Article

To the Editor:

Historically, commonly available antifungal medications have been effective for treating dermatophytosis (tinea). However, recent tinea outbreaks caused by Trichophyton indotineae—a dermatophyte often resistant to terbinafine and sometimes to other antifungals—have been reported in South Asia, Europe, the Middle East, Southeast Asia, and Australia.^1-5

Three confirmed cases of T indotineae dermatophytosis in the United States were reported in 2023 in New York^3,6; a fourth confirmed case was reported in 2024 in Pennsylvania.⁷ Post hoc laboratory testing of fungal isolates in New York in 2022 and 2023 identified an additional 11 cases.⁸ We present a case of extensive multidrug-resistant tinea caused by T indotineae in a man in California.

An otherwise healthy 65-year-old man who had traveled to Europe in the past 3 months presented to his primary care physician with a widespread pruritic rash (Figure 1). He was treated with 2 weeks of oral terbinafine 250 mg/d and topical medicines, including clotrimazole cream 1%, fluocinonide ointment 0.05%, and clobetasol ointment 0.05% without improvement. Subsequently, 2 weeks of oral griseofulvin microsize 500 mg/d also proved ineffective. An antibody test was negative for HIV. His hemoglobin A_1c was 6.2% (reference range, ≤5.6%). The patient was referred to dermatology.

Erythematous plaques—many scaly throughout and some annular with central clearing—were present on the arms, legs, and torso as well as in the groin. Honey crust was present on some plaques on the leg. A potassium hydroxide preparation showed abundant fungal hyphae. Material for fungal and bacterial cultures was collected. The patient was treated again with oral terbinafine 250 mg/d, an oral prednisone taper starting at 60 mg/d for a presumed id reaction, and various oral antihistamines for pruritus; all were ineffective. A bacterial culture showed only mixed skin flora. Oral fluconazole 200 mg/d was prescribed. A skin biopsy specimen showed compact orthokeratosis and parakeratosis of the stratum corneum with few neutrophils and focal pustule formation (Figure 2). Superficial perivascular inflammation, including lymphocytes, histiocytes, and few neutrophils, was present. A periodic acid–Schiff stain showed fungal hyphae in the stratum corneum and a hair follicle (Figure 3). After approximately 2 weeks, mold was identified in the fungal culture. Approximately 2 weeks thereafter, the organism was reported as Trichophyton species.

Acknowledgments—Jeremy Gold, MD; Dallas J. Smith, PharmD; and Shawn Lockhart, PhD, all of the Centers for Disease Control and Prevention, Mycotic Diseases Branch (Atlanta, Georgia), provided helpful comments to the authors in preparing the manuscript of this article.

To the Editor:

Historically, commonly available antifungal medications have been effective for treating dermatophytosis (tinea). However, recent tinea outbreaks caused by Trichophyton indotineae—a dermatophyte often resistant to terbinafine and sometimes to other antifungals—have been reported in South Asia, Europe, the Middle East, Southeast Asia, and Australia.^1-5

Three confirmed cases of T indotineae dermatophytosis in the United States were reported in 2023 in New York^3,6; a fourth confirmed case was reported in 2024 in Pennsylvania.⁷ Post hoc laboratory testing of fungal isolates in New York in 2022 and 2023 identified an additional 11 cases.⁸ We present a case of extensive multidrug-resistant tinea caused by T indotineae in a man in California.

An otherwise healthy 65-year-old man who had traveled to Europe in the past 3 months presented to his primary care physician with a widespread pruritic rash (Figure 1). He was treated with 2 weeks of oral terbinafine 250 mg/d and topical medicines, including clotrimazole cream 1%, fluocinonide ointment 0.05%, and clobetasol ointment 0.05% without improvement. Subsequently, 2 weeks of oral griseofulvin microsize 500 mg/d also proved ineffective. An antibody test was negative for HIV. His hemoglobin A_1c was 6.2% (reference range, ≤5.6%). The patient was referred to dermatology.

Erythematous plaques—many scaly throughout and some annular with central clearing—were present on the arms, legs, and torso as well as in the groin. Honey crust was present on some plaques on the leg. A potassium hydroxide preparation showed abundant fungal hyphae. Material for fungal and bacterial cultures was collected. The patient was treated again with oral terbinafine 250 mg/d, an oral prednisone taper starting at 60 mg/d for a presumed id reaction, and various oral antihistamines for pruritus; all were ineffective. A bacterial culture showed only mixed skin flora. Oral fluconazole 200 mg/d was prescribed. A skin biopsy specimen showed compact orthokeratosis and parakeratosis of the stratum corneum with few neutrophils and focal pustule formation (Figure 2). Superficial perivascular inflammation, including lymphocytes, histiocytes, and few neutrophils, was present. A periodic acid–Schiff stain showed fungal hyphae in the stratum corneum and a hair follicle (Figure 3). After approximately 2 weeks, mold was identified in the fungal culture. Approximately 2 weeks thereafter, the organism was reported as Trichophyton species.

Acknowledgments—Jeremy Gold, MD; Dallas J. Smith, PharmD; and Shawn Lockhart, PhD, all of the Centers for Disease Control and Prevention, Mycotic Diseases Branch (Atlanta, Georgia), provided helpful comments to the authors in preparing the manuscript of this article.

To the Editor:

Historically, commonly available antifungal medications have been effective for treating dermatophytosis (tinea). However, recent tinea outbreaks caused by Trichophyton indotineae—a dermatophyte often resistant to terbinafine and sometimes to other antifungals—have been reported in South Asia, Europe, the Middle East, Southeast Asia, and Australia.^1-5

Three confirmed cases of T indotineae dermatophytosis in the United States were reported in 2023 in New York^3,6; a fourth confirmed case was reported in 2024 in Pennsylvania.⁷ Post hoc laboratory testing of fungal isolates in New York in 2022 and 2023 identified an additional 11 cases.⁸ We present a case of extensive multidrug-resistant tinea caused by T indotineae in a man in California.

An otherwise healthy 65-year-old man who had traveled to Europe in the past 3 months presented to his primary care physician with a widespread pruritic rash (Figure 1). He was treated with 2 weeks of oral terbinafine 250 mg/d and topical medicines, including clotrimazole cream 1%, fluocinonide ointment 0.05%, and clobetasol ointment 0.05% without improvement. Subsequently, 2 weeks of oral griseofulvin microsize 500 mg/d also proved ineffective. An antibody test was negative for HIV. His hemoglobin A_1c was 6.2% (reference range, ≤5.6%). The patient was referred to dermatology.

Erythematous plaques—many scaly throughout and some annular with central clearing—were present on the arms, legs, and torso as well as in the groin. Honey crust was present on some plaques on the leg. A potassium hydroxide preparation showed abundant fungal hyphae. Material for fungal and bacterial cultures was collected. The patient was treated again with oral terbinafine 250 mg/d, an oral prednisone taper starting at 60 mg/d for a presumed id reaction, and various oral antihistamines for pruritus; all were ineffective. A bacterial culture showed only mixed skin flora. Oral fluconazole 200 mg/d was prescribed. A skin biopsy specimen showed compact orthokeratosis and parakeratosis of the stratum corneum with few neutrophils and focal pustule formation (Figure 2). Superficial perivascular inflammation, including lymphocytes, histiocytes, and few neutrophils, was present. A periodic acid–Schiff stain showed fungal hyphae in the stratum corneum and a hair follicle (Figure 3). After approximately 2 weeks, mold was identified in the fungal culture. Approximately 2 weeks thereafter, the organism was reported as Trichophyton species.

Acknowledgments—Jeremy Gold, MD; Dallas J. Smith, PharmD; and Shawn Lockhart, PhD, all of the Centers for Disease Control and Prevention, Mycotic Diseases Branch (Atlanta, Georgia), provided helpful comments to the authors in preparing the manuscript of this article.

Dermatology residents interact with trainees of various levels throughout the workday—from undergraduate or even high school students to postgraduate fellows. Depending on the institution’s training program, residents may have responsibilities to teach through lecture series such as Grand Rounds and didactics. Therefore, it is an integral part of resident training to become educators in addition to being learners; however, formal pedagogy education is rare in dermatology programs. ^1,2 Herein, I discuss several techniques that residents can apply to their practice to cultivate ideal learning environments and outcomes for trainees.

Creating Effective Teaching and Learning Experiences

Planning to teach can be as important as teaching itself. Developing learning objectives can help to create effective teaching and learning experiences. Learning objectives should be specific, time bound, attainable, and learner centered (Table 1). It is recommended that residents aim for no more than 4 objectives per hour of learning.³ By creating clear learning objectives, residents can make connections between the content and any assessments. Bloom’s taxonomy of cognitive learning objectives gives guidance on action verbs to use in writing learning ­objectives depending on the cognitive process being tested (Table 2).⁴

Creating a Safe Educational Environment

Psychological safety is the belief that a learning environment is a safe place in which to take risks.⁵ A clinical learning environment that is psychologically safe can support trainee well-being and learning. Cultivating a safe educational environment may include addressing microaggressions and bias in the clinical workplace. Table 3 provides examples of statements using the 6 Ds, which can be used to mitigate these issues.⁶ The first 4—direct, distract, delegate, and defer—represent ways to respond to racism, microaggressions, and bias, and the last 2—­display discomfort and debrief—are responses that may be ­utilized in any problematic incident. Residents can play an important supportive role in scenarios where learners are faced with an incident that may not be regarded as psychologically safe. This is especially true if the learner is at a lower training level than the dermatology resident. We all play a role in creating a safe workplace for our teams.

Teaching in the Clinic and Hospital

There are multiple challenges to teaching in both inpatient and outpatient environments, including limited space and time; thus, more informal teaching methods are common. For example, in an outpatient dermatology clinic, the patient schedule can become a “table of contents” of potential teaching and learning opportunities. This technique is called the focused half day.^3,7 By reviewing the clinic schedule, students can focus on a specific area of interest or theme throughout the course of the day.³

Priming and framing are other focused techniques that work well in both outpatient and inpatient settings.^3,8,9 Priming means alerting the trainee to upcoming learning objective(s) and focusing their attention on what to observe or do during a shared visit with a patient. Framing—instructing learners to collect information that is relevant to the diagnosis and treatment—allows trainees to help move patient care forward while the resident attends to other patients.³

Modeling involves describing a thought process out loud for a learner^3,10; for example, prior to starting a patient encounter, a dermatology resident may clearly state the goal of a patient conversation to the learner, describe their thought process about the topic, summarize the important points, and ask the learner if they have any questions about what was just said. Using this technique, learners may have a better understanding of why and how to go about conducting a patient encounter after the resident models one for them.

Effectively Integrating Visual Media and Presentations

Research supported by the cognitive load theory and cognitive theory of multimedia learning has led to the assertion-evidence approach for creating presentation slides that are built around messages, not topics, and messages are supported with visuals, not bullets.^3,11,12 For example, slides should be constructed with 1- to 2-line assertion statements as titles and relevant illustrations or figures as supporting evidence to enhance visual memory.³

Written text on presentation slides often is redundant with spoken narration and also decreases learning because of cognitive load. Busy background colors and/or designs consume working memory and also can be detrimental to learning. Limiting these common distractors in a presentation makes for more effective delivery and retention of knowledge.³

Final Thoughts

There are multiple avenues for teaching as a resident and not all techniques may be applicable depending on the clinical or academic scenario. This column provides a starting point for residents to augment their pedagogical skills, particularly because formal teaching on pedagogy is lacking in medical education.

Dermatology residents interact with trainees of various levels throughout the workday—from undergraduate or even high school students to postgraduate fellows. Depending on the institution’s training program, residents may have responsibilities to teach through lecture series such as Grand Rounds and didactics. Therefore, it is an integral part of resident training to become educators in addition to being learners; however, formal pedagogy education is rare in dermatology programs. ^1,2 Herein, I discuss several techniques that residents can apply to their practice to cultivate ideal learning environments and outcomes for trainees.

Creating Effective Teaching and Learning Experiences

Planning to teach can be as important as teaching itself. Developing learning objectives can help to create effective teaching and learning experiences. Learning objectives should be specific, time bound, attainable, and learner centered (Table 1). It is recommended that residents aim for no more than 4 objectives per hour of learning.³ By creating clear learning objectives, residents can make connections between the content and any assessments. Bloom’s taxonomy of cognitive learning objectives gives guidance on action verbs to use in writing learning ­objectives depending on the cognitive process being tested (Table 2).⁴

Creating a Safe Educational Environment

Psychological safety is the belief that a learning environment is a safe place in which to take risks.⁵ A clinical learning environment that is psychologically safe can support trainee well-being and learning. Cultivating a safe educational environment may include addressing microaggressions and bias in the clinical workplace. Table 3 provides examples of statements using the 6 Ds, which can be used to mitigate these issues.⁶ The first 4—direct, distract, delegate, and defer—represent ways to respond to racism, microaggressions, and bias, and the last 2—­display discomfort and debrief—are responses that may be ­utilized in any problematic incident. Residents can play an important supportive role in scenarios where learners are faced with an incident that may not be regarded as psychologically safe. This is especially true if the learner is at a lower training level than the dermatology resident. We all play a role in creating a safe workplace for our teams.

Teaching in the Clinic and Hospital

There are multiple challenges to teaching in both inpatient and outpatient environments, including limited space and time; thus, more informal teaching methods are common. For example, in an outpatient dermatology clinic, the patient schedule can become a “table of contents” of potential teaching and learning opportunities. This technique is called the focused half day.^3,7 By reviewing the clinic schedule, students can focus on a specific area of interest or theme throughout the course of the day.³

Priming and framing are other focused techniques that work well in both outpatient and inpatient settings.^3,8,9 Priming means alerting the trainee to upcoming learning objective(s) and focusing their attention on what to observe or do during a shared visit with a patient. Framing—instructing learners to collect information that is relevant to the diagnosis and treatment—allows trainees to help move patient care forward while the resident attends to other patients.³

Modeling involves describing a thought process out loud for a learner^3,10; for example, prior to starting a patient encounter, a dermatology resident may clearly state the goal of a patient conversation to the learner, describe their thought process about the topic, summarize the important points, and ask the learner if they have any questions about what was just said. Using this technique, learners may have a better understanding of why and how to go about conducting a patient encounter after the resident models one for them.

Effectively Integrating Visual Media and Presentations

Research supported by the cognitive load theory and cognitive theory of multimedia learning has led to the assertion-evidence approach for creating presentation slides that are built around messages, not topics, and messages are supported with visuals, not bullets.^3,11,12 For example, slides should be constructed with 1- to 2-line assertion statements as titles and relevant illustrations or figures as supporting evidence to enhance visual memory.³

Written text on presentation slides often is redundant with spoken narration and also decreases learning because of cognitive load. Busy background colors and/or designs consume working memory and also can be detrimental to learning. Limiting these common distractors in a presentation makes for more effective delivery and retention of knowledge.³

Final Thoughts

There are multiple avenues for teaching as a resident and not all techniques may be applicable depending on the clinical or academic scenario. This column provides a starting point for residents to augment their pedagogical skills, particularly because formal teaching on pedagogy is lacking in medical education.

Dermatology residents interact with trainees of various levels throughout the workday—from undergraduate or even high school students to postgraduate fellows. Depending on the institution’s training program, residents may have responsibilities to teach through lecture series such as Grand Rounds and didactics. Therefore, it is an integral part of resident training to become educators in addition to being learners; however, formal pedagogy education is rare in dermatology programs. ^1,2 Herein, I discuss several techniques that residents can apply to their practice to cultivate ideal learning environments and outcomes for trainees.

Creating Effective Teaching and Learning Experiences

Planning to teach can be as important as teaching itself. Developing learning objectives can help to create effective teaching and learning experiences. Learning objectives should be specific, time bound, attainable, and learner centered (Table 1). It is recommended that residents aim for no more than 4 objectives per hour of learning.³ By creating clear learning objectives, residents can make connections between the content and any assessments. Bloom’s taxonomy of cognitive learning objectives gives guidance on action verbs to use in writing learning ­objectives depending on the cognitive process being tested (Table 2).⁴

Creating a Safe Educational Environment

Psychological safety is the belief that a learning environment is a safe place in which to take risks.⁵ A clinical learning environment that is psychologically safe can support trainee well-being and learning. Cultivating a safe educational environment may include addressing microaggressions and bias in the clinical workplace. Table 3 provides examples of statements using the 6 Ds, which can be used to mitigate these issues.⁶ The first 4—direct, distract, delegate, and defer—represent ways to respond to racism, microaggressions, and bias, and the last 2—­display discomfort and debrief—are responses that may be ­utilized in any problematic incident. Residents can play an important supportive role in scenarios where learners are faced with an incident that may not be regarded as psychologically safe. This is especially true if the learner is at a lower training level than the dermatology resident. We all play a role in creating a safe workplace for our teams.

Teaching in the Clinic and Hospital

There are multiple challenges to teaching in both inpatient and outpatient environments, including limited space and time; thus, more informal teaching methods are common. For example, in an outpatient dermatology clinic, the patient schedule can become a “table of contents” of potential teaching and learning opportunities. This technique is called the focused half day.^3,7 By reviewing the clinic schedule, students can focus on a specific area of interest or theme throughout the course of the day.³

Priming and framing are other focused techniques that work well in both outpatient and inpatient settings.^3,8,9 Priming means alerting the trainee to upcoming learning objective(s) and focusing their attention on what to observe or do during a shared visit with a patient. Framing—instructing learners to collect information that is relevant to the diagnosis and treatment—allows trainees to help move patient care forward while the resident attends to other patients.³

Modeling involves describing a thought process out loud for a learner^3,10; for example, prior to starting a patient encounter, a dermatology resident may clearly state the goal of a patient conversation to the learner, describe their thought process about the topic, summarize the important points, and ask the learner if they have any questions about what was just said. Using this technique, learners may have a better understanding of why and how to go about conducting a patient encounter after the resident models one for them.

Effectively Integrating Visual Media and Presentations

Research supported by the cognitive load theory and cognitive theory of multimedia learning has led to the assertion-evidence approach for creating presentation slides that are built around messages, not topics, and messages are supported with visuals, not bullets.^3,11,12 For example, slides should be constructed with 1- to 2-line assertion statements as titles and relevant illustrations or figures as supporting evidence to enhance visual memory.³

Written text on presentation slides often is redundant with spoken narration and also decreases learning because of cognitive load. Busy background colors and/or designs consume working memory and also can be detrimental to learning. Limiting these common distractors in a presentation makes for more effective delivery and retention of knowledge.³

Final Thoughts

There are multiple avenues for teaching as a resident and not all techniques may be applicable depending on the clinical or academic scenario. This column provides a starting point for residents to augment their pedagogical skills, particularly because formal teaching on pedagogy is lacking in medical education.

Data have shown that CD20-expressing B cells are crucial to the pathogenesis of multiple sclerosis (MS). First approved by the US Food and Drug Administration for MS in 2017, anti-CD20 monoclonal antibody therapies including ocrelizumab, ofatumumab, and ublituximab have proven effective at controlling the symptoms of relapsing-remitting MS (RRMS).

In this ReCAP, Dr Fred D. Lublin, of the Mount Sinai School of Medicine, discusses recent data on anti-CD20 agents for RRMS, including results presented at the 2024 meeting of the Consortium of Multiple Sclerosis Centers (CMSC).

He discusses a protocol examining the effect on RRMS of extending dosage intervals or stopping anti-CD20 therapy after 1 or 2 years of treatment based on results suggesting that the B cells that return post depletion are predominantly regulatory rather than pathogenic.

Next, Dr Lublin discusses a paper presented at CMSC on risks for serious infections in individuals taking ocrelizumab or ofatumumab. Major predictors were found to be progressive disease, prior use of a disease-modifying therapy, and longer duration of therapy.

Finally, he considers recent studies comparing rituximab, an anti-CD20 therapy not approved for MS in the United States but commonly used off-label internationally, with more recent therapies such as ocrelizumab. Data currently indicate that an increased risk for infections are associated with rituximab vs ocrelizumab, but further research is under way.

--

Fred D. Lublin, MD, Director, The Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Icahn School of Medicine at Mount Sinai, New York, NY

Fred D. Lublin, MD, has disclosed the following relevant financial relationships:

Sources of Funding for Research: Novartis; Biogen; Sanofi; NMSS; NIH; Brainstorm Cell Therapeutics

Consulting Agreements/Advisory Boards/DSMB: Biogen; EMD Serono; Novartis; Actelion/Janssen; Sanofi/Genzyme; Roche/Genentech; Horizon Therapeutics/Amgen; Bristol Myers Squibb; Mapi Pharma; Brainstorm Cell Therapeutics; Mylan/Viatris; Immunic; Avotres; Neurogene; LabCorp; Entelexo Biotherapeutics; Neuralight; SetPoint Medical; Hexal/Sandoz; Baim Institute; Sudo Biosciences; Lapix Therapeutics; Biohaven Pharmaceuticals; Abata Therapeutics; Cognito Therapeutics; ImmPACT Bio

Speaker: Sanofi

Stock Options: Avotres; Neuralight; Lapix Therapeutics; Entelexo

I may discuss unapproved agents that are in the MS developmental pipeline without any recommendation on their use.

Data have shown that CD20-expressing B cells are crucial to the pathogenesis of multiple sclerosis (MS). First approved by the US Food and Drug Administration for MS in 2017, anti-CD20 monoclonal antibody therapies including ocrelizumab, ofatumumab, and ublituximab have proven effective at controlling the symptoms of relapsing-remitting MS (RRMS).

In this ReCAP, Dr Fred D. Lublin, of the Mount Sinai School of Medicine, discusses recent data on anti-CD20 agents for RRMS, including results presented at the 2024 meeting of the Consortium of Multiple Sclerosis Centers (CMSC).

He discusses a protocol examining the effect on RRMS of extending dosage intervals or stopping anti-CD20 therapy after 1 or 2 years of treatment based on results suggesting that the B cells that return post depletion are predominantly regulatory rather than pathogenic.

Next, Dr Lublin discusses a paper presented at CMSC on risks for serious infections in individuals taking ocrelizumab or ofatumumab. Major predictors were found to be progressive disease, prior use of a disease-modifying therapy, and longer duration of therapy.

Finally, he considers recent studies comparing rituximab, an anti-CD20 therapy not approved for MS in the United States but commonly used off-label internationally, with more recent therapies such as ocrelizumab. Data currently indicate that an increased risk for infections are associated with rituximab vs ocrelizumab, but further research is under way.

--

Fred D. Lublin, MD, Director, The Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Icahn School of Medicine at Mount Sinai, New York, NY

Fred D. Lublin, MD, has disclosed the following relevant financial relationships:

Sources of Funding for Research: Novartis; Biogen; Sanofi; NMSS; NIH; Brainstorm Cell Therapeutics

Consulting Agreements/Advisory Boards/DSMB: Biogen; EMD Serono; Novartis; Actelion/Janssen; Sanofi/Genzyme; Roche/Genentech; Horizon Therapeutics/Amgen; Bristol Myers Squibb; Mapi Pharma; Brainstorm Cell Therapeutics; Mylan/Viatris; Immunic; Avotres; Neurogene; LabCorp; Entelexo Biotherapeutics; Neuralight; SetPoint Medical; Hexal/Sandoz; Baim Institute; Sudo Biosciences; Lapix Therapeutics; Biohaven Pharmaceuticals; Abata Therapeutics; Cognito Therapeutics; ImmPACT Bio

Speaker: Sanofi

Stock Options: Avotres; Neuralight; Lapix Therapeutics; Entelexo

I may discuss unapproved agents that are in the MS developmental pipeline without any recommendation on their use.

Data have shown that CD20-expressing B cells are crucial to the pathogenesis of multiple sclerosis (MS). First approved by the US Food and Drug Administration for MS in 2017, anti-CD20 monoclonal antibody therapies including ocrelizumab, ofatumumab, and ublituximab have proven effective at controlling the symptoms of relapsing-remitting MS (RRMS).

In this ReCAP, Dr Fred D. Lublin, of the Mount Sinai School of Medicine, discusses recent data on anti-CD20 agents for RRMS, including results presented at the 2024 meeting of the Consortium of Multiple Sclerosis Centers (CMSC).

He discusses a protocol examining the effect on RRMS of extending dosage intervals or stopping anti-CD20 therapy after 1 or 2 years of treatment based on results suggesting that the B cells that return post depletion are predominantly regulatory rather than pathogenic.

Next, Dr Lublin discusses a paper presented at CMSC on risks for serious infections in individuals taking ocrelizumab or ofatumumab. Major predictors were found to be progressive disease, prior use of a disease-modifying therapy, and longer duration of therapy.

Finally, he considers recent studies comparing rituximab, an anti-CD20 therapy not approved for MS in the United States but commonly used off-label internationally, with more recent therapies such as ocrelizumab. Data currently indicate that an increased risk for infections are associated with rituximab vs ocrelizumab, but further research is under way.

--

Fred D. Lublin, MD, Director, The Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Icahn School of Medicine at Mount Sinai, New York, NY

Fred D. Lublin, MD, has disclosed the following relevant financial relationships:

Sources of Funding for Research: Novartis; Biogen; Sanofi; NMSS; NIH; Brainstorm Cell Therapeutics

Consulting Agreements/Advisory Boards/DSMB: Biogen; EMD Serono; Novartis; Actelion/Janssen; Sanofi/Genzyme; Roche/Genentech; Horizon Therapeutics/Amgen; Bristol Myers Squibb; Mapi Pharma; Brainstorm Cell Therapeutics; Mylan/Viatris; Immunic; Avotres; Neurogene; LabCorp; Entelexo Biotherapeutics; Neuralight; SetPoint Medical; Hexal/Sandoz; Baim Institute; Sudo Biosciences; Lapix Therapeutics; Biohaven Pharmaceuticals; Abata Therapeutics; Cognito Therapeutics; ImmPACT Bio

Speaker: Sanofi

Stock Options: Avotres; Neuralight; Lapix Therapeutics; Entelexo

I may discuss unapproved agents that are in the MS developmental pipeline without any recommendation on their use.

To the Editor:

Cardiac rhabdomyomas are benign hamartomas that are common in patients with tuberous sclerosis complex (TSC).¹ We describe a patient who presented with large infantile hemangiomas (IHs) and hypopigmented macules, which prompted further testing that eventually showed concomitant multiple cardiac rhabdomyomas in the context of TSC.

A 5-week-old girl—who was born at 38 weeks and 3 days’ gestation via uncomplicated vaginal delivery—was referred to our pediatric dermatology clinic for evaluation of multiple erythematous lesions on the scalp and left buttock that were first noticed 2 weeks prior to presentation. There was a family history of seizures in the patient’s mother. The patient’s older brother did not have similar symptoms.

Physical examination revealed 2 nonulcerating erythematous nodules on the middle and posterior left vertex scalp that measured 2.5×2 cm (Figure 1A) as well as 1 bright red plaque on the left buttock (Figure 1B). Five hypopigmented macules, ranging from 5 mm to 1.5 cm in diameter, also were detected on the left thorax (Figure 2A) as well as the middle and lower back (Figure 2B). These findings, along with the history of seizures in the patient’s mother, prompted further evaluation of the family history, which uncovered TSC in the patient’s mother, maternal aunt, and maternal grandmother.

The large IHs on the scalp did not pose concerns for potential functional impairment but were still considered high risk for permanent alopecia based on clinical practice guidelines for the management of IH.² Treatment with oral propranolol was recommended; however, because of a strong suspicion of TSC due to the presence of 5 hypopigmented macules measuring more than 5 mm in diameter (≥3 hypopigmented macules of ≥5 mm is one of the major criterion for TSC), the patient was referred to cardiology prior to initiation of propranolol.

Echocardiography revealed 3 intracardiac masses measuring 4 to 5 mm in diameter in the left ventricle (LV), along the interventricular septum and the LV posterior wall. These masses were consistent with rhabdomyomas (Figure 3)—a major criterion for TSC—which had not been detected by prenatal ultrasonography. No obstruction to LV inflow or outflow was observed. Additionally, no arrhythmias were detected on electrocardiography.

The patient was cleared for propranolol, which was slowly uptitrated to 2 mg/kg/d. She completed the course without adverse effects. The treatment of IH was successful with substantial reduction in size over the following months until clearance. She also was referred to neurology for magnetic resonance imaging of the brain, which showed a 3-mm subependymal nodule in the lateral right ventricle, another major feature of TSC.

Cardiac rhabdomyomas are benign hamartomas that affect as many as 80% of patients with TSC¹ and are primarily localized in the ventricles. Although cardiac rhabdomyomas usually regress over time, they can compromise ventricular function or valvular function, or both, and result in outflow obstruction, arrhythmias, and Wolff- Parkinson-White syndrome.³ Surgical resection may be needed in patients whose condition is refractory to medical management for heart failure.

The pathophysiologic mechanism behind the natural involution of cardiac rhabdomyomas has not been fully elucidated. It has been hypothesized that these masses stem from the inability of rhabdomyoma cells to divide after birth due to their embryonic myocyte derivation.⁴

According to the TSC diagnostic criteria from the Tuberous Sclerosis Complex International Consensus Group, at least 2 major features or 1 major and 2 minor features are required to make a definitive diagnosis of TSC. Cutaneous signs represent more than one-third of major features of TSC; almost all patients with TSC have skin findings.⁵

Identification of pathogenic mutations in either TSC¹ (on chromosome 9q34.3, encoding for hamartin) or TSC² (on chromosome 16p13.3, encoding for tuberin), resulting in constitutive activation of mammalian target of rapamycin and subsequent increased cell growth, is sufficient for a definitive diagnosis of TSC. However, mutations cannot be identified by conventional genetic testing in as many as one-quarter of patients with TSC; therefore, a negative result does not exclude TSC if the patient meets clinical diagnostic criteria.

Although a cardiology workup is indicated prior to initiating propranolol in the presence of possible cardiac rhabdomyomas, most of those lesions are hemodynamically stable and do not require treatment. There also is no contraindication for β-blocker therapy. In fact, propranolol has been reported as a successful treatment in rhabdomyoma-associated arrhythmias in children.⁶ Notably, obstructive cardiac rhabdomyomas have been successfully treated with mammalian target of rapamycin inhibitors, such as sirolimus⁷ and everolimus.⁸

Baseline cardiology screening with echocardiography prior to initiating propranolol for treatment of IH is not routinely indicated in babies with uncomplicated IH. However, in a patient with TSC, cardiology screening is necessary to rule out rhabdomyomas with associated arrhythmias or obstructed blood flow, or both, prior to initiating treatment.

We presented a case of concomitant IH and TSC in a patient with cardiac rhabdomyomas. The manifestation of large IHs in our patient prompted further testing that revealed multiple cardiac rhabdomyomas in the context of TSC. It is imperative for cardiologists, cardiac surgeons, and dermatologists to be familiar with the TSC diagnostic criteria so that they can reach a prompt diagnosis and make appropriate referrals for further evaluation of cardiac, neurologic, and ophthalmologic signs.

To the Editor:

Cardiac rhabdomyomas are benign hamartomas that are common in patients with tuberous sclerosis complex (TSC).¹ We describe a patient who presented with large infantile hemangiomas (IHs) and hypopigmented macules, which prompted further testing that eventually showed concomitant multiple cardiac rhabdomyomas in the context of TSC.

A 5-week-old girl—who was born at 38 weeks and 3 days’ gestation via uncomplicated vaginal delivery—was referred to our pediatric dermatology clinic for evaluation of multiple erythematous lesions on the scalp and left buttock that were first noticed 2 weeks prior to presentation. There was a family history of seizures in the patient’s mother. The patient’s older brother did not have similar symptoms.

Physical examination revealed 2 nonulcerating erythematous nodules on the middle and posterior left vertex scalp that measured 2.5×2 cm (Figure 1A) as well as 1 bright red plaque on the left buttock (Figure 1B). Five hypopigmented macules, ranging from 5 mm to 1.5 cm in diameter, also were detected on the left thorax (Figure 2A) as well as the middle and lower back (Figure 2B). These findings, along with the history of seizures in the patient’s mother, prompted further evaluation of the family history, which uncovered TSC in the patient’s mother, maternal aunt, and maternal grandmother.

The large IHs on the scalp did not pose concerns for potential functional impairment but were still considered high risk for permanent alopecia based on clinical practice guidelines for the management of IH.² Treatment with oral propranolol was recommended; however, because of a strong suspicion of TSC due to the presence of 5 hypopigmented macules measuring more than 5 mm in diameter (≥3 hypopigmented macules of ≥5 mm is one of the major criterion for TSC), the patient was referred to cardiology prior to initiation of propranolol.

Echocardiography revealed 3 intracardiac masses measuring 4 to 5 mm in diameter in the left ventricle (LV), along the interventricular septum and the LV posterior wall. These masses were consistent with rhabdomyomas (Figure 3)—a major criterion for TSC—which had not been detected by prenatal ultrasonography. No obstruction to LV inflow or outflow was observed. Additionally, no arrhythmias were detected on electrocardiography.

The patient was cleared for propranolol, which was slowly uptitrated to 2 mg/kg/d. She completed the course without adverse effects. The treatment of IH was successful with substantial reduction in size over the following months until clearance. She also was referred to neurology for magnetic resonance imaging of the brain, which showed a 3-mm subependymal nodule in the lateral right ventricle, another major feature of TSC.

Cardiac rhabdomyomas are benign hamartomas that affect as many as 80% of patients with TSC¹ and are primarily localized in the ventricles. Although cardiac rhabdomyomas usually regress over time, they can compromise ventricular function or valvular function, or both, and result in outflow obstruction, arrhythmias, and Wolff- Parkinson-White syndrome.³ Surgical resection may be needed in patients whose condition is refractory to medical management for heart failure.

The pathophysiologic mechanism behind the natural involution of cardiac rhabdomyomas has not been fully elucidated. It has been hypothesized that these masses stem from the inability of rhabdomyoma cells to divide after birth due to their embryonic myocyte derivation.⁴

According to the TSC diagnostic criteria from the Tuberous Sclerosis Complex International Consensus Group, at least 2 major features or 1 major and 2 minor features are required to make a definitive diagnosis of TSC. Cutaneous signs represent more than one-third of major features of TSC; almost all patients with TSC have skin findings.⁵

Identification of pathogenic mutations in either TSC¹ (on chromosome 9q34.3, encoding for hamartin) or TSC² (on chromosome 16p13.3, encoding for tuberin), resulting in constitutive activation of mammalian target of rapamycin and subsequent increased cell growth, is sufficient for a definitive diagnosis of TSC. However, mutations cannot be identified by conventional genetic testing in as many as one-quarter of patients with TSC; therefore, a negative result does not exclude TSC if the patient meets clinical diagnostic criteria.

Although a cardiology workup is indicated prior to initiating propranolol in the presence of possible cardiac rhabdomyomas, most of those lesions are hemodynamically stable and do not require treatment. There also is no contraindication for β-blocker therapy. In fact, propranolol has been reported as a successful treatment in rhabdomyoma-associated arrhythmias in children.⁶ Notably, obstructive cardiac rhabdomyomas have been successfully treated with mammalian target of rapamycin inhibitors, such as sirolimus⁷ and everolimus.⁸

Baseline cardiology screening with echocardiography prior to initiating propranolol for treatment of IH is not routinely indicated in babies with uncomplicated IH. However, in a patient with TSC, cardiology screening is necessary to rule out rhabdomyomas with associated arrhythmias or obstructed blood flow, or both, prior to initiating treatment.

We presented a case of concomitant IH and TSC in a patient with cardiac rhabdomyomas. The manifestation of large IHs in our patient prompted further testing that revealed multiple cardiac rhabdomyomas in the context of TSC. It is imperative for cardiologists, cardiac surgeons, and dermatologists to be familiar with the TSC diagnostic criteria so that they can reach a prompt diagnosis and make appropriate referrals for further evaluation of cardiac, neurologic, and ophthalmologic signs.

To the Editor:

Cardiac rhabdomyomas are benign hamartomas that are common in patients with tuberous sclerosis complex (TSC).¹ We describe a patient who presented with large infantile hemangiomas (IHs) and hypopigmented macules, which prompted further testing that eventually showed concomitant multiple cardiac rhabdomyomas in the context of TSC.

A 5-week-old girl—who was born at 38 weeks and 3 days’ gestation via uncomplicated vaginal delivery—was referred to our pediatric dermatology clinic for evaluation of multiple erythematous lesions on the scalp and left buttock that were first noticed 2 weeks prior to presentation. There was a family history of seizures in the patient’s mother. The patient’s older brother did not have similar symptoms.

Physical examination revealed 2 nonulcerating erythematous nodules on the middle and posterior left vertex scalp that measured 2.5×2 cm (Figure 1A) as well as 1 bright red plaque on the left buttock (Figure 1B). Five hypopigmented macules, ranging from 5 mm to 1.5 cm in diameter, also were detected on the left thorax (Figure 2A) as well as the middle and lower back (Figure 2B). These findings, along with the history of seizures in the patient’s mother, prompted further evaluation of the family history, which uncovered TSC in the patient’s mother, maternal aunt, and maternal grandmother.

The large IHs on the scalp did not pose concerns for potential functional impairment but were still considered high risk for permanent alopecia based on clinical practice guidelines for the management of IH.² Treatment with oral propranolol was recommended; however, because of a strong suspicion of TSC due to the presence of 5 hypopigmented macules measuring more than 5 mm in diameter (≥3 hypopigmented macules of ≥5 mm is one of the major criterion for TSC), the patient was referred to cardiology prior to initiation of propranolol.

Echocardiography revealed 3 intracardiac masses measuring 4 to 5 mm in diameter in the left ventricle (LV), along the interventricular septum and the LV posterior wall. These masses were consistent with rhabdomyomas (Figure 3)—a major criterion for TSC—which had not been detected by prenatal ultrasonography. No obstruction to LV inflow or outflow was observed. Additionally, no arrhythmias were detected on electrocardiography.

The patient was cleared for propranolol, which was slowly uptitrated to 2 mg/kg/d. She completed the course without adverse effects. The treatment of IH was successful with substantial reduction in size over the following months until clearance. She also was referred to neurology for magnetic resonance imaging of the brain, which showed a 3-mm subependymal nodule in the lateral right ventricle, another major feature of TSC.

Cardiac rhabdomyomas are benign hamartomas that affect as many as 80% of patients with TSC¹ and are primarily localized in the ventricles. Although cardiac rhabdomyomas usually regress over time, they can compromise ventricular function or valvular function, or both, and result in outflow obstruction, arrhythmias, and Wolff- Parkinson-White syndrome.³ Surgical resection may be needed in patients whose condition is refractory to medical management for heart failure.

The pathophysiologic mechanism behind the natural involution of cardiac rhabdomyomas has not been fully elucidated. It has been hypothesized that these masses stem from the inability of rhabdomyoma cells to divide after birth due to their embryonic myocyte derivation.⁴

According to the TSC diagnostic criteria from the Tuberous Sclerosis Complex International Consensus Group, at least 2 major features or 1 major and 2 minor features are required to make a definitive diagnosis of TSC. Cutaneous signs represent more than one-third of major features of TSC; almost all patients with TSC have skin findings.⁵

Identification of pathogenic mutations in either TSC¹ (on chromosome 9q34.3, encoding for hamartin) or TSC² (on chromosome 16p13.3, encoding for tuberin), resulting in constitutive activation of mammalian target of rapamycin and subsequent increased cell growth, is sufficient for a definitive diagnosis of TSC. However, mutations cannot be identified by conventional genetic testing in as many as one-quarter of patients with TSC; therefore, a negative result does not exclude TSC if the patient meets clinical diagnostic criteria.

Although a cardiology workup is indicated prior to initiating propranolol in the presence of possible cardiac rhabdomyomas, most of those lesions are hemodynamically stable and do not require treatment. There also is no contraindication for β-blocker therapy. In fact, propranolol has been reported as a successful treatment in rhabdomyoma-associated arrhythmias in children.⁶ Notably, obstructive cardiac rhabdomyomas have been successfully treated with mammalian target of rapamycin inhibitors, such as sirolimus⁷ and everolimus.⁸

Baseline cardiology screening with echocardiography prior to initiating propranolol for treatment of IH is not routinely indicated in babies with uncomplicated IH. However, in a patient with TSC, cardiology screening is necessary to rule out rhabdomyomas with associated arrhythmias or obstructed blood flow, or both, prior to initiating treatment.

We presented a case of concomitant IH and TSC in a patient with cardiac rhabdomyomas. The manifestation of large IHs in our patient prompted further testing that revealed multiple cardiac rhabdomyomas in the context of TSC. It is imperative for cardiologists, cardiac surgeons, and dermatologists to be familiar with the TSC diagnostic criteria so that they can reach a prompt diagnosis and make appropriate referrals for further evaluation of cardiac, neurologic, and ophthalmologic signs.

Nonradiographic axial spondyloarthritis (nr-axSpA) shares many characteristics with radiographic disease and responds to the same treatments, yet it has fewer FDA-approved options.

As Dr Marina Magrey, from Case Western Reserve University School of Medicine, in Cleveland, Ohio, explains, the TNF inhibitor certolizumab has been approved on the basis of results from the C-axSpAnd study.

Similarly, the IL-17 inhibitors secukinumab and ixekizumab are also options, and the results of the COAST-X and PREVENT studies show them to be safe and efficacious.

In closing, Dr Magrey outlines the SELECT-AXIS 2 study showing benefit from the JAK inhibitor upadacitinib for nr-axSpA, with no additional safety signals.

--

Professor of Rheumatology, Case Western Reserve University School of Medicine; Chief, Division of Rheumatology, University Hospitals, Cleveland, Ohio

Marina N. Magrey, MD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Novartis; AbbVie; UCB Pharma; Pfizer; Eli Lilly; Janssen; Bristol Myers Squibb

Received research grant from: AbbVie; Bristol Myers Squibb; Amgen

Nonradiographic axial spondyloarthritis (nr-axSpA) shares many characteristics with radiographic disease and responds to the same treatments, yet it has fewer FDA-approved options.

As Dr Marina Magrey, from Case Western Reserve University School of Medicine, in Cleveland, Ohio, explains, the TNF inhibitor certolizumab has been approved on the basis of results from the C-axSpAnd study.

Similarly, the IL-17 inhibitors secukinumab and ixekizumab are also options, and the results of the COAST-X and PREVENT studies show them to be safe and efficacious.

In closing, Dr Magrey outlines the SELECT-AXIS 2 study showing benefit from the JAK inhibitor upadacitinib for nr-axSpA, with no additional safety signals.

--

Professor of Rheumatology, Case Western Reserve University School of Medicine; Chief, Division of Rheumatology, University Hospitals, Cleveland, Ohio

Marina N. Magrey, MD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Novartis; AbbVie; UCB Pharma; Pfizer; Eli Lilly; Janssen; Bristol Myers Squibb

Received research grant from: AbbVie; Bristol Myers Squibb; Amgen

Nonradiographic axial spondyloarthritis (nr-axSpA) shares many characteristics with radiographic disease and responds to the same treatments, yet it has fewer FDA-approved options.

As Dr Marina Magrey, from Case Western Reserve University School of Medicine, in Cleveland, Ohio, explains, the TNF inhibitor certolizumab has been approved on the basis of results from the C-axSpAnd study.

Similarly, the IL-17 inhibitors secukinumab and ixekizumab are also options, and the results of the COAST-X and PREVENT studies show them to be safe and efficacious.

In closing, Dr Magrey outlines the SELECT-AXIS 2 study showing benefit from the JAK inhibitor upadacitinib for nr-axSpA, with no additional safety signals.

--

Professor of Rheumatology, Case Western Reserve University School of Medicine; Chief, Division of Rheumatology, University Hospitals, Cleveland, Ohio

Marina N. Magrey, MD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Novartis; AbbVie; UCB Pharma; Pfizer; Eli Lilly; Janssen; Bristol Myers Squibb

Received research grant from: AbbVie; Bristol Myers Squibb; Amgen

Overall, persons with schizophrenia are more likely than the general population to be overweight and have cardiovascular risk factors before starting treatment with antipsychotics, and such treatment generally worsens these measures. Weight gain and associated morbidity and mortality are common side effects of antipsychotic medications. Olanzapine is associated with significant weight gain of 7% or more, higher than other second-generation antipsychotics. Olanzapine treatment is the major contributor to this patient's additional weight gain over the past 2 years. This added weight has translated to excess wear and tear on her joints, leading to evidence of osteoarthritis. Treatment with olanzapine is also independently associated with detrimental changes in cardiometabolic parameters.

Interventions to prevent or mitigate weight gain with antipsychotics are limited. In general, the American Psychiatric Association does not recommend switching antipsychotics for patients whose schizophrenia is well managed. However, there is increasing evidence that metformin may have a role in mitigating weight gain as well as beneficially modifying cardiometabolic factors in patients with schizophrenia being treated with olanzapine. A systematic review of emerging evidence with metformin in patients with schizophrenia suggests that metformin may also improve some cognitive symptoms of the illness, although further research is needed. The randomized, double-blind MELIA trial of metformin plus lifestyle intervention in antipsychotic-induced weight gain is ongoing. Starting metformin as a preventive measure at the same time as antipsychotic therapy may help to limit excess weight gain. 

Research continues on the potential benefit of adding weight loss medications, including glucagon-like peptide-1 (GLP-1) receptor agonists, to antipsychotics. Daily liraglutide is most widely studied, but a published case series with weekly semaglutide also demonstrated weight loss in this setting. Liraglutide also has shown beneficial cardiometabolic effects in patients using antipsychotic medications. More studies of these drugs and of GLP-1/glucose-dependent insulinotropic polypeptide agonists are needed to elucidate the optimal use of these therapies for patients with schizophrenia.

There are few other effective ways to mitigate weight gain with olanzapine. Patients should be counseled on nutrition and lifestyle modifications. Evidence supports improvement with structured lifestyle modifications across a range of patients with less severe mental health issues, and structured programs combined with motivational interviewing were associated with reductions in antipsychotic-induced weight gain in patients with severe mental illness. As with any patient with obesity, however, the success of lifestyle modifications is heavily dependent on the individual's ability and motivation to comply with recommended interventions. 

Nonpharmacologic interventions to address joint pain include heat or cold compresses, physical therapy, and strength and resistance training to improve the strength of muscles supporting the joints. If these measures are ineffective, nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen, naproxen, meloxicam, diclofenac, or celecoxib may be used with regular follow-up to assess cardiovascular and gastrointestinal health. Topical NSAIDs also may be useful. For more intractable joint pain, options include injecting a corticosteroid or sodium hyaluronate into the affected joints or joint replacement. 

Carolyn Newberry, MD, Assistant Professor of Medicine, Director of GI Nutrition, Innovative Center for Health and Nutrition in Gastroenterology (ICHANGE), Division of Gastroenterology, Weill Cornell Medical Center, New York, NY.

Disclosure: Carolyn Newberry, MD, has disclosed the following relevant financial relationships:

Serve(d) as a speaker or a member of a speakers bureau for: Baster International; InBody.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

Overall, persons with schizophrenia are more likely than the general population to be overweight and have cardiovascular risk factors before starting treatment with antipsychotics, and such treatment generally worsens these measures. Weight gain and associated morbidity and mortality are common side effects of antipsychotic medications. Olanzapine is associated with significant weight gain of 7% or more, higher than other second-generation antipsychotics. Olanzapine treatment is the major contributor to this patient's additional weight gain over the past 2 years. This added weight has translated to excess wear and tear on her joints, leading to evidence of osteoarthritis. Treatment with olanzapine is also independently associated with detrimental changes in cardiometabolic parameters.

Interventions to prevent or mitigate weight gain with antipsychotics are limited. In general, the American Psychiatric Association does not recommend switching antipsychotics for patients whose schizophrenia is well managed. However, there is increasing evidence that metformin may have a role in mitigating weight gain as well as beneficially modifying cardiometabolic factors in patients with schizophrenia being treated with olanzapine. A systematic review of emerging evidence with metformin in patients with schizophrenia suggests that metformin may also improve some cognitive symptoms of the illness, although further research is needed. The randomized, double-blind MELIA trial of metformin plus lifestyle intervention in antipsychotic-induced weight gain is ongoing. Starting metformin as a preventive measure at the same time as antipsychotic therapy may help to limit excess weight gain. 

Research continues on the potential benefit of adding weight loss medications, including glucagon-like peptide-1 (GLP-1) receptor agonists, to antipsychotics. Daily liraglutide is most widely studied, but a published case series with weekly semaglutide also demonstrated weight loss in this setting. Liraglutide also has shown beneficial cardiometabolic effects in patients using antipsychotic medications. More studies of these drugs and of GLP-1/glucose-dependent insulinotropic polypeptide agonists are needed to elucidate the optimal use of these therapies for patients with schizophrenia.

There are few other effective ways to mitigate weight gain with olanzapine. Patients should be counseled on nutrition and lifestyle modifications. Evidence supports improvement with structured lifestyle modifications across a range of patients with less severe mental health issues, and structured programs combined with motivational interviewing were associated with reductions in antipsychotic-induced weight gain in patients with severe mental illness. As with any patient with obesity, however, the success of lifestyle modifications is heavily dependent on the individual's ability and motivation to comply with recommended interventions. 

Nonpharmacologic interventions to address joint pain include heat or cold compresses, physical therapy, and strength and resistance training to improve the strength of muscles supporting the joints. If these measures are ineffective, nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen, naproxen, meloxicam, diclofenac, or celecoxib may be used with regular follow-up to assess cardiovascular and gastrointestinal health. Topical NSAIDs also may be useful. For more intractable joint pain, options include injecting a corticosteroid or sodium hyaluronate into the affected joints or joint replacement. 

Carolyn Newberry, MD, Assistant Professor of Medicine, Director of GI Nutrition, Innovative Center for Health and Nutrition in Gastroenterology (ICHANGE), Division of Gastroenterology, Weill Cornell Medical Center, New York, NY.

Disclosure: Carolyn Newberry, MD, has disclosed the following relevant financial relationships:

Serve(d) as a speaker or a member of a speakers bureau for: Baster International; InBody.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

Overall, persons with schizophrenia are more likely than the general population to be overweight and have cardiovascular risk factors before starting treatment with antipsychotics, and such treatment generally worsens these measures. Weight gain and associated morbidity and mortality are common side effects of antipsychotic medications. Olanzapine is associated with significant weight gain of 7% or more, higher than other second-generation antipsychotics. Olanzapine treatment is the major contributor to this patient's additional weight gain over the past 2 years. This added weight has translated to excess wear and tear on her joints, leading to evidence of osteoarthritis. Treatment with olanzapine is also independently associated with detrimental changes in cardiometabolic parameters.

Interventions to prevent or mitigate weight gain with antipsychotics are limited. In general, the American Psychiatric Association does not recommend switching antipsychotics for patients whose schizophrenia is well managed. However, there is increasing evidence that metformin may have a role in mitigating weight gain as well as beneficially modifying cardiometabolic factors in patients with schizophrenia being treated with olanzapine. A systematic review of emerging evidence with metformin in patients with schizophrenia suggests that metformin may also improve some cognitive symptoms of the illness, although further research is needed. The randomized, double-blind MELIA trial of metformin plus lifestyle intervention in antipsychotic-induced weight gain is ongoing. Starting metformin as a preventive measure at the same time as antipsychotic therapy may help to limit excess weight gain. 

Research continues on the potential benefit of adding weight loss medications, including glucagon-like peptide-1 (GLP-1) receptor agonists, to antipsychotics. Daily liraglutide is most widely studied, but a published case series with weekly semaglutide also demonstrated weight loss in this setting. Liraglutide also has shown beneficial cardiometabolic effects in patients using antipsychotic medications. More studies of these drugs and of GLP-1/glucose-dependent insulinotropic polypeptide agonists are needed to elucidate the optimal use of these therapies for patients with schizophrenia.

There are few other effective ways to mitigate weight gain with olanzapine. Patients should be counseled on nutrition and lifestyle modifications. Evidence supports improvement with structured lifestyle modifications across a range of patients with less severe mental health issues, and structured programs combined with motivational interviewing were associated with reductions in antipsychotic-induced weight gain in patients with severe mental illness. As with any patient with obesity, however, the success of lifestyle modifications is heavily dependent on the individual's ability and motivation to comply with recommended interventions. 

Nonpharmacologic interventions to address joint pain include heat or cold compresses, physical therapy, and strength and resistance training to improve the strength of muscles supporting the joints. If these measures are ineffective, nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen, naproxen, meloxicam, diclofenac, or celecoxib may be used with regular follow-up to assess cardiovascular and gastrointestinal health. Topical NSAIDs also may be useful. For more intractable joint pain, options include injecting a corticosteroid or sodium hyaluronate into the affected joints or joint replacement. 

Carolyn Newberry, MD, Assistant Professor of Medicine, Director of GI Nutrition, Innovative Center for Health and Nutrition in Gastroenterology (ICHANGE), Division of Gastroenterology, Weill Cornell Medical Center, New York, NY.

Disclosure: Carolyn Newberry, MD, has disclosed the following relevant financial relationships:

Serve(d) as a speaker or a member of a speakers bureau for: Baster International; InBody.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

Medications classified as anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb), a relatively new category of migraine therapy, have shown strong evidence of efficacy for migraine treatment and prevention. However, as these medications — which include Aimovig (erenumab), Emgality (galcanezumab), Ajovy (fremanezumab), and Vyepti (eptinezumab) — are new, their long-term outcomes are not known; in addition, they are expensive and they do not work for everyone. Patients who are doing relatively well on other medications might ask about switching to one of the anti-CGRP mAb so that they can experience the better outcomes and low side-effect profile that they've been hearing about. New research is showing some prognostic indicators that can help identify which patients might experience a better response to anti-CGRP mAb.

A prospective real-world study published in the May 2024 issue of Journal of Neurology, Neurosurgery, and Psychiatry included 5818 patients who had been treated with an anti-CGRP mAb for high-frequency episodic or chronic migraine. The researchers assessed responses after 6 months of use, defining a good response as ≥50% reduction in monthly headache days and excellent response as ≥75% reduction in monthly headache days. They found that several pretreatment baseline factors were predictors of a good or excellent 6-month response: older age, the presence of unilateral pain, the absence of depression, fewer monthly migraine days, and lower Migraine Disability Assessment (MIDAS) score. Notably, men and women experienced comparable outcomes. While it's not completely clear why these factors were associated with better responses to anti-CGRP mAb, the results could help in selecting patients who might or might not benefit from this new medication class.

Results of a prospective study published in the May 2024 in The Journal of Headache and Pain demonstrated that patients treated with eptinezumab for 3 months experienced a reduction of monthly headaches, migraines, and the use of acute medication. The patients who had previously had an inadequate response to or were unable to tolerate other anti-CGRP mAb (erenumab, galcanezumab, fremanezumab) were less likely to experience improvement with eptinezumab than patients who had not had previous unsuccessful attempts with anti-CGRP mAb. This suggests that it might not be beneficial for patents to try multiple medications in this category if they have had an inadequate response or intolerability to others in the same drug class.

Lifestyle factors can play a role in migraine outcomes and may reduce the need for medication. A study published in The Journal of Headache and Pain in May 2024 examined the relationship between migraine and the American Heart Association (AHA) Guidelines for Cardiovascular Health recommended lifestyle factors. The study included 332,895 participants, with a median follow-up of 13.58 years. Researchers found that maintaining targeted or recommended body mass index (BMI), physical activity, sleep duration, sleep pattern, and sedentary time were associated with substantial reductions in migraine risk.

Diet, another lifestyle factor, can also have an effect on migraine. Avoiding dietary triggers is a well-known adjustment that many patients are advised to make. Overall diet quality can play a role in migraine outcomes as well. According to a study published in the May 2024 issue of Nutritional Neuroscience, participants who followed a diet that qualified as having a high Carbohydrate Quality Index (CQI) had lower migraine severity and duration than participants whose diets did not qualify as high CQI. The study included 266 women (age 18-45 years), using a 147-item food frequency questionnaire to assess CQI. The CQI, a relatively new index for measuring carbohydrate quality, includes four components: glycemic index, dietary fiber intake, ratio of whole grain to total grain, ratio of solid carbohydrates to total (solid + liquid) carbohydrates.¹ A low glycemic index and higher scores for the other three factors translates to a high CQI.

While the results of the AHA/migraine study and the CQI/migraine study are interesting, the physiologic reasons for the outcomes and validation of the results need further investigation. It's not clear whether the decrease in migraines that's associated with optimal carbohydrate intake is associated with outcomes such as low BMI or better sleep, or whether carbohydrate metabolism could be an independent factor.

Predictive factors can be beneficial in making migraine treatment decisions. While trial and error will always remain part of optimal migraine therapy, customizing treatment on the basis of an individual patient's characteristics can help in reaching an effective treatment and better quality of life sooner.

Additional References

1. Sawicki CM, Lichtenstein AH, Rogers GT, et al. Comparison of indices of carbohydrate quality and food sources of dietary fiber on longitudinal changes in waist circumference in the Framingham Offspring Cohort. Nutrients. 2021;13:997. Source

Medications classified as anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb), a relatively new category of migraine therapy, have shown strong evidence of efficacy for migraine treatment and prevention. However, as these medications — which include Aimovig (erenumab), Emgality (galcanezumab), Ajovy (fremanezumab), and Vyepti (eptinezumab) — are new, their long-term outcomes are not known; in addition, they are expensive and they do not work for everyone. Patients who are doing relatively well on other medications might ask about switching to one of the anti-CGRP mAb so that they can experience the better outcomes and low side-effect profile that they've been hearing about. New research is showing some prognostic indicators that can help identify which patients might experience a better response to anti-CGRP mAb.

A prospective real-world study published in the May 2024 issue of Journal of Neurology, Neurosurgery, and Psychiatry included 5818 patients who had been treated with an anti-CGRP mAb for high-frequency episodic or chronic migraine. The researchers assessed responses after 6 months of use, defining a good response as ≥50% reduction in monthly headache days and excellent response as ≥75% reduction in monthly headache days. They found that several pretreatment baseline factors were predictors of a good or excellent 6-month response: older age, the presence of unilateral pain, the absence of depression, fewer monthly migraine days, and lower Migraine Disability Assessment (MIDAS) score. Notably, men and women experienced comparable outcomes. While it's not completely clear why these factors were associated with better responses to anti-CGRP mAb, the results could help in selecting patients who might or might not benefit from this new medication class.

Results of a prospective study published in the May 2024 in The Journal of Headache and Pain demonstrated that patients treated with eptinezumab for 3 months experienced a reduction of monthly headaches, migraines, and the use of acute medication. The patients who had previously had an inadequate response to or were unable to tolerate other anti-CGRP mAb (erenumab, galcanezumab, fremanezumab) were less likely to experience improvement with eptinezumab than patients who had not had previous unsuccessful attempts with anti-CGRP mAb. This suggests that it might not be beneficial for patents to try multiple medications in this category if they have had an inadequate response or intolerability to others in the same drug class.

Lifestyle factors can play a role in migraine outcomes and may reduce the need for medication. A study published in The Journal of Headache and Pain in May 2024 examined the relationship between migraine and the American Heart Association (AHA) Guidelines for Cardiovascular Health recommended lifestyle factors. The study included 332,895 participants, with a median follow-up of 13.58 years. Researchers found that maintaining targeted or recommended body mass index (BMI), physical activity, sleep duration, sleep pattern, and sedentary time were associated with substantial reductions in migraine risk.

Diet, another lifestyle factor, can also have an effect on migraine. Avoiding dietary triggers is a well-known adjustment that many patients are advised to make. Overall diet quality can play a role in migraine outcomes as well. According to a study published in the May 2024 issue of Nutritional Neuroscience, participants who followed a diet that qualified as having a high Carbohydrate Quality Index (CQI) had lower migraine severity and duration than participants whose diets did not qualify as high CQI. The study included 266 women (age 18-45 years), using a 147-item food frequency questionnaire to assess CQI. The CQI, a relatively new index for measuring carbohydrate quality, includes four components: glycemic index, dietary fiber intake, ratio of whole grain to total grain, ratio of solid carbohydrates to total (solid + liquid) carbohydrates.¹ A low glycemic index and higher scores for the other three factors translates to a high CQI.

While the results of the AHA/migraine study and the CQI/migraine study are interesting, the physiologic reasons for the outcomes and validation of the results need further investigation. It's not clear whether the decrease in migraines that's associated with optimal carbohydrate intake is associated with outcomes such as low BMI or better sleep, or whether carbohydrate metabolism could be an independent factor.

Predictive factors can be beneficial in making migraine treatment decisions. While trial and error will always remain part of optimal migraine therapy, customizing treatment on the basis of an individual patient's characteristics can help in reaching an effective treatment and better quality of life sooner.

Additional References

1. Sawicki CM, Lichtenstein AH, Rogers GT, et al. Comparison of indices of carbohydrate quality and food sources of dietary fiber on longitudinal changes in waist circumference in the Framingham Offspring Cohort. Nutrients. 2021;13:997. Source

Medications classified as anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb), a relatively new category of migraine therapy, have shown strong evidence of efficacy for migraine treatment and prevention. However, as these medications — which include Aimovig (erenumab), Emgality (galcanezumab), Ajovy (fremanezumab), and Vyepti (eptinezumab) — are new, their long-term outcomes are not known; in addition, they are expensive and they do not work for everyone. Patients who are doing relatively well on other medications might ask about switching to one of the anti-CGRP mAb so that they can experience the better outcomes and low side-effect profile that they've been hearing about. New research is showing some prognostic indicators that can help identify which patients might experience a better response to anti-CGRP mAb.

A prospective real-world study published in the May 2024 issue of Journal of Neurology, Neurosurgery, and Psychiatry included 5818 patients who had been treated with an anti-CGRP mAb for high-frequency episodic or chronic migraine. The researchers assessed responses after 6 months of use, defining a good response as ≥50% reduction in monthly headache days and excellent response as ≥75% reduction in monthly headache days. They found that several pretreatment baseline factors were predictors of a good or excellent 6-month response: older age, the presence of unilateral pain, the absence of depression, fewer monthly migraine days, and lower Migraine Disability Assessment (MIDAS) score. Notably, men and women experienced comparable outcomes. While it's not completely clear why these factors were associated with better responses to anti-CGRP mAb, the results could help in selecting patients who might or might not benefit from this new medication class.

Results of a prospective study published in the May 2024 in The Journal of Headache and Pain demonstrated that patients treated with eptinezumab for 3 months experienced a reduction of monthly headaches, migraines, and the use of acute medication. The patients who had previously had an inadequate response to or were unable to tolerate other anti-CGRP mAb (erenumab, galcanezumab, fremanezumab) were less likely to experience improvement with eptinezumab than patients who had not had previous unsuccessful attempts with anti-CGRP mAb. This suggests that it might not be beneficial for patents to try multiple medications in this category if they have had an inadequate response or intolerability to others in the same drug class.

Lifestyle factors can play a role in migraine outcomes and may reduce the need for medication. A study published in The Journal of Headache and Pain in May 2024 examined the relationship between migraine and the American Heart Association (AHA) Guidelines for Cardiovascular Health recommended lifestyle factors. The study included 332,895 participants, with a median follow-up of 13.58 years. Researchers found that maintaining targeted or recommended body mass index (BMI), physical activity, sleep duration, sleep pattern, and sedentary time were associated with substantial reductions in migraine risk.

Diet, another lifestyle factor, can also have an effect on migraine. Avoiding dietary triggers is a well-known adjustment that many patients are advised to make. Overall diet quality can play a role in migraine outcomes as well. According to a study published in the May 2024 issue of Nutritional Neuroscience, participants who followed a diet that qualified as having a high Carbohydrate Quality Index (CQI) had lower migraine severity and duration than participants whose diets did not qualify as high CQI. The study included 266 women (age 18-45 years), using a 147-item food frequency questionnaire to assess CQI. The CQI, a relatively new index for measuring carbohydrate quality, includes four components: glycemic index, dietary fiber intake, ratio of whole grain to total grain, ratio of solid carbohydrates to total (solid + liquid) carbohydrates.¹ A low glycemic index and higher scores for the other three factors translates to a high CQI.

While the results of the AHA/migraine study and the CQI/migraine study are interesting, the physiologic reasons for the outcomes and validation of the results need further investigation. It's not clear whether the decrease in migraines that's associated with optimal carbohydrate intake is associated with outcomes such as low BMI or better sleep, or whether carbohydrate metabolism could be an independent factor.

Predictive factors can be beneficial in making migraine treatment decisions. While trial and error will always remain part of optimal migraine therapy, customizing treatment on the basis of an individual patient's characteristics can help in reaching an effective treatment and better quality of life sooner.

Additional References

1. Sawicki CM, Lichtenstein AH, Rogers GT, et al. Comparison of indices of carbohydrate quality and food sources of dietary fiber on longitudinal changes in waist circumference in the Framingham Offspring Cohort. Nutrients. 2021;13:997. Source