misuse of opioids. The findings were reported in the Journal of Addiction and were based on an analysis of participants in the Veterans Aging Cohort Study (VACS).

Related: Veterans’ Health and Opioid Safety–Contexts, Risks, and Outreach Implications

“Our findings demonstrate a pattern of transitioning from nonmedical use of prescription opioids to heroin use that has only been demonstrated in select populations,” David Fiellin, Yale public health and medical professor and director of the VACS intervention group told a Brown University reporter. “Our findings are unique in that our sample of individuals consisted of patients who were receiving routine medical care for common medical conditions.”

Related:Call for App to Help Opioid Rehab

All study participants reported no lifetime use of heroin or nonmedical use of opioids at baseline. The authors analyzed VACS data of HIV-infected and an age/race/site-matched control group of HIV-uninfected veterans. Annual behavioral assessments were conducted and contained self-reported measures of nonmedical use of prescription opioids and heroin use.

In addition to analyzing opioid use, the study authors also examined the role of gender, race, and use of stimulant drugs in heroin use. Risk of heroin use was greater for men (2.6 times), stimulant drug users (2.1 times), and blacks (2 times).

 Related: Joining Forces to Reduce Opioid-Related Death

“This paper shows that, as a general clinical practice, particularly for this population which does experience a lot of chronic pain and other risks for substance use including PTSD, screening for nonmedical painkiller use, whether you are prescribing an opioid or not, may be effective to prevent even more harmful transitions to heroin or other drugs,” Brandon Marshall, an assistant professor at the Brown University School of Public Health told the Brown University reporter.

Following weeks of criticism over dramatic price increases on its EpiPen, Mylan said on Aug. 29 that it will offer a generic version of the life-saving allergy treatment. The generic, which the company says will be identical to the brand product, will sell for $300 for a two-pack, which is half the cost of Mylan’s brand name EpiPens. The news did little to dim the ongoing outcry over the price, for which there are no other competitors on the market. Some called it a marketing ploy, while Robert Weissman, president of the consumer group Public Citizen, said the generic price was still too high, writing in the Huffington Post of “the weirdness of a drug company offering a generic version” of its own brand-name product.

KHN offers answers to some key questions related to Mylan’s generic and breaks down what this development could mean for consumers and the marketplace.

When will I be able to get a generic EpiPen?Mylan, which is the company that markets this treatment, says it will have a product out within a few weeks. Pfizer is the firm that actually manufactures EpiPens. The drug used is the product epinephrine but the patent applies to the auto-injector device used to deliver it.

Will it cost me less?

For some patients, yes. Those who are uninsured, pay a percentage of the drug cost as their insurance copayment or have an unmet prescription deductible will likely pay less for the $300 two-pack generic than for the brand-name version. That’s because what they pay is based on the full price. Many other consumer have insurance with flat-dollar drug copayments, ranging from $10 to $100 for every prescription so they are paying far less than the retail price. Insurers generally set lower copayments for generic drugs than brand. So if a consumer’s health insurer makes the generic available and places it in the generic payment “tier,” the cost per prescription also could fall. In some cases, however, there is a possibility that some people who could benefit from the lower cost generic won’t have access to it. An insurer or pharmacy benefit manager, for example, might not add the generic EpiPen to the formulary, or restrict its availability in some way. That’s because some health plans get such large rebates from brand-name companies as to make the brand-name version cost less than the generic, said Adam Fein, president of Pembroke Consulting. But consumers do not benefit from rebates directly. Instead, it goes to the pharmacy manager, insurer or employer.

Are manufacturer rebates good?

It depends. They can help lower the cost of the drug for insurers and employers, helping slow overall spending and keep costs paid by consumers such as premiums and deductibles lower. “If we didn’t have rebates [spending on drugs] would be at least 35 percent higher,” said Richard Evans, co-founder of SSR Health, who does investment research on the pharmaceutical industry.

Even so, some say rebates should be barred in favor of more transparent prices. Stephen Schondelmeyer, director of the Prime Institute, an independent consulting group that monitors pharmaceutical trends, said discounts don’t make him feel good when his health plan is paying about $700 for EpiPens that it paid $80 for five years ago. “We should outlaw rebates,” said Schondelmeyer, who also helps oversee the University of Minnesota’s health plan. “What rebates are really is a way to overcharge the market. … We are giving the drug industry loans to the tune of billions of dollars … and rarely does it get back to the end consumer.”

Are drugmakers even allowed to create generic versions of their own products?

Many major drugmakers also market their drugs as generics. Called “authorized generics,” such products are identical to the drugs approved by the Food and Drug Administration as part of a manufacturer’s New Drug Application. Drugmakers do not need to go back to the FDA for any further approvals in order to market an authorized generic.

Why would drugmakers want to offer a generic to their own product?

Most authorized generics appear on the market just as a competitor launches a generic of its own. In those cases, the move helps brand manufacturers retain some revenue that might otherwise be lost to competitors because the entry of less costly generics generally results in a sharp drop in brand-name sales. Manufacturers are careful not to release the authorized generic much before it loses patent protection, because it doesn’t want it to undercut sales of its more pricey brand-name product.

So why is Mylan doing this?

Mylan appears to be offering its “authorized generic” in response to complaints about the cost of its brand-name drug, not fear of competition from rivals. It currently controls the market. Pembroke’s Fein said Mylan miscalculated when it raised EpiPen’s price tag from about $100 to $600 over the past decade.

During that time, the firm failed to notice that insurance coverage had changed, Fein said. Instead of flat-dollar copayments, a growing number of consumers now have prescription deductibles they must meet first. That means some consumers are on the hook for the full $600. “They behaved as if everyone had good insurance,” said Fein. And the firm still seems to argue that raising its prices would not hurt most consumers, noting that many had flat copayments of less than $100. But, as the price rose, their insurer or the employer who provides coverage made up the difference, helping fuel premium and deductible increases.

“Premiums are an out-of-pocket cost,” said Schondelmeyer. “That’s what Mylan and other manufacturers have ignored.”

Do authorized generics reduce competition, which is supposed to help lower prices?

Some generic companies argue that is the case, saying a brand-name company jumping in ahead of rivals makes it less attractive for generic makers to bring their own products to market or challenge existing patents held by brand-name companies. But a 2011 Federal Trade Commission report found that authorized generics did not “measurably” reduce the number of patent challenges. The study also said the presence of authorized generics actually resulted in retail generic prices that were 4 to 8 percent lower than they would have been without.

KHN’s coverage of prescription drug development, costs and pricing is supported in part by the Laura and John Arnold Foundation. Julie Appleby reports on the health care law’s implementation, health care treatments and costs, trends in health insurance, and policy affecting hospitals and other medical providers. Her stories have appeared in USA Today, the Washington Post, the Philadelphia Inquirer, MSNBC and others. Before joining KHN, Appleby spent 10 years covering the health care industry and policy at USA Today. She also worked at the San Francisco Chronicle, The Financial Times in London and the Contra Costa Times in Walnut Creek, Calif. She serves on the board of the Association of Health Care Journalists and has a Master of Public Health degree.

Following weeks of criticism over dramatic price increases on its EpiPen, Mylan said on Aug. 29 that it will offer a generic version of the life-saving allergy treatment. The generic, which the company says will be identical to the brand product, will sell for $300 for a two-pack, which is half the cost of Mylan’s brand name EpiPens. The news did little to dim the ongoing outcry over the price, for which there are no other competitors on the market. Some called it a marketing ploy, while Robert Weissman, president of the consumer group Public Citizen, said the generic price was still too high, writing in the Huffington Post of “the weirdness of a drug company offering a generic version” of its own brand-name product.

KHN offers answers to some key questions related to Mylan’s generic and breaks down what this development could mean for consumers and the marketplace.

When will I be able to get a generic EpiPen?Mylan, which is the company that markets this treatment, says it will have a product out within a few weeks. Pfizer is the firm that actually manufactures EpiPens. The drug used is the product epinephrine but the patent applies to the auto-injector device used to deliver it.

Will it cost me less?

For some patients, yes. Those who are uninsured, pay a percentage of the drug cost as their insurance copayment or have an unmet prescription deductible will likely pay less for the $300 two-pack generic than for the brand-name version. That’s because what they pay is based on the full price. Many other consumer have insurance with flat-dollar drug copayments, ranging from $10 to $100 for every prescription so they are paying far less than the retail price. Insurers generally set lower copayments for generic drugs than brand. So if a consumer’s health insurer makes the generic available and places it in the generic payment “tier,” the cost per prescription also could fall. In some cases, however, there is a possibility that some people who could benefit from the lower cost generic won’t have access to it. An insurer or pharmacy benefit manager, for example, might not add the generic EpiPen to the formulary, or restrict its availability in some way. That’s because some health plans get such large rebates from brand-name companies as to make the brand-name version cost less than the generic, said Adam Fein, president of Pembroke Consulting. But consumers do not benefit from rebates directly. Instead, it goes to the pharmacy manager, insurer or employer.

Are manufacturer rebates good?

It depends. They can help lower the cost of the drug for insurers and employers, helping slow overall spending and keep costs paid by consumers such as premiums and deductibles lower. “If we didn’t have rebates [spending on drugs] would be at least 35 percent higher,” said Richard Evans, co-founder of SSR Health, who does investment research on the pharmaceutical industry.

Even so, some say rebates should be barred in favor of more transparent prices. Stephen Schondelmeyer, director of the Prime Institute, an independent consulting group that monitors pharmaceutical trends, said discounts don’t make him feel good when his health plan is paying about $700 for EpiPens that it paid $80 for five years ago. “We should outlaw rebates,” said Schondelmeyer, who also helps oversee the University of Minnesota’s health plan. “What rebates are really is a way to overcharge the market. … We are giving the drug industry loans to the tune of billions of dollars … and rarely does it get back to the end consumer.”

Are drugmakers even allowed to create generic versions of their own products?

Many major drugmakers also market their drugs as generics. Called “authorized generics,” such products are identical to the drugs approved by the Food and Drug Administration as part of a manufacturer’s New Drug Application. Drugmakers do not need to go back to the FDA for any further approvals in order to market an authorized generic.

Why would drugmakers want to offer a generic to their own product?

Most authorized generics appear on the market just as a competitor launches a generic of its own. In those cases, the move helps brand manufacturers retain some revenue that might otherwise be lost to competitors because the entry of less costly generics generally results in a sharp drop in brand-name sales. Manufacturers are careful not to release the authorized generic much before it loses patent protection, because it doesn’t want it to undercut sales of its more pricey brand-name product.

So why is Mylan doing this?

Mylan appears to be offering its “authorized generic” in response to complaints about the cost of its brand-name drug, not fear of competition from rivals. It currently controls the market. Pembroke’s Fein said Mylan miscalculated when it raised EpiPen’s price tag from about $100 to $600 over the past decade.

During that time, the firm failed to notice that insurance coverage had changed, Fein said. Instead of flat-dollar copayments, a growing number of consumers now have prescription deductibles they must meet first. That means some consumers are on the hook for the full $600. “They behaved as if everyone had good insurance,” said Fein. And the firm still seems to argue that raising its prices would not hurt most consumers, noting that many had flat copayments of less than $100. But, as the price rose, their insurer or the employer who provides coverage made up the difference, helping fuel premium and deductible increases.

“Premiums are an out-of-pocket cost,” said Schondelmeyer. “That’s what Mylan and other manufacturers have ignored.”

Do authorized generics reduce competition, which is supposed to help lower prices?

Some generic companies argue that is the case, saying a brand-name company jumping in ahead of rivals makes it less attractive for generic makers to bring their own products to market or challenge existing patents held by brand-name companies. But a 2011 Federal Trade Commission report found that authorized generics did not “measurably” reduce the number of patent challenges. The study also said the presence of authorized generics actually resulted in retail generic prices that were 4 to 8 percent lower than they would have been without.

KHN’s coverage of prescription drug development, costs and pricing is supported in part by the Laura and John Arnold Foundation. Julie Appleby reports on the health care law’s implementation, health care treatments and costs, trends in health insurance, and policy affecting hospitals and other medical providers. Her stories have appeared in USA Today, the Washington Post, the Philadelphia Inquirer, MSNBC and others. Before joining KHN, Appleby spent 10 years covering the health care industry and policy at USA Today. She also worked at the San Francisco Chronicle, The Financial Times in London and the Contra Costa Times in Walnut Creek, Calif. She serves on the board of the Association of Health Care Journalists and has a Master of Public Health degree.

Following weeks of criticism over dramatic price increases on its EpiPen, Mylan said on Aug. 29 that it will offer a generic version of the life-saving allergy treatment. The generic, which the company says will be identical to the brand product, will sell for $300 for a two-pack, which is half the cost of Mylan’s brand name EpiPens. The news did little to dim the ongoing outcry over the price, for which there are no other competitors on the market. Some called it a marketing ploy, while Robert Weissman, president of the consumer group Public Citizen, said the generic price was still too high, writing in the Huffington Post of “the weirdness of a drug company offering a generic version” of its own brand-name product.

KHN offers answers to some key questions related to Mylan’s generic and breaks down what this development could mean for consumers and the marketplace.

When will I be able to get a generic EpiPen?Mylan, which is the company that markets this treatment, says it will have a product out within a few weeks. Pfizer is the firm that actually manufactures EpiPens. The drug used is the product epinephrine but the patent applies to the auto-injector device used to deliver it.

Will it cost me less?

For some patients, yes. Those who are uninsured, pay a percentage of the drug cost as their insurance copayment or have an unmet prescription deductible will likely pay less for the $300 two-pack generic than for the brand-name version. That’s because what they pay is based on the full price. Many other consumer have insurance with flat-dollar drug copayments, ranging from $10 to $100 for every prescription so they are paying far less than the retail price. Insurers generally set lower copayments for generic drugs than brand. So if a consumer’s health insurer makes the generic available and places it in the generic payment “tier,” the cost per prescription also could fall. In some cases, however, there is a possibility that some people who could benefit from the lower cost generic won’t have access to it. An insurer or pharmacy benefit manager, for example, might not add the generic EpiPen to the formulary, or restrict its availability in some way. That’s because some health plans get such large rebates from brand-name companies as to make the brand-name version cost less than the generic, said Adam Fein, president of Pembroke Consulting. But consumers do not benefit from rebates directly. Instead, it goes to the pharmacy manager, insurer or employer.

Are manufacturer rebates good?

It depends. They can help lower the cost of the drug for insurers and employers, helping slow overall spending and keep costs paid by consumers such as premiums and deductibles lower. “If we didn’t have rebates [spending on drugs] would be at least 35 percent higher,” said Richard Evans, co-founder of SSR Health, who does investment research on the pharmaceutical industry.

Even so, some say rebates should be barred in favor of more transparent prices. Stephen Schondelmeyer, director of the Prime Institute, an independent consulting group that monitors pharmaceutical trends, said discounts don’t make him feel good when his health plan is paying about $700 for EpiPens that it paid $80 for five years ago. “We should outlaw rebates,” said Schondelmeyer, who also helps oversee the University of Minnesota’s health plan. “What rebates are really is a way to overcharge the market. … We are giving the drug industry loans to the tune of billions of dollars … and rarely does it get back to the end consumer.”

Are drugmakers even allowed to create generic versions of their own products?

Many major drugmakers also market their drugs as generics. Called “authorized generics,” such products are identical to the drugs approved by the Food and Drug Administration as part of a manufacturer’s New Drug Application. Drugmakers do not need to go back to the FDA for any further approvals in order to market an authorized generic.

Why would drugmakers want to offer a generic to their own product?

Most authorized generics appear on the market just as a competitor launches a generic of its own. In those cases, the move helps brand manufacturers retain some revenue that might otherwise be lost to competitors because the entry of less costly generics generally results in a sharp drop in brand-name sales. Manufacturers are careful not to release the authorized generic much before it loses patent protection, because it doesn’t want it to undercut sales of its more pricey brand-name product.

So why is Mylan doing this?

Mylan appears to be offering its “authorized generic” in response to complaints about the cost of its brand-name drug, not fear of competition from rivals. It currently controls the market. Pembroke’s Fein said Mylan miscalculated when it raised EpiPen’s price tag from about $100 to $600 over the past decade.

During that time, the firm failed to notice that insurance coverage had changed, Fein said. Instead of flat-dollar copayments, a growing number of consumers now have prescription deductibles they must meet first. That means some consumers are on the hook for the full $600. “They behaved as if everyone had good insurance,” said Fein. And the firm still seems to argue that raising its prices would not hurt most consumers, noting that many had flat copayments of less than $100. But, as the price rose, their insurer or the employer who provides coverage made up the difference, helping fuel premium and deductible increases.

“Premiums are an out-of-pocket cost,” said Schondelmeyer. “That’s what Mylan and other manufacturers have ignored.”

Do authorized generics reduce competition, which is supposed to help lower prices?

Some generic companies argue that is the case, saying a brand-name company jumping in ahead of rivals makes it less attractive for generic makers to bring their own products to market or challenge existing patents held by brand-name companies. But a 2011 Federal Trade Commission report found that authorized generics did not “measurably” reduce the number of patent challenges. The study also said the presence of authorized generics actually resulted in retail generic prices that were 4 to 8 percent lower than they would have been without.

KHN’s coverage of prescription drug development, costs and pricing is supported in part by the Laura and John Arnold Foundation. Julie Appleby reports on the health care law’s implementation, health care treatments and costs, trends in health insurance, and policy affecting hospitals and other medical providers. Her stories have appeared in USA Today, the Washington Post, the Philadelphia Inquirer, MSNBC and others. Before joining KHN, Appleby spent 10 years covering the health care industry and policy at USA Today. She also worked at the San Francisco Chronicle, The Financial Times in London and the Contra Costa Times in Walnut Creek, Calif. She serves on the board of the Association of Health Care Journalists and has a Master of Public Health degree.

Adults with knee osteoarthritis and at least one comorbid condition significantly improved their physical function after a comorbidity-targeted 20-week exercise program in a randomized, controlled trial of 126 patients.

“Guidelines on knee osteoarthritis do not provide guidance on tailoring exercise therapy to the presence of comorbidity,” wrote Mariëtte de Rooij of the Amsterdam Rehabilitation Research Center and her colleagues. “In clinical practice, comorbidity is a frequent reason to exclude patients from exercise therapy,” they noted.

©decade3d/Thinkstock

The researchers randomized 126 adults with knee osteoarthritis and at least one of the following comorbidities: coronary disease, heart failure, type 2 diabetes, chronic obstructive pulmonary disease, or obesity (body mass index 30 kg/m² or higher). The treatment group participated in a 20-week exercise program adapted to their comorbidities and physical limitations. Each program included aerobic exercise and strength training in two 30- to 60-minute sessions per week, supervised by a physical therapist. The control group received their current medical care for knee osteoarthritis and were placed on a waiting list for exercise therapy. Baseline characteristics and demographics were similar between the two groups, with mean ages of about 63 years, 81% with bilateral knee osteoarthritis, and a mean duration of symptoms of about 9 years. Patients with absolute contraindications for exercise therapy (such as myocardial infarction within the past 3 months) were excluded (Arthritis Care Res. 2016 Aug 26. doi: 10.1002/acr.23013).

In a follow-up visit 3 months after the end of the exercise program, patients in the treatment group averaged an 11.6-point (33%) improvement on the Western Ontario and McMaster Universities Osteoarthritis Index physical function subscale and a 59-meter (15%) improvement on the 6-minute walk test, compared with controls.

In addition, patients in the treatment group reported a 1.7-point (27%) improvement on the Numeric Rating Scale for knee pain severity. No serious adverse events related to the exercise therapy were reported.

The exercise programs were adapted to the patients by adjusting the frequency, intensity, timing, and type (FITT) of exercises, educating patients about the impact of exercise on their comorbidities, and by coaching patients to ease fears of exertion or to encourage weight loss.

“This is the first study showing that tailored exercise therapy is efficacious in improving physical functioning and is safe in patients with knee osteoarthritis and severe comorbidities,” the researchers said. The findings were limited by several factors including a small sample size that made it impossible to analyze the impact of exercise on any specific comorbidity, and the lack of cost-effectiveness data. However, “the results should encourage clinicians to consider exercise therapy as a treatment option for patients with knee osteoarthritis, even in the presence of severe comorbidity,” the researchers added.

The trial was supported by the Royal Dutch Society for Physical Therapy and Merck Sharp & Dohme. The researchers had no financial conflicts to disclose.

Adults with knee osteoarthritis and at least one comorbid condition significantly improved their physical function after a comorbidity-targeted 20-week exercise program in a randomized, controlled trial of 126 patients.

“Guidelines on knee osteoarthritis do not provide guidance on tailoring exercise therapy to the presence of comorbidity,” wrote Mariëtte de Rooij of the Amsterdam Rehabilitation Research Center and her colleagues. “In clinical practice, comorbidity is a frequent reason to exclude patients from exercise therapy,” they noted.

©decade3d/Thinkstock

The researchers randomized 126 adults with knee osteoarthritis and at least one of the following comorbidities: coronary disease, heart failure, type 2 diabetes, chronic obstructive pulmonary disease, or obesity (body mass index 30 kg/m² or higher). The treatment group participated in a 20-week exercise program adapted to their comorbidities and physical limitations. Each program included aerobic exercise and strength training in two 30- to 60-minute sessions per week, supervised by a physical therapist. The control group received their current medical care for knee osteoarthritis and were placed on a waiting list for exercise therapy. Baseline characteristics and demographics were similar between the two groups, with mean ages of about 63 years, 81% with bilateral knee osteoarthritis, and a mean duration of symptoms of about 9 years. Patients with absolute contraindications for exercise therapy (such as myocardial infarction within the past 3 months) were excluded (Arthritis Care Res. 2016 Aug 26. doi: 10.1002/acr.23013).

In a follow-up visit 3 months after the end of the exercise program, patients in the treatment group averaged an 11.6-point (33%) improvement on the Western Ontario and McMaster Universities Osteoarthritis Index physical function subscale and a 59-meter (15%) improvement on the 6-minute walk test, compared with controls.

In addition, patients in the treatment group reported a 1.7-point (27%) improvement on the Numeric Rating Scale for knee pain severity. No serious adverse events related to the exercise therapy were reported.

The exercise programs were adapted to the patients by adjusting the frequency, intensity, timing, and type (FITT) of exercises, educating patients about the impact of exercise on their comorbidities, and by coaching patients to ease fears of exertion or to encourage weight loss.

“This is the first study showing that tailored exercise therapy is efficacious in improving physical functioning and is safe in patients with knee osteoarthritis and severe comorbidities,” the researchers said. The findings were limited by several factors including a small sample size that made it impossible to analyze the impact of exercise on any specific comorbidity, and the lack of cost-effectiveness data. However, “the results should encourage clinicians to consider exercise therapy as a treatment option for patients with knee osteoarthritis, even in the presence of severe comorbidity,” the researchers added.

The trial was supported by the Royal Dutch Society for Physical Therapy and Merck Sharp & Dohme. The researchers had no financial conflicts to disclose.

Adults with knee osteoarthritis and at least one comorbid condition significantly improved their physical function after a comorbidity-targeted 20-week exercise program in a randomized, controlled trial of 126 patients.

“Guidelines on knee osteoarthritis do not provide guidance on tailoring exercise therapy to the presence of comorbidity,” wrote Mariëtte de Rooij of the Amsterdam Rehabilitation Research Center and her colleagues. “In clinical practice, comorbidity is a frequent reason to exclude patients from exercise therapy,” they noted.

©decade3d/Thinkstock

The researchers randomized 126 adults with knee osteoarthritis and at least one of the following comorbidities: coronary disease, heart failure, type 2 diabetes, chronic obstructive pulmonary disease, or obesity (body mass index 30 kg/m² or higher). The treatment group participated in a 20-week exercise program adapted to their comorbidities and physical limitations. Each program included aerobic exercise and strength training in two 30- to 60-minute sessions per week, supervised by a physical therapist. The control group received their current medical care for knee osteoarthritis and were placed on a waiting list for exercise therapy. Baseline characteristics and demographics were similar between the two groups, with mean ages of about 63 years, 81% with bilateral knee osteoarthritis, and a mean duration of symptoms of about 9 years. Patients with absolute contraindications for exercise therapy (such as myocardial infarction within the past 3 months) were excluded (Arthritis Care Res. 2016 Aug 26. doi: 10.1002/acr.23013).

In a follow-up visit 3 months after the end of the exercise program, patients in the treatment group averaged an 11.6-point (33%) improvement on the Western Ontario and McMaster Universities Osteoarthritis Index physical function subscale and a 59-meter (15%) improvement on the 6-minute walk test, compared with controls.

In addition, patients in the treatment group reported a 1.7-point (27%) improvement on the Numeric Rating Scale for knee pain severity. No serious adverse events related to the exercise therapy were reported.

The exercise programs were adapted to the patients by adjusting the frequency, intensity, timing, and type (FITT) of exercises, educating patients about the impact of exercise on their comorbidities, and by coaching patients to ease fears of exertion or to encourage weight loss.

“This is the first study showing that tailored exercise therapy is efficacious in improving physical functioning and is safe in patients with knee osteoarthritis and severe comorbidities,” the researchers said. The findings were limited by several factors including a small sample size that made it impossible to analyze the impact of exercise on any specific comorbidity, and the lack of cost-effectiveness data. However, “the results should encourage clinicians to consider exercise therapy as a treatment option for patients with knee osteoarthritis, even in the presence of severe comorbidity,” the researchers added.

The trial was supported by the Royal Dutch Society for Physical Therapy and Merck Sharp & Dohme. The researchers had no financial conflicts to disclose.

The most recent update of the American Society of Clinical Oncology and College of American Pathologists (ASCO-CAP) guidelines for interpreting HER2 diagnostic assays affected about 5% of breast cancer patients in three large clinical trials, researchers reported in the Journal of Clinical Oncology.

Although this is “a small minority of patients,” clinical correlates fail to support three of the five groups of patients that the updated guidelines designated based on HER2 FISH [fluorescent in situ hybridization] ratio and average number of HER2 gene copies per tumor cell, said Michael Press, MD, of the University of Southern California Norris Comprehensive Cancer Center, Los Angeles, and his associates.

“Our findings support the original categorizations of HER2 by FISH status in BCIRG [Breast Cancer International Research Group]/Translational Research in Oncology trials,” they said.

The most recent ASCO-CAP guidelines differ from Food and Drug Administration–approved package inserts for HER2 FISH companion diagnostic assays, which reflect the criteria used in clinical trials of the BCIRG/Translational Research in Oncology (TRIO) and previous (2007) ASCO-CAP guidelines, the researchers noted. In particular, the updated guidelines split patients into group 1 (in situ hybridization [ISH] positive, with a HER2-to-chromosome 17 centromere ratio of at least 2.0 and an average of at least four copies of the HER2 gene per tumor cell), group 2 (ISH positive, with a ratio of at least 2.0 and less than four HER2 gene copies), group 3 (ISH positive, with a ratio of less than 2.0 and at least six gene copies), group 4 (ISH equivocal, with a ratio of less than 2.0 and at least four but fewer than six gene copies), and group 5 (ISH negative, a ratio of less than 2.0 and fewer than four gene copies).

The researchers retrospectively analyzed detailed outcomes data from the BCIRG-005, BCIRG- 006, and BCIRG-007 clinical trials, which “now have long-term clinical follow-up data available that facilitate determination of whether the new HER2 guidelines for FISH are clinically useful and predictive of known outcomes,” they said.

The investigators counted cases in each of the five groups and looked to see if these groups correlated with the clinical implications of HER2 gene amplification, such as overexpression of HER2 protein and worse disease-free and overall survival without HER2 targeted therapy (J Clin Oncol. 2016 Aug 29. doi: 10.1200/JCO.2016.66.6693).

Among 10,468 patients in these trials, the vast majority fell into group 1 (41%) or 5 (54%), while 0.7% were in group 2, 0.5% were in group 3, and 4% were in group 4. HER2 amplification status did not change for most patients because the updated guidelines did not affect group 1 (amplified) or group 5 (not amplified). But groups 2 and 4, which the guidelines respectively designated as ISH positive and ISH equivocal, actually seemed to be HER2 not amplified, as neither group was associated with HER2 protein overexpression, group 2 showed a lack of response to trastuzumab therapy, and patients in group 4 who received only chemotherapy had a prognosis similar to that of group 5 in terms of disease-free and overall survival, the researchers reported.

“Overall, we observe approximately 99.3% agreement with initial FDA-approved guidelines and 94.7% agreement with current ASCO-CAP guidelines,” they wrote. “The 4.6% differential is related to only two groups, groups 3 and 4, introduced by ASCO-CAP that lead to different assessments of HER2 status, compared with FDA criteria. Finally, our observations indicate group 2, which represents 0.7% of breast cancers, is misclassified by both the FDA and ASCO-CAP guidelines as amplified and ISH positive.”

They also found that patients in group 3, which the guidelines designated as ISH positive, actually had both HER2 amplified and HER2 not-amplified breast cancers. “There are now nearly 3 decades of accumulated experience and published data studying this alteration in human breast cancers,” the investigators concluded. “Although guidelines are helpful, diagnostic judgment and long-term outcome data remain important in the evaluation of testing criteria.”

The most recent update of the American Society of Clinical Oncology and College of American Pathologists (ASCO-CAP) guidelines for interpreting HER2 diagnostic assays affected about 5% of breast cancer patients in three large clinical trials, researchers reported in the Journal of Clinical Oncology.

Although this is “a small minority of patients,” clinical correlates fail to support three of the five groups of patients that the updated guidelines designated based on HER2 FISH [fluorescent in situ hybridization] ratio and average number of HER2 gene copies per tumor cell, said Michael Press, MD, of the University of Southern California Norris Comprehensive Cancer Center, Los Angeles, and his associates.

“Our findings support the original categorizations of HER2 by FISH status in BCIRG [Breast Cancer International Research Group]/Translational Research in Oncology trials,” they said.

The most recent ASCO-CAP guidelines differ from Food and Drug Administration–approved package inserts for HER2 FISH companion diagnostic assays, which reflect the criteria used in clinical trials of the BCIRG/Translational Research in Oncology (TRIO) and previous (2007) ASCO-CAP guidelines, the researchers noted. In particular, the updated guidelines split patients into group 1 (in situ hybridization [ISH] positive, with a HER2-to-chromosome 17 centromere ratio of at least 2.0 and an average of at least four copies of the HER2 gene per tumor cell), group 2 (ISH positive, with a ratio of at least 2.0 and less than four HER2 gene copies), group 3 (ISH positive, with a ratio of less than 2.0 and at least six gene copies), group 4 (ISH equivocal, with a ratio of less than 2.0 and at least four but fewer than six gene copies), and group 5 (ISH negative, a ratio of less than 2.0 and fewer than four gene copies).

The researchers retrospectively analyzed detailed outcomes data from the BCIRG-005, BCIRG- 006, and BCIRG-007 clinical trials, which “now have long-term clinical follow-up data available that facilitate determination of whether the new HER2 guidelines for FISH are clinically useful and predictive of known outcomes,” they said.

The investigators counted cases in each of the five groups and looked to see if these groups correlated with the clinical implications of HER2 gene amplification, such as overexpression of HER2 protein and worse disease-free and overall survival without HER2 targeted therapy (J Clin Oncol. 2016 Aug 29. doi: 10.1200/JCO.2016.66.6693).

Among 10,468 patients in these trials, the vast majority fell into group 1 (41%) or 5 (54%), while 0.7% were in group 2, 0.5% were in group 3, and 4% were in group 4. HER2 amplification status did not change for most patients because the updated guidelines did not affect group 1 (amplified) or group 5 (not amplified). But groups 2 and 4, which the guidelines respectively designated as ISH positive and ISH equivocal, actually seemed to be HER2 not amplified, as neither group was associated with HER2 protein overexpression, group 2 showed a lack of response to trastuzumab therapy, and patients in group 4 who received only chemotherapy had a prognosis similar to that of group 5 in terms of disease-free and overall survival, the researchers reported.

“Overall, we observe approximately 99.3% agreement with initial FDA-approved guidelines and 94.7% agreement with current ASCO-CAP guidelines,” they wrote. “The 4.6% differential is related to only two groups, groups 3 and 4, introduced by ASCO-CAP that lead to different assessments of HER2 status, compared with FDA criteria. Finally, our observations indicate group 2, which represents 0.7% of breast cancers, is misclassified by both the FDA and ASCO-CAP guidelines as amplified and ISH positive.”

They also found that patients in group 3, which the guidelines designated as ISH positive, actually had both HER2 amplified and HER2 not-amplified breast cancers. “There are now nearly 3 decades of accumulated experience and published data studying this alteration in human breast cancers,” the investigators concluded. “Although guidelines are helpful, diagnostic judgment and long-term outcome data remain important in the evaluation of testing criteria.”

The most recent update of the American Society of Clinical Oncology and College of American Pathologists (ASCO-CAP) guidelines for interpreting HER2 diagnostic assays affected about 5% of breast cancer patients in three large clinical trials, researchers reported in the Journal of Clinical Oncology.

Although this is “a small minority of patients,” clinical correlates fail to support three of the five groups of patients that the updated guidelines designated based on HER2 FISH [fluorescent in situ hybridization] ratio and average number of HER2 gene copies per tumor cell, said Michael Press, MD, of the University of Southern California Norris Comprehensive Cancer Center, Los Angeles, and his associates.

“Our findings support the original categorizations of HER2 by FISH status in BCIRG [Breast Cancer International Research Group]/Translational Research in Oncology trials,” they said.

The most recent ASCO-CAP guidelines differ from Food and Drug Administration–approved package inserts for HER2 FISH companion diagnostic assays, which reflect the criteria used in clinical trials of the BCIRG/Translational Research in Oncology (TRIO) and previous (2007) ASCO-CAP guidelines, the researchers noted. In particular, the updated guidelines split patients into group 1 (in situ hybridization [ISH] positive, with a HER2-to-chromosome 17 centromere ratio of at least 2.0 and an average of at least four copies of the HER2 gene per tumor cell), group 2 (ISH positive, with a ratio of at least 2.0 and less than four HER2 gene copies), group 3 (ISH positive, with a ratio of less than 2.0 and at least six gene copies), group 4 (ISH equivocal, with a ratio of less than 2.0 and at least four but fewer than six gene copies), and group 5 (ISH negative, a ratio of less than 2.0 and fewer than four gene copies).

The researchers retrospectively analyzed detailed outcomes data from the BCIRG-005, BCIRG- 006, and BCIRG-007 clinical trials, which “now have long-term clinical follow-up data available that facilitate determination of whether the new HER2 guidelines for FISH are clinically useful and predictive of known outcomes,” they said.

The investigators counted cases in each of the five groups and looked to see if these groups correlated with the clinical implications of HER2 gene amplification, such as overexpression of HER2 protein and worse disease-free and overall survival without HER2 targeted therapy (J Clin Oncol. 2016 Aug 29. doi: 10.1200/JCO.2016.66.6693).

Among 10,468 patients in these trials, the vast majority fell into group 1 (41%) or 5 (54%), while 0.7% were in group 2, 0.5% were in group 3, and 4% were in group 4. HER2 amplification status did not change for most patients because the updated guidelines did not affect group 1 (amplified) or group 5 (not amplified). But groups 2 and 4, which the guidelines respectively designated as ISH positive and ISH equivocal, actually seemed to be HER2 not amplified, as neither group was associated with HER2 protein overexpression, group 2 showed a lack of response to trastuzumab therapy, and patients in group 4 who received only chemotherapy had a prognosis similar to that of group 5 in terms of disease-free and overall survival, the researchers reported.

“Overall, we observe approximately 99.3% agreement with initial FDA-approved guidelines and 94.7% agreement with current ASCO-CAP guidelines,” they wrote. “The 4.6% differential is related to only two groups, groups 3 and 4, introduced by ASCO-CAP that lead to different assessments of HER2 status, compared with FDA criteria. Finally, our observations indicate group 2, which represents 0.7% of breast cancers, is misclassified by both the FDA and ASCO-CAP guidelines as amplified and ISH positive.”

They also found that patients in group 3, which the guidelines designated as ISH positive, actually had both HER2 amplified and HER2 not-amplified breast cancers. “There are now nearly 3 decades of accumulated experience and published data studying this alteration in human breast cancers,” the investigators concluded. “Although guidelines are helpful, diagnostic judgment and long-term outcome data remain important in the evaluation of testing criteria.”

BETHESDA, MD. – A novel, peer- and nurse-led intervention in a primary care setting for type 2 diabetes in people with serious mental illness was associated with improvements in depression symptoms, global psychopathology, and overall health, a study has shown.

“The intervention really is patient self-management. It could be a nice complement to team-based, multidisciplinary care,” said Martha Sajatovic, MD, who presented the data in a poster at a National Institute of Mental Health conference on mental health services research. Dr. Sajatovic is the Willard W. Brown Chair and director of the Neurological & Behavioral Outcomes Center at University Hospitals Neurological Institute in Cleveland.

Whitney McKnight/Frontline Medical News

People with serious mental illness (SMI) have a significantly higher risk of premature death than do those in the general population, in part because this cohort experiences higher rates of metabolic disease, often exacerbated by higher rates of smoking, poor diet, substance abuse, and lack of exercise. However, in a 60-week randomized controlled trial of 200 people with SMI and comorbid type 2 diabetes, which was conducted in a primary care setting, those who were taught better self-care fared better than did those who received treatment as usual.

The group-based, psychosocial intervention – called “targeted training in illness” – blended psychoeducation, problem identification, goal setting, behavioral modeling, and care coordination around SMI and diabetes. In the first 12 weeks, groups of 6-10 people met in weekly, hour-long sessions co-led by a peer and nurse educator. Group discussions focused on self-management of diabetes through proper eating habits, regular exercise, tobacco cessation, and other forms of behavior modification.

Meeting as a group helped to “combat some of the social isolation that you see in this population,” Dr. Sajatovic said in an interview. “The peer leadership is really critical, too, because it empowers [the participants]. I believe peer support gives resilience ... and helps [the group] see you don’t have to be perfect to make progress.” In the study, the 3 months of group sessions were followed by weekly telephone maintenance sessions with either the peer or nurse educator for 48 weeks.

Half of the study’s participants – two-thirds of whom were women, and just over half of whom were black – had had a diagnosis of diabetes for at least 10 years; half of all participants used insulin. All had either schizophrenia, schizoaffective disorder, bipolar disorder, or major depressive disorder. Baseline rates of depression were high, and psychotic symptoms were minimal.

After assessments at baseline, 13, 30, and 60 weeks, the study arm was found to have improvements in depression, global psychopathology, and functional status, which Dr. Sajatovic said could be attributable to the group’s significantly improved knowledge about diabetes (P less than .01).

Glycemic control improved generally, a surprising finding that Dr. Sajatovic said could have been tied to the expansion of Medicaid in Ohio, where the study was done, and a “real concerted effort” to provide treatment by medical homes at this time.

While no significant difference between the groups was found overall, a post hoc analysis showed a difference in the 53% of the entire sample who had good to fair glycemic control (hemoglobin A_1c equal to or less than 7.5) at baseline: At 60 weeks, those in the treatment arm achieved stable, long-term control compared with controls, whose values had worsened slightly (P = .024). Those people tended to be older, more likely to have schizophrenia, and less likely to be on insulin, and to have a shorter history of diabetes, said Dr. Sajatovic, professor of psychiatry and of neurology at Case Western Reserve University, Cleveland.

Compared with controls, the study arm had greater improvement at 60 weeks in Clinical Global Impression scores (P = .0008); Montgomery-Åsberg Depression Rating Scale scores (P = .0156); Global Assessment of Functioning scores (P = .0031); and knowledge of diabetes (P less than .0002), as well as an improvement trend in Sheehan Disability Scale scores (P = .0863). There was no difference between the groups on the Brief Psychiatric Rating Scale, the Short Form–36 or HbA_1c values. By study’s end, Dr. Sajatovic said about a quarter had been lost to follow-up.

The intervention meets three important criteria, she said. “First, people need to know what to do. Then, they need to have confidence, or self-efficacy. The third thing is that the person has to believe in a given outcome based on a given behavior.”

Dr. Sajatovic did not have any relevant disclosures. The National Institutes of Health funded the study.

[email protected]

On Twitter @whitneymcknight

BETHESDA, MD. – A novel, peer- and nurse-led intervention in a primary care setting for type 2 diabetes in people with serious mental illness was associated with improvements in depression symptoms, global psychopathology, and overall health, a study has shown.

“The intervention really is patient self-management. It could be a nice complement to team-based, multidisciplinary care,” said Martha Sajatovic, MD, who presented the data in a poster at a National Institute of Mental Health conference on mental health services research. Dr. Sajatovic is the Willard W. Brown Chair and director of the Neurological & Behavioral Outcomes Center at University Hospitals Neurological Institute in Cleveland.

Whitney McKnight/Frontline Medical News

People with serious mental illness (SMI) have a significantly higher risk of premature death than do those in the general population, in part because this cohort experiences higher rates of metabolic disease, often exacerbated by higher rates of smoking, poor diet, substance abuse, and lack of exercise. However, in a 60-week randomized controlled trial of 200 people with SMI and comorbid type 2 diabetes, which was conducted in a primary care setting, those who were taught better self-care fared better than did those who received treatment as usual.

The group-based, psychosocial intervention – called “targeted training in illness” – blended psychoeducation, problem identification, goal setting, behavioral modeling, and care coordination around SMI and diabetes. In the first 12 weeks, groups of 6-10 people met in weekly, hour-long sessions co-led by a peer and nurse educator. Group discussions focused on self-management of diabetes through proper eating habits, regular exercise, tobacco cessation, and other forms of behavior modification.

Meeting as a group helped to “combat some of the social isolation that you see in this population,” Dr. Sajatovic said in an interview. “The peer leadership is really critical, too, because it empowers [the participants]. I believe peer support gives resilience ... and helps [the group] see you don’t have to be perfect to make progress.” In the study, the 3 months of group sessions were followed by weekly telephone maintenance sessions with either the peer or nurse educator for 48 weeks.

Half of the study’s participants – two-thirds of whom were women, and just over half of whom were black – had had a diagnosis of diabetes for at least 10 years; half of all participants used insulin. All had either schizophrenia, schizoaffective disorder, bipolar disorder, or major depressive disorder. Baseline rates of depression were high, and psychotic symptoms were minimal.

After assessments at baseline, 13, 30, and 60 weeks, the study arm was found to have improvements in depression, global psychopathology, and functional status, which Dr. Sajatovic said could be attributable to the group’s significantly improved knowledge about diabetes (P less than .01).

Glycemic control improved generally, a surprising finding that Dr. Sajatovic said could have been tied to the expansion of Medicaid in Ohio, where the study was done, and a “real concerted effort” to provide treatment by medical homes at this time.

While no significant difference between the groups was found overall, a post hoc analysis showed a difference in the 53% of the entire sample who had good to fair glycemic control (hemoglobin A_1c equal to or less than 7.5) at baseline: At 60 weeks, those in the treatment arm achieved stable, long-term control compared with controls, whose values had worsened slightly (P = .024). Those people tended to be older, more likely to have schizophrenia, and less likely to be on insulin, and to have a shorter history of diabetes, said Dr. Sajatovic, professor of psychiatry and of neurology at Case Western Reserve University, Cleveland.

Compared with controls, the study arm had greater improvement at 60 weeks in Clinical Global Impression scores (P = .0008); Montgomery-Åsberg Depression Rating Scale scores (P = .0156); Global Assessment of Functioning scores (P = .0031); and knowledge of diabetes (P less than .0002), as well as an improvement trend in Sheehan Disability Scale scores (P = .0863). There was no difference between the groups on the Brief Psychiatric Rating Scale, the Short Form–36 or HbA_1c values. By study’s end, Dr. Sajatovic said about a quarter had been lost to follow-up.

The intervention meets three important criteria, she said. “First, people need to know what to do. Then, they need to have confidence, or self-efficacy. The third thing is that the person has to believe in a given outcome based on a given behavior.”

Dr. Sajatovic did not have any relevant disclosures. The National Institutes of Health funded the study.

[email protected]

On Twitter @whitneymcknight

BETHESDA, MD. – A novel, peer- and nurse-led intervention in a primary care setting for type 2 diabetes in people with serious mental illness was associated with improvements in depression symptoms, global psychopathology, and overall health, a study has shown.

“The intervention really is patient self-management. It could be a nice complement to team-based, multidisciplinary care,” said Martha Sajatovic, MD, who presented the data in a poster at a National Institute of Mental Health conference on mental health services research. Dr. Sajatovic is the Willard W. Brown Chair and director of the Neurological & Behavioral Outcomes Center at University Hospitals Neurological Institute in Cleveland.

Whitney McKnight/Frontline Medical News

People with serious mental illness (SMI) have a significantly higher risk of premature death than do those in the general population, in part because this cohort experiences higher rates of metabolic disease, often exacerbated by higher rates of smoking, poor diet, substance abuse, and lack of exercise. However, in a 60-week randomized controlled trial of 200 people with SMI and comorbid type 2 diabetes, which was conducted in a primary care setting, those who were taught better self-care fared better than did those who received treatment as usual.

The group-based, psychosocial intervention – called “targeted training in illness” – blended psychoeducation, problem identification, goal setting, behavioral modeling, and care coordination around SMI and diabetes. In the first 12 weeks, groups of 6-10 people met in weekly, hour-long sessions co-led by a peer and nurse educator. Group discussions focused on self-management of diabetes through proper eating habits, regular exercise, tobacco cessation, and other forms of behavior modification.

Meeting as a group helped to “combat some of the social isolation that you see in this population,” Dr. Sajatovic said in an interview. “The peer leadership is really critical, too, because it empowers [the participants]. I believe peer support gives resilience ... and helps [the group] see you don’t have to be perfect to make progress.” In the study, the 3 months of group sessions were followed by weekly telephone maintenance sessions with either the peer or nurse educator for 48 weeks.

Half of the study’s participants – two-thirds of whom were women, and just over half of whom were black – had had a diagnosis of diabetes for at least 10 years; half of all participants used insulin. All had either schizophrenia, schizoaffective disorder, bipolar disorder, or major depressive disorder. Baseline rates of depression were high, and psychotic symptoms were minimal.

After assessments at baseline, 13, 30, and 60 weeks, the study arm was found to have improvements in depression, global psychopathology, and functional status, which Dr. Sajatovic said could be attributable to the group’s significantly improved knowledge about diabetes (P less than .01).

Glycemic control improved generally, a surprising finding that Dr. Sajatovic said could have been tied to the expansion of Medicaid in Ohio, where the study was done, and a “real concerted effort” to provide treatment by medical homes at this time.

While no significant difference between the groups was found overall, a post hoc analysis showed a difference in the 53% of the entire sample who had good to fair glycemic control (hemoglobin A_1c equal to or less than 7.5) at baseline: At 60 weeks, those in the treatment arm achieved stable, long-term control compared with controls, whose values had worsened slightly (P = .024). Those people tended to be older, more likely to have schizophrenia, and less likely to be on insulin, and to have a shorter history of diabetes, said Dr. Sajatovic, professor of psychiatry and of neurology at Case Western Reserve University, Cleveland.

Compared with controls, the study arm had greater improvement at 60 weeks in Clinical Global Impression scores (P = .0008); Montgomery-Åsberg Depression Rating Scale scores (P = .0156); Global Assessment of Functioning scores (P = .0031); and knowledge of diabetes (P less than .0002), as well as an improvement trend in Sheehan Disability Scale scores (P = .0863). There was no difference between the groups on the Brief Psychiatric Rating Scale, the Short Form–36 or HbA_1c values. By study’s end, Dr. Sajatovic said about a quarter had been lost to follow-up.

The intervention meets three important criteria, she said. “First, people need to know what to do. Then, they need to have confidence, or self-efficacy. The third thing is that the person has to believe in a given outcome based on a given behavior.”

Dr. Sajatovic did not have any relevant disclosures. The National Institutes of Health funded the study.

[email protected]

On Twitter @whitneymcknight

Q)

I’ve received mixed messages about whom to screen for chronic kidney disease (CKD). The US Preventive Services Task Force (USPSTF) recommends screening only patients at high risk, but kidney experts advise screening everyone. Who is right? What does the data show?

In 2012, the USPSTF stated that there was insufficient evidence to assess the benefit, or harm, of regularly screening asymptomatic adults for CKD.¹ Other expert medical panels have come to this conclusion as well, and therefore only recommend screening highrisk patients.²

The National Kidney Foundation (NKF) encourages clinicians to assess all patients for risk factors of CKD. Diabetes and hypertension are strongly established risk factors for kidney disease; others include family history of kidney disease; cardiovascular disease; obesity; and older age.

If a patient is at risk for CKD, the NKF recommends testing serum creatinine levels to estimate glomerular filtration rate and testing urine for protein (microalbuminuria or macroalbuminuria). These tests are readily accessible in a primary care setting. It should be noted that one-time testing of serum creatinine and/or urine has not been studied for sensitivity or specificity in the diagnosis of CKD. Diagnosis should be based on decreased renal function or kidney damage occurring over a three-month span.³

In May 2016, Canadian researchers published results from the See Kidney Disease Targeted Screening Program for CKD, comparing CKD screening in the general population with a targeted, at-risk individual population.⁴ The study, which included more than 6,000 participants, revealed a higher rate of unrecognized CKD in the at-risk population than in the general population (21.9% and 14.7%, respectively).

These findings support the idea that screening at-risk patients identifies more cases of CKD than screening the general patient population does.⁴ Early diagnosis of CKD, through recognition of risk factors, provides an opportunity to decrease complications and manage conditions that contribute to the progression of renal disease.^2,3 —RVR

Rebecca V. Rokosky, MSN, APRN, FNP
Renal Associates Clinical Advancement Center in San Antonio, Texas

Q)

I’ve received mixed messages about whom to screen for chronic kidney disease (CKD). The US Preventive Services Task Force (USPSTF) recommends screening only patients at high risk, but kidney experts advise screening everyone. Who is right? What does the data show?

In 2012, the USPSTF stated that there was insufficient evidence to assess the benefit, or harm, of regularly screening asymptomatic adults for CKD.¹ Other expert medical panels have come to this conclusion as well, and therefore only recommend screening highrisk patients.²

The National Kidney Foundation (NKF) encourages clinicians to assess all patients for risk factors of CKD. Diabetes and hypertension are strongly established risk factors for kidney disease; others include family history of kidney disease; cardiovascular disease; obesity; and older age.

If a patient is at risk for CKD, the NKF recommends testing serum creatinine levels to estimate glomerular filtration rate and testing urine for protein (microalbuminuria or macroalbuminuria). These tests are readily accessible in a primary care setting. It should be noted that one-time testing of serum creatinine and/or urine has not been studied for sensitivity or specificity in the diagnosis of CKD. Diagnosis should be based on decreased renal function or kidney damage occurring over a three-month span.³

In May 2016, Canadian researchers published results from the See Kidney Disease Targeted Screening Program for CKD, comparing CKD screening in the general population with a targeted, at-risk individual population.⁴ The study, which included more than 6,000 participants, revealed a higher rate of unrecognized CKD in the at-risk population than in the general population (21.9% and 14.7%, respectively).

These findings support the idea that screening at-risk patients identifies more cases of CKD than screening the general patient population does.⁴ Early diagnosis of CKD, through recognition of risk factors, provides an opportunity to decrease complications and manage conditions that contribute to the progression of renal disease.^2,3 —RVR

Rebecca V. Rokosky, MSN, APRN, FNP
Renal Associates Clinical Advancement Center in San Antonio, Texas

Q)

I’ve received mixed messages about whom to screen for chronic kidney disease (CKD). The US Preventive Services Task Force (USPSTF) recommends screening only patients at high risk, but kidney experts advise screening everyone. Who is right? What does the data show?

In 2012, the USPSTF stated that there was insufficient evidence to assess the benefit, or harm, of regularly screening asymptomatic adults for CKD.¹ Other expert medical panels have come to this conclusion as well, and therefore only recommend screening highrisk patients.²

The National Kidney Foundation (NKF) encourages clinicians to assess all patients for risk factors of CKD. Diabetes and hypertension are strongly established risk factors for kidney disease; others include family history of kidney disease; cardiovascular disease; obesity; and older age.

If a patient is at risk for CKD, the NKF recommends testing serum creatinine levels to estimate glomerular filtration rate and testing urine for protein (microalbuminuria or macroalbuminuria). These tests are readily accessible in a primary care setting. It should be noted that one-time testing of serum creatinine and/or urine has not been studied for sensitivity or specificity in the diagnosis of CKD. Diagnosis should be based on decreased renal function or kidney damage occurring over a three-month span.³

In May 2016, Canadian researchers published results from the See Kidney Disease Targeted Screening Program for CKD, comparing CKD screening in the general population with a targeted, at-risk individual population.⁴ The study, which included more than 6,000 participants, revealed a higher rate of unrecognized CKD in the at-risk population than in the general population (21.9% and 14.7%, respectively).

These findings support the idea that screening at-risk patients identifies more cases of CKD than screening the general patient population does.⁴ Early diagnosis of CKD, through recognition of risk factors, provides an opportunity to decrease complications and manage conditions that contribute to the progression of renal disease.^2,3 —RVR

Rebecca V. Rokosky, MSN, APRN, FNP
Renal Associates Clinical Advancement Center in San Antonio, Texas