Opinion

In January 2024, the American Academy of Dermatology released updated clinical guidelines for the treatment of acne. These guidelines include 18 evidence-based recommendations.

As primary care physicians, we commonly encounter acne vulgaris in our practices. While it may not be a life-threatening condition, it deeply affects the quality of life for many who suffer from it. It can be accompanied by stigmatization and bullying and can affect a person’s self-esteem; it can lead to suicidal ideation. It is important to treat it and know when to refer to a dermatologist.

According to the AAD, acne is the most common skin condition, affecting 50 million Americans annually. It can occur at any stage in life, often starting during puberty. It is so common that at least 85% of people between the ages of 12 and 24 experience at least mild acne.

The guidelines stress using multimodal therapies combining multiple mechanisms of action. For example, they show strong evidence for using topical retinoids with topical benzoyl peroxide or topical retinoids with topical antibiotics. They recommend against using oral antibiotics, except in severe cases, to prevent antibiotic resistance. The strongest evidence regarding antibiotics shows doxycycline or minocycline to be the most effective for treating acne and these can be combined with topical medications.

These guidelines also include isotretinoin to be used for severe acne patients, who are defined as “patients with psychosocial burden or scarring.” They recommend monitoring liver function and lipids as good practice and mandatory pregnancy prevention. These guidelines find no conclusive evidence for physical modalities such as lesion extraction, chemical peels, use of laser and light-based devices, microneedling, use of radiofrequency devices, and photodynamic therapy.

A conditional recommendation is given for the use of combined oral contraception pills and spironolactone. The AAD advises considering the risks of these agents along with other conditions present that they may be useful for.

In primary care, we see many complicated patients and often acne is not considered a serious condition. However, it can be as life-altering to the patient as other chronic diseases such as rheumatoid arthritis. We need to know the appropriate management of acne and start following the evidence-based guidelines. Acne needs follow-up as close as for other chronic diseases. We need to be able to assess the severity of disease and the effectiveness of treatments we have prescribed.

Some patients may be embarrassed to start the discussion about acne. If the patient doesn’t initiate the discussion, we should in an empathetic way. Acne is one of those diseases that doesn’t need any diagnostic tests to discover as it is readily apparent right in front of us.

Some patients may not be bothered by it, but for others, it may be ruining their lives, and they just don’t feel comfortable starting the conversation. Offering them a treatment will alleviate their disease but may also change their lives for the better.

Acne is also one of those conditions that has a host of misinformation and myths surrounding it. These myths range from dietary recommendations to hygiene and many others. As physicians, we need to educate ourselves about these myths and misconceptions. Patients will have questions regarding them and we need to be able to give them answers to their questions. We also shouldn’t give out misinformation ourselves. The evidence around acne treatment is readily available.

Given the availability of multiple acne therapies, shared-decision making is important. We need to discuss options with the patients and devise the best treatment regimen for them. If our therapies are not getting the results we would like, we need to consider referring the patient to a dermatologist.

We need to remember that acne is not just a cosmetic disease. It affects the lives of those suffering from it and we need to address it like any other chronic disease.
 

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J.

In January 2024, the American Academy of Dermatology released updated clinical guidelines for the treatment of acne. These guidelines include 18 evidence-based recommendations.

As primary care physicians, we commonly encounter acne vulgaris in our practices. While it may not be a life-threatening condition, it deeply affects the quality of life for many who suffer from it. It can be accompanied by stigmatization and bullying and can affect a person’s self-esteem; it can lead to suicidal ideation. It is important to treat it and know when to refer to a dermatologist.

According to the AAD, acne is the most common skin condition, affecting 50 million Americans annually. It can occur at any stage in life, often starting during puberty. It is so common that at least 85% of people between the ages of 12 and 24 experience at least mild acne.

The guidelines stress using multimodal therapies combining multiple mechanisms of action. For example, they show strong evidence for using topical retinoids with topical benzoyl peroxide or topical retinoids with topical antibiotics. They recommend against using oral antibiotics, except in severe cases, to prevent antibiotic resistance. The strongest evidence regarding antibiotics shows doxycycline or minocycline to be the most effective for treating acne and these can be combined with topical medications.

These guidelines also include isotretinoin to be used for severe acne patients, who are defined as “patients with psychosocial burden or scarring.” They recommend monitoring liver function and lipids as good practice and mandatory pregnancy prevention. These guidelines find no conclusive evidence for physical modalities such as lesion extraction, chemical peels, use of laser and light-based devices, microneedling, use of radiofrequency devices, and photodynamic therapy.

A conditional recommendation is given for the use of combined oral contraception pills and spironolactone. The AAD advises considering the risks of these agents along with other conditions present that they may be useful for.

In primary care, we see many complicated patients and often acne is not considered a serious condition. However, it can be as life-altering to the patient as other chronic diseases such as rheumatoid arthritis. We need to know the appropriate management of acne and start following the evidence-based guidelines. Acne needs follow-up as close as for other chronic diseases. We need to be able to assess the severity of disease and the effectiveness of treatments we have prescribed.

Some patients may be embarrassed to start the discussion about acne. If the patient doesn’t initiate the discussion, we should in an empathetic way. Acne is one of those diseases that doesn’t need any diagnostic tests to discover as it is readily apparent right in front of us.

Some patients may not be bothered by it, but for others, it may be ruining their lives, and they just don’t feel comfortable starting the conversation. Offering them a treatment will alleviate their disease but may also change their lives for the better.

Acne is also one of those conditions that has a host of misinformation and myths surrounding it. These myths range from dietary recommendations to hygiene and many others. As physicians, we need to educate ourselves about these myths and misconceptions. Patients will have questions regarding them and we need to be able to give them answers to their questions. We also shouldn’t give out misinformation ourselves. The evidence around acne treatment is readily available.

Given the availability of multiple acne therapies, shared-decision making is important. We need to discuss options with the patients and devise the best treatment regimen for them. If our therapies are not getting the results we would like, we need to consider referring the patient to a dermatologist.

We need to remember that acne is not just a cosmetic disease. It affects the lives of those suffering from it and we need to address it like any other chronic disease.
 

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J.

In January 2024, the American Academy of Dermatology released updated clinical guidelines for the treatment of acne. These guidelines include 18 evidence-based recommendations.

As primary care physicians, we commonly encounter acne vulgaris in our practices. While it may not be a life-threatening condition, it deeply affects the quality of life for many who suffer from it. It can be accompanied by stigmatization and bullying and can affect a person’s self-esteem; it can lead to suicidal ideation. It is important to treat it and know when to refer to a dermatologist.

According to the AAD, acne is the most common skin condition, affecting 50 million Americans annually. It can occur at any stage in life, often starting during puberty. It is so common that at least 85% of people between the ages of 12 and 24 experience at least mild acne.

The guidelines stress using multimodal therapies combining multiple mechanisms of action. For example, they show strong evidence for using topical retinoids with topical benzoyl peroxide or topical retinoids with topical antibiotics. They recommend against using oral antibiotics, except in severe cases, to prevent antibiotic resistance. The strongest evidence regarding antibiotics shows doxycycline or minocycline to be the most effective for treating acne and these can be combined with topical medications.

These guidelines also include isotretinoin to be used for severe acne patients, who are defined as “patients with psychosocial burden or scarring.” They recommend monitoring liver function and lipids as good practice and mandatory pregnancy prevention. These guidelines find no conclusive evidence for physical modalities such as lesion extraction, chemical peels, use of laser and light-based devices, microneedling, use of radiofrequency devices, and photodynamic therapy.

A conditional recommendation is given for the use of combined oral contraception pills and spironolactone. The AAD advises considering the risks of these agents along with other conditions present that they may be useful for.

In primary care, we see many complicated patients and often acne is not considered a serious condition. However, it can be as life-altering to the patient as other chronic diseases such as rheumatoid arthritis. We need to know the appropriate management of acne and start following the evidence-based guidelines. Acne needs follow-up as close as for other chronic diseases. We need to be able to assess the severity of disease and the effectiveness of treatments we have prescribed.

Some patients may be embarrassed to start the discussion about acne. If the patient doesn’t initiate the discussion, we should in an empathetic way. Acne is one of those diseases that doesn’t need any diagnostic tests to discover as it is readily apparent right in front of us.

Some patients may not be bothered by it, but for others, it may be ruining their lives, and they just don’t feel comfortable starting the conversation. Offering them a treatment will alleviate their disease but may also change their lives for the better.

Acne is also one of those conditions that has a host of misinformation and myths surrounding it. These myths range from dietary recommendations to hygiene and many others. As physicians, we need to educate ourselves about these myths and misconceptions. Patients will have questions regarding them and we need to be able to give them answers to their questions. We also shouldn’t give out misinformation ourselves. The evidence around acne treatment is readily available.

Given the availability of multiple acne therapies, shared-decision making is important. We need to discuss options with the patients and devise the best treatment regimen for them. If our therapies are not getting the results we would like, we need to consider referring the patient to a dermatologist.

We need to remember that acne is not just a cosmetic disease. It affects the lives of those suffering from it and we need to address it like any other chronic disease.
 

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J.

This article was originally published on February 10 in Eric Topol’s substack “Ground Truths.”

It’s astounding how devious cancer cells and tumor tissue can be. This week in Science we learned how certain lung cancer cells can function like “Catch Me If You Can” — changing their driver mutation and cell identity to escape targeted therapy. This histologic transformation, as seen in an experimental model, is just one of so many cancer tricks that we are learning about.

Recently, as shown by single-cell sequencing, cancer cells can steal the mitochondria from T cells, a double whammy that turbocharges cancer cells with the hijacked fuel supply and, at the same time, dismantles the immune response.

Last week, we saw how tumor cells can release a virus-like protein that unleashes a vicious autoimmune response.

And then there’s the finding that cancer cell spread predominantly is occurring while we sleep.

As I previously reviewed, the ability for cancer cells to hijack neurons and neural circuits is now well established, no less their ability to reprogram neurons to become adrenergic and stimulate tumor progression, and interfere with the immune response. Stay tuned on that for a new Ground Truths podcast with Prof Michelle Monje, a leader in cancer neuroscience, which will post soon.

Add advancing age’s immunosenescence as yet another challenge to the long and growing list of formidable ways that cancer cells, and the tumor microenvironment, evade our immune response.

An Ever-Expanding Armamentarium

All of this is telling us how we need to ramp up our game if we are going to be able to use our immune system to quash a cancer. Fortunately, we have abundant and ever-growing capabilities for doing just that.

Immune Checkpoint Inhibitors

The field of immunotherapies took off with the immune checkpoint inhibitors, first approved by the FDA in 2011, that take the brakes off of T cells, with the programmed death-1 (PD-1), PD-ligand1, and anti-CTLA-4 monoclonal antibodies.

But we’re clearly learning they are not enough to prevail over cancer with common recurrences, only short term success in most patients, with some notable exceptions. Adding other immune response strategies, such as a vaccine, or antibody-drug conjugates, or engineered T cells, are showing improved chances for success.

Therapeutic Cancer Vaccines

There are many therapeutic cancer vaccines in the works, as reviewed in depth here.

Here’s a list of ongoing clinical trials of cancer vaccines. You’ll note most of these are on top of a checkpoint inhibitor and use personalized neoantigens (cancer cell surface proteins) derived from sequencing (whole-exome or whole genome, RNA-sequencing and HLA-profiling) the patient’s tumor.

An example of positive findings is with the combination of an mRNA-nanoparticle vaccine with up to 34 personalized neoantigens and pembrolizumab (Keytruda) vs pembrolizumab alone in advanced melanoma after resection, with improved outcomes at 3-year follow-up, cutting death or relapse rate in half.

Antibody-Drug Conjugates (ADC)

There is considerable excitement about antibody-drug conjugates (ADC) whereby a linker is used to attach a chemotherapy agent to the checkpoint inhibitor antibody, specifically targeting the cancer cell and facilitating entry of the chemotherapy into the cell. Akin to these are bispecific antibodies (BiTEs, binding to a tumor antigen and T cell receptor simultaneously), both of these conjugates acting as “biologic” or “guided” missiles.

A very good example of the potency of an ADC was seen in a “HER2-low” breast cancer randomized trial. The absence or very low expression or amplification of the HER2 receptor is common in breast cancer and successful treatment has been elusive. A randomized trial of an ADC (trastuzumab deruxtecan) compared to physician’s choice therapy demonstrated a marked success for progression-free survival in HER2-low patients, which was characterized as “unheard-of success” by media coverage.

This strategy is being used to target some of the most difficult cancer driver mutations such as TP53 and KRAS.

Oncolytic Viruses

Modifying viruses to infect the tumor and make it more visible to the immune system, potentiating anti-tumor responses, known as oncolytic viruses, have been proposed as a way to rev up the immune response for a long time but without positive Phase 3 clinical trials.

After decades of failure, a recent trial in refractory bladder cancer showed marked success, along with others, summarized here, now providing very encouraging results. It looks like oncolytic viruses are on a comeback path.

Engineering T Cells (Chimeric Antigen Receptor [CAR-T])

As I recently reviewed, there are over 500 ongoing clinical trials to build on the success of the first CAR-T approval for leukemia 7 years ago. I won’t go through that all again here, but to reiterate most of the success to date has been in “liquid” blood (leukemia and lymphoma) cancer tumors. This week in Nature is the discovery of a T cell cancer mutation, a gene fusion CARD11-PIK3R3, from a T cell lymphoma that can potentially be used to augment CAR-T efficacy. It has pronounced and prolonged effects in the experimental model. Instead of 1 million cells needed for treatment, even 20,000 were enough to melt the tumor. This is a noteworthy discovery since CAR-T work to date has largely not exploited such naturally occurring mutations, while instead concentrating on those seen in the patient’s set of key tumor mutations.

As currently conceived, CAR-T, and what is being referred to more broadly as adoptive cell therapies, involves removing T cells from the patient’s body and engineering their activation, then reintroducing them back to the patient. This is laborious, technically difficult, and very expensive. Recently, the idea of achieving all of this via an injection of virus that specifically infects T cells and inserts the genes needed, was advanced by two biotech companies with preclinical results, one in non-human primates.

Gearing up to meet the challenge of solid tumor CAR-T intervention, there’s more work using CRISPR genome editing of T cell receptors. A.I. is increasingly being exploited to process the data from sequencing and identify optimal neoantigens.

Instead of just CAR-T, we’re seeing the emergence of CAR-macrophage and CAR-natural killer (NK) cells strategies, and rapidly expanding potential combinations of all the strategies I’ve mentioned. No less, there’s been maturation of on-off suicide switches programmed in, to limit cytokine release and promote safety of these interventions. Overall, major side effects of immunotherapies are not only cytokine release syndromes, but also include interstitial pneumonitis and neurotoxicity.

Summary

Given the multitude of ways cancer cells and tumor tissue can evade our immune response, durably successful treatment remains a daunting challenge. But the ingenuity of so many different approaches to unleash our immune response, and their combinations, provides considerable hope that we’ll increasingly meet the challenge in the years ahead. We have clearly learned that combining different immunotherapy strategies will be essential for many patients with the most resilient solid tumors.

Of concern, as noted by a recent editorial in The Lancet, entitled “Cancer Research Equity: Innovations For The Many, Not The Few,” is that these individualized, sophisticated strategies are not scalable; they will have limited reach and benefit. The movement towards “off the shelf” CAR-T and inexpensive, orally active checkpoint inhibitors may help mitigate this issue.

Notwithstanding this important concern, we’re seeing an array of diverse and potent immunotherapy strategies that are providing highly encouraging results, engendering more excitement than we’ve seen in this space for some time. These should propel substantial improvements in outcomes for patients in the years ahead. It can’t happen soon enough.

Thanks for reading this edition of Ground Truths. If you found it informative, please share it with your colleagues.

Dr. Topol has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for Dexcom; Illumina; Molecular Stethoscope; Quest Diagnostics; Blue Cross Blue Shield Association. Received research grant from National Institutes of Health.

A version of this article appeared on Medscape.com.

This article was originally published on February 10 in Eric Topol’s substack “Ground Truths.”

It’s astounding how devious cancer cells and tumor tissue can be. This week in Science we learned how certain lung cancer cells can function like “Catch Me If You Can” — changing their driver mutation and cell identity to escape targeted therapy. This histologic transformation, as seen in an experimental model, is just one of so many cancer tricks that we are learning about.

Recently, as shown by single-cell sequencing, cancer cells can steal the mitochondria from T cells, a double whammy that turbocharges cancer cells with the hijacked fuel supply and, at the same time, dismantles the immune response.

Last week, we saw how tumor cells can release a virus-like protein that unleashes a vicious autoimmune response.

And then there’s the finding that cancer cell spread predominantly is occurring while we sleep.

As I previously reviewed, the ability for cancer cells to hijack neurons and neural circuits is now well established, no less their ability to reprogram neurons to become adrenergic and stimulate tumor progression, and interfere with the immune response. Stay tuned on that for a new Ground Truths podcast with Prof Michelle Monje, a leader in cancer neuroscience, which will post soon.

Add advancing age’s immunosenescence as yet another challenge to the long and growing list of formidable ways that cancer cells, and the tumor microenvironment, evade our immune response.

An Ever-Expanding Armamentarium

All of this is telling us how we need to ramp up our game if we are going to be able to use our immune system to quash a cancer. Fortunately, we have abundant and ever-growing capabilities for doing just that.

Immune Checkpoint Inhibitors

The field of immunotherapies took off with the immune checkpoint inhibitors, first approved by the FDA in 2011, that take the brakes off of T cells, with the programmed death-1 (PD-1), PD-ligand1, and anti-CTLA-4 monoclonal antibodies.

But we’re clearly learning they are not enough to prevail over cancer with common recurrences, only short term success in most patients, with some notable exceptions. Adding other immune response strategies, such as a vaccine, or antibody-drug conjugates, or engineered T cells, are showing improved chances for success.

Therapeutic Cancer Vaccines

There are many therapeutic cancer vaccines in the works, as reviewed in depth here.

Here’s a list of ongoing clinical trials of cancer vaccines. You’ll note most of these are on top of a checkpoint inhibitor and use personalized neoantigens (cancer cell surface proteins) derived from sequencing (whole-exome or whole genome, RNA-sequencing and HLA-profiling) the patient’s tumor.

An example of positive findings is with the combination of an mRNA-nanoparticle vaccine with up to 34 personalized neoantigens and pembrolizumab (Keytruda) vs pembrolizumab alone in advanced melanoma after resection, with improved outcomes at 3-year follow-up, cutting death or relapse rate in half.

Antibody-Drug Conjugates (ADC)

There is considerable excitement about antibody-drug conjugates (ADC) whereby a linker is used to attach a chemotherapy agent to the checkpoint inhibitor antibody, specifically targeting the cancer cell and facilitating entry of the chemotherapy into the cell. Akin to these are bispecific antibodies (BiTEs, binding to a tumor antigen and T cell receptor simultaneously), both of these conjugates acting as “biologic” or “guided” missiles.

A very good example of the potency of an ADC was seen in a “HER2-low” breast cancer randomized trial. The absence or very low expression or amplification of the HER2 receptor is common in breast cancer and successful treatment has been elusive. A randomized trial of an ADC (trastuzumab deruxtecan) compared to physician’s choice therapy demonstrated a marked success for progression-free survival in HER2-low patients, which was characterized as “unheard-of success” by media coverage.

This strategy is being used to target some of the most difficult cancer driver mutations such as TP53 and KRAS.

Oncolytic Viruses

Modifying viruses to infect the tumor and make it more visible to the immune system, potentiating anti-tumor responses, known as oncolytic viruses, have been proposed as a way to rev up the immune response for a long time but without positive Phase 3 clinical trials.

After decades of failure, a recent trial in refractory bladder cancer showed marked success, along with others, summarized here, now providing very encouraging results. It looks like oncolytic viruses are on a comeback path.

Engineering T Cells (Chimeric Antigen Receptor [CAR-T])

As I recently reviewed, there are over 500 ongoing clinical trials to build on the success of the first CAR-T approval for leukemia 7 years ago. I won’t go through that all again here, but to reiterate most of the success to date has been in “liquid” blood (leukemia and lymphoma) cancer tumors. This week in Nature is the discovery of a T cell cancer mutation, a gene fusion CARD11-PIK3R3, from a T cell lymphoma that can potentially be used to augment CAR-T efficacy. It has pronounced and prolonged effects in the experimental model. Instead of 1 million cells needed for treatment, even 20,000 were enough to melt the tumor. This is a noteworthy discovery since CAR-T work to date has largely not exploited such naturally occurring mutations, while instead concentrating on those seen in the patient’s set of key tumor mutations.

As currently conceived, CAR-T, and what is being referred to more broadly as adoptive cell therapies, involves removing T cells from the patient’s body and engineering their activation, then reintroducing them back to the patient. This is laborious, technically difficult, and very expensive. Recently, the idea of achieving all of this via an injection of virus that specifically infects T cells and inserts the genes needed, was advanced by two biotech companies with preclinical results, one in non-human primates.

Gearing up to meet the challenge of solid tumor CAR-T intervention, there’s more work using CRISPR genome editing of T cell receptors. A.I. is increasingly being exploited to process the data from sequencing and identify optimal neoantigens.

Instead of just CAR-T, we’re seeing the emergence of CAR-macrophage and CAR-natural killer (NK) cells strategies, and rapidly expanding potential combinations of all the strategies I’ve mentioned. No less, there’s been maturation of on-off suicide switches programmed in, to limit cytokine release and promote safety of these interventions. Overall, major side effects of immunotherapies are not only cytokine release syndromes, but also include interstitial pneumonitis and neurotoxicity.

Summary

Given the multitude of ways cancer cells and tumor tissue can evade our immune response, durably successful treatment remains a daunting challenge. But the ingenuity of so many different approaches to unleash our immune response, and their combinations, provides considerable hope that we’ll increasingly meet the challenge in the years ahead. We have clearly learned that combining different immunotherapy strategies will be essential for many patients with the most resilient solid tumors.

Of concern, as noted by a recent editorial in The Lancet, entitled “Cancer Research Equity: Innovations For The Many, Not The Few,” is that these individualized, sophisticated strategies are not scalable; they will have limited reach and benefit. The movement towards “off the shelf” CAR-T and inexpensive, orally active checkpoint inhibitors may help mitigate this issue.

Notwithstanding this important concern, we’re seeing an array of diverse and potent immunotherapy strategies that are providing highly encouraging results, engendering more excitement than we’ve seen in this space for some time. These should propel substantial improvements in outcomes for patients in the years ahead. It can’t happen soon enough.

Thanks for reading this edition of Ground Truths. If you found it informative, please share it with your colleagues.

Dr. Topol has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for Dexcom; Illumina; Molecular Stethoscope; Quest Diagnostics; Blue Cross Blue Shield Association. Received research grant from National Institutes of Health.

A version of this article appeared on Medscape.com.

This article was originally published on February 10 in Eric Topol’s substack “Ground Truths.”

It’s astounding how devious cancer cells and tumor tissue can be. This week in Science we learned how certain lung cancer cells can function like “Catch Me If You Can” — changing their driver mutation and cell identity to escape targeted therapy. This histologic transformation, as seen in an experimental model, is just one of so many cancer tricks that we are learning about.

Recently, as shown by single-cell sequencing, cancer cells can steal the mitochondria from T cells, a double whammy that turbocharges cancer cells with the hijacked fuel supply and, at the same time, dismantles the immune response.

Last week, we saw how tumor cells can release a virus-like protein that unleashes a vicious autoimmune response.

And then there’s the finding that cancer cell spread predominantly is occurring while we sleep.

As I previously reviewed, the ability for cancer cells to hijack neurons and neural circuits is now well established, no less their ability to reprogram neurons to become adrenergic and stimulate tumor progression, and interfere with the immune response. Stay tuned on that for a new Ground Truths podcast with Prof Michelle Monje, a leader in cancer neuroscience, which will post soon.

Add advancing age’s immunosenescence as yet another challenge to the long and growing list of formidable ways that cancer cells, and the tumor microenvironment, evade our immune response.

An Ever-Expanding Armamentarium

All of this is telling us how we need to ramp up our game if we are going to be able to use our immune system to quash a cancer. Fortunately, we have abundant and ever-growing capabilities for doing just that.

Immune Checkpoint Inhibitors

The field of immunotherapies took off with the immune checkpoint inhibitors, first approved by the FDA in 2011, that take the brakes off of T cells, with the programmed death-1 (PD-1), PD-ligand1, and anti-CTLA-4 monoclonal antibodies.

But we’re clearly learning they are not enough to prevail over cancer with common recurrences, only short term success in most patients, with some notable exceptions. Adding other immune response strategies, such as a vaccine, or antibody-drug conjugates, or engineered T cells, are showing improved chances for success.

Therapeutic Cancer Vaccines

There are many therapeutic cancer vaccines in the works, as reviewed in depth here.

Here’s a list of ongoing clinical trials of cancer vaccines. You’ll note most of these are on top of a checkpoint inhibitor and use personalized neoantigens (cancer cell surface proteins) derived from sequencing (whole-exome or whole genome, RNA-sequencing and HLA-profiling) the patient’s tumor.

An example of positive findings is with the combination of an mRNA-nanoparticle vaccine with up to 34 personalized neoantigens and pembrolizumab (Keytruda) vs pembrolizumab alone in advanced melanoma after resection, with improved outcomes at 3-year follow-up, cutting death or relapse rate in half.

Antibody-Drug Conjugates (ADC)

There is considerable excitement about antibody-drug conjugates (ADC) whereby a linker is used to attach a chemotherapy agent to the checkpoint inhibitor antibody, specifically targeting the cancer cell and facilitating entry of the chemotherapy into the cell. Akin to these are bispecific antibodies (BiTEs, binding to a tumor antigen and T cell receptor simultaneously), both of these conjugates acting as “biologic” or “guided” missiles.

A very good example of the potency of an ADC was seen in a “HER2-low” breast cancer randomized trial. The absence or very low expression or amplification of the HER2 receptor is common in breast cancer and successful treatment has been elusive. A randomized trial of an ADC (trastuzumab deruxtecan) compared to physician’s choice therapy demonstrated a marked success for progression-free survival in HER2-low patients, which was characterized as “unheard-of success” by media coverage.

This strategy is being used to target some of the most difficult cancer driver mutations such as TP53 and KRAS.

Oncolytic Viruses

Modifying viruses to infect the tumor and make it more visible to the immune system, potentiating anti-tumor responses, known as oncolytic viruses, have been proposed as a way to rev up the immune response for a long time but without positive Phase 3 clinical trials.

After decades of failure, a recent trial in refractory bladder cancer showed marked success, along with others, summarized here, now providing very encouraging results. It looks like oncolytic viruses are on a comeback path.

Engineering T Cells (Chimeric Antigen Receptor [CAR-T])

As I recently reviewed, there are over 500 ongoing clinical trials to build on the success of the first CAR-T approval for leukemia 7 years ago. I won’t go through that all again here, but to reiterate most of the success to date has been in “liquid” blood (leukemia and lymphoma) cancer tumors. This week in Nature is the discovery of a T cell cancer mutation, a gene fusion CARD11-PIK3R3, from a T cell lymphoma that can potentially be used to augment CAR-T efficacy. It has pronounced and prolonged effects in the experimental model. Instead of 1 million cells needed for treatment, even 20,000 were enough to melt the tumor. This is a noteworthy discovery since CAR-T work to date has largely not exploited such naturally occurring mutations, while instead concentrating on those seen in the patient’s set of key tumor mutations.

As currently conceived, CAR-T, and what is being referred to more broadly as adoptive cell therapies, involves removing T cells from the patient’s body and engineering their activation, then reintroducing them back to the patient. This is laborious, technically difficult, and very expensive. Recently, the idea of achieving all of this via an injection of virus that specifically infects T cells and inserts the genes needed, was advanced by two biotech companies with preclinical results, one in non-human primates.

Gearing up to meet the challenge of solid tumor CAR-T intervention, there’s more work using CRISPR genome editing of T cell receptors. A.I. is increasingly being exploited to process the data from sequencing and identify optimal neoantigens.

Instead of just CAR-T, we’re seeing the emergence of CAR-macrophage and CAR-natural killer (NK) cells strategies, and rapidly expanding potential combinations of all the strategies I’ve mentioned. No less, there’s been maturation of on-off suicide switches programmed in, to limit cytokine release and promote safety of these interventions. Overall, major side effects of immunotherapies are not only cytokine release syndromes, but also include interstitial pneumonitis and neurotoxicity.

Summary

Given the multitude of ways cancer cells and tumor tissue can evade our immune response, durably successful treatment remains a daunting challenge. But the ingenuity of so many different approaches to unleash our immune response, and their combinations, provides considerable hope that we’ll increasingly meet the challenge in the years ahead. We have clearly learned that combining different immunotherapy strategies will be essential for many patients with the most resilient solid tumors.

Of concern, as noted by a recent editorial in The Lancet, entitled “Cancer Research Equity: Innovations For The Many, Not The Few,” is that these individualized, sophisticated strategies are not scalable; they will have limited reach and benefit. The movement towards “off the shelf” CAR-T and inexpensive, orally active checkpoint inhibitors may help mitigate this issue.

Notwithstanding this important concern, we’re seeing an array of diverse and potent immunotherapy strategies that are providing highly encouraging results, engendering more excitement than we’ve seen in this space for some time. These should propel substantial improvements in outcomes for patients in the years ahead. It can’t happen soon enough.

Thanks for reading this edition of Ground Truths. If you found it informative, please share it with your colleagues.

Dr. Topol has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for Dexcom; Illumina; Molecular Stethoscope; Quest Diagnostics; Blue Cross Blue Shield Association. Received research grant from National Institutes of Health.

A version of this article appeared on Medscape.com.

How much of societal diet-related scientific illiteracy can be blamed on the publication decisions of medical journals around food studies?

That was the question I pondered when reading “Association between kimchi consumption and obesity based on BMI and abdominal obesity in Korean adults: a cross-sectional analysis of the Health Examinees study,” recently published in BMJ Open. Although I will get to the study particulars momentarily, that it’s 2024 and journals are still publishing cross-sectional studies of the impact of a single food’s subjectively reported consumption on health outcomes is mind boggling.

You might wonder why I wasn’t mind boggled by the authors rather than the journal — but the authors’ interest in publishing a study on kimchi’s supposed impact on obesity is an easy thing to explain, in that the study was funded by the World Institute of Kimchi, where two of its four authors are employed.

You might also wonder why I wasn’t mind boggled by media running with this story — but the media’s job is to capture eyeballs, and who doesn’t love a good magic food story, doubly so for one involving obesity and one with a study backing it up?

Back to this World Institute of Kimchi project looking at kimchi intake on obesity rates. No doubt if I worked for the World Institute of Kimchi, I would want kimchi to be shown to be somehow magically protective against weight gain. So how might I go about exploring that?

Well, I could look to the data from the Health Examinees (HEXA) Study. The HEXA study was a cross-sectional look at South Koreans; included in their data collection was a 106-item food frequency questionnaire (FFQ).

That questionnaire looked at 106 food items — yep, you guessed it, explicitly including kimchi. Not included in this FFQ, though, were prepared foods, meaning that it was unable to measure seasonings, spices, or cooking oils. Also perhaps problematic is that no doubt most of us consume more than 106 total food items in our diets. Perhaps this is why the validation study of HEXA’s food item–based FFQ found that it had “relatively low validity” when compared against 12-day food diaries and why its creators themselves report it to be in their study’s conclusion only “reasonably acceptable” to apply to a population. But yes, kimchi!

So for the sake of this exercise, though, let’s assume that instead of only a reasonably acceptable FFQ with low validity, the FFQ was fantastic and its data robust. How great then is kimchi at preventing obesity? Certainly, the media report it’s pretty darn good. Here’s a smattering from the literal dozens of headlines of stories covering this paper:

Eating kimchi every day could help stave off weight gain, new study says — NBC News

Eating kimchi every day may prevent weight gain, research suggests — Sky News

Want to avoid piling on the pounds? Try kimchi for breakfast — The Telegraph

But when we turn to the paper itself, suddenly things aren’t so clear.

According to the paper, men who reported eating two to three servings of kimchi per day were found to have lower rates of obesity, whereas men who reported eating three to five servings of kimchi per day were not. But these are overlapping groups! Also found was that men consuming more than five servings of kimchi per day have higher rates of obesity. When taken together, these findings do not demonstrate a statistically significant trend of kimchi intake on obesity in men. Whereas in women, things are worse in that the more kimchi reportedly consumed, the more obesity, in a trend that did (just) reach statistical significance.

So even if we pretend the FFQs were robust enough to make conclusions about a single food’s impact on obesity, and we pretend there was a well-described, plausible mechanistic reason to believe same (there isn’t), and we pretend that this particular FFQ had better than “relatively low validity,” there is no conclusion here to be drawn about kimchi’s impact on obesity.

What we can conclude is that when it comes to publishing papers purporting to find the impact of single foods on obesity, journals will still happily publish them and their publication will lead to hyperbolic headlines and stories, which in turn reinforce the scientifically illiterate notion that the highly complex multifactorial problem of obesity boils down to simple food choices, which in turn keeps weight loss grifters everywhere in business while fueling societal weight bias.

Dr. Freedhoff is Associate Professor, Department of Family Medicine, University of Ottawa; Medical Director, Bariatric Medical Institute, Ottawa, Ontario, Canada. He disclosed ties with Bariatric Medical Institute, Constant Health, and Novo Nordisk.

A version of this article appeared on Medscape.com.

How much of societal diet-related scientific illiteracy can be blamed on the publication decisions of medical journals around food studies?

That was the question I pondered when reading “Association between kimchi consumption and obesity based on BMI and abdominal obesity in Korean adults: a cross-sectional analysis of the Health Examinees study,” recently published in BMJ Open. Although I will get to the study particulars momentarily, that it’s 2024 and journals are still publishing cross-sectional studies of the impact of a single food’s subjectively reported consumption on health outcomes is mind boggling.

You might wonder why I wasn’t mind boggled by the authors rather than the journal — but the authors’ interest in publishing a study on kimchi’s supposed impact on obesity is an easy thing to explain, in that the study was funded by the World Institute of Kimchi, where two of its four authors are employed.

You might also wonder why I wasn’t mind boggled by media running with this story — but the media’s job is to capture eyeballs, and who doesn’t love a good magic food story, doubly so for one involving obesity and one with a study backing it up?

Back to this World Institute of Kimchi project looking at kimchi intake on obesity rates. No doubt if I worked for the World Institute of Kimchi, I would want kimchi to be shown to be somehow magically protective against weight gain. So how might I go about exploring that?

Well, I could look to the data from the Health Examinees (HEXA) Study. The HEXA study was a cross-sectional look at South Koreans; included in their data collection was a 106-item food frequency questionnaire (FFQ).

That questionnaire looked at 106 food items — yep, you guessed it, explicitly including kimchi. Not included in this FFQ, though, were prepared foods, meaning that it was unable to measure seasonings, spices, or cooking oils. Also perhaps problematic is that no doubt most of us consume more than 106 total food items in our diets. Perhaps this is why the validation study of HEXA’s food item–based FFQ found that it had “relatively low validity” when compared against 12-day food diaries and why its creators themselves report it to be in their study’s conclusion only “reasonably acceptable” to apply to a population. But yes, kimchi!

So for the sake of this exercise, though, let’s assume that instead of only a reasonably acceptable FFQ with low validity, the FFQ was fantastic and its data robust. How great then is kimchi at preventing obesity? Certainly, the media report it’s pretty darn good. Here’s a smattering from the literal dozens of headlines of stories covering this paper:

Eating kimchi every day could help stave off weight gain, new study says — NBC News

Eating kimchi every day may prevent weight gain, research suggests — Sky News

Want to avoid piling on the pounds? Try kimchi for breakfast — The Telegraph

But when we turn to the paper itself, suddenly things aren’t so clear.

According to the paper, men who reported eating two to three servings of kimchi per day were found to have lower rates of obesity, whereas men who reported eating three to five servings of kimchi per day were not. But these are overlapping groups! Also found was that men consuming more than five servings of kimchi per day have higher rates of obesity. When taken together, these findings do not demonstrate a statistically significant trend of kimchi intake on obesity in men. Whereas in women, things are worse in that the more kimchi reportedly consumed, the more obesity, in a trend that did (just) reach statistical significance.

So even if we pretend the FFQs were robust enough to make conclusions about a single food’s impact on obesity, and we pretend there was a well-described, plausible mechanistic reason to believe same (there isn’t), and we pretend that this particular FFQ had better than “relatively low validity,” there is no conclusion here to be drawn about kimchi’s impact on obesity.

What we can conclude is that when it comes to publishing papers purporting to find the impact of single foods on obesity, journals will still happily publish them and their publication will lead to hyperbolic headlines and stories, which in turn reinforce the scientifically illiterate notion that the highly complex multifactorial problem of obesity boils down to simple food choices, which in turn keeps weight loss grifters everywhere in business while fueling societal weight bias.

Dr. Freedhoff is Associate Professor, Department of Family Medicine, University of Ottawa; Medical Director, Bariatric Medical Institute, Ottawa, Ontario, Canada. He disclosed ties with Bariatric Medical Institute, Constant Health, and Novo Nordisk.

A version of this article appeared on Medscape.com.

How much of societal diet-related scientific illiteracy can be blamed on the publication decisions of medical journals around food studies?

That was the question I pondered when reading “Association between kimchi consumption and obesity based on BMI and abdominal obesity in Korean adults: a cross-sectional analysis of the Health Examinees study,” recently published in BMJ Open. Although I will get to the study particulars momentarily, that it’s 2024 and journals are still publishing cross-sectional studies of the impact of a single food’s subjectively reported consumption on health outcomes is mind boggling.

You might wonder why I wasn’t mind boggled by the authors rather than the journal — but the authors’ interest in publishing a study on kimchi’s supposed impact on obesity is an easy thing to explain, in that the study was funded by the World Institute of Kimchi, where two of its four authors are employed.

You might also wonder why I wasn’t mind boggled by media running with this story — but the media’s job is to capture eyeballs, and who doesn’t love a good magic food story, doubly so for one involving obesity and one with a study backing it up?

Back to this World Institute of Kimchi project looking at kimchi intake on obesity rates. No doubt if I worked for the World Institute of Kimchi, I would want kimchi to be shown to be somehow magically protective against weight gain. So how might I go about exploring that?

Well, I could look to the data from the Health Examinees (HEXA) Study. The HEXA study was a cross-sectional look at South Koreans; included in their data collection was a 106-item food frequency questionnaire (FFQ).

That questionnaire looked at 106 food items — yep, you guessed it, explicitly including kimchi. Not included in this FFQ, though, were prepared foods, meaning that it was unable to measure seasonings, spices, or cooking oils. Also perhaps problematic is that no doubt most of us consume more than 106 total food items in our diets. Perhaps this is why the validation study of HEXA’s food item–based FFQ found that it had “relatively low validity” when compared against 12-day food diaries and why its creators themselves report it to be in their study’s conclusion only “reasonably acceptable” to apply to a population. But yes, kimchi!

So for the sake of this exercise, though, let’s assume that instead of only a reasonably acceptable FFQ with low validity, the FFQ was fantastic and its data robust. How great then is kimchi at preventing obesity? Certainly, the media report it’s pretty darn good. Here’s a smattering from the literal dozens of headlines of stories covering this paper:

Eating kimchi every day could help stave off weight gain, new study says — NBC News

Eating kimchi every day may prevent weight gain, research suggests — Sky News

Want to avoid piling on the pounds? Try kimchi for breakfast — The Telegraph

But when we turn to the paper itself, suddenly things aren’t so clear.

According to the paper, men who reported eating two to three servings of kimchi per day were found to have lower rates of obesity, whereas men who reported eating three to five servings of kimchi per day were not. But these are overlapping groups! Also found was that men consuming more than five servings of kimchi per day have higher rates of obesity. When taken together, these findings do not demonstrate a statistically significant trend of kimchi intake on obesity in men. Whereas in women, things are worse in that the more kimchi reportedly consumed, the more obesity, in a trend that did (just) reach statistical significance.

So even if we pretend the FFQs were robust enough to make conclusions about a single food’s impact on obesity, and we pretend there was a well-described, plausible mechanistic reason to believe same (there isn’t), and we pretend that this particular FFQ had better than “relatively low validity,” there is no conclusion here to be drawn about kimchi’s impact on obesity.

What we can conclude is that when it comes to publishing papers purporting to find the impact of single foods on obesity, journals will still happily publish them and their publication will lead to hyperbolic headlines and stories, which in turn reinforce the scientifically illiterate notion that the highly complex multifactorial problem of obesity boils down to simple food choices, which in turn keeps weight loss grifters everywhere in business while fueling societal weight bias.

Dr. Freedhoff is Associate Professor, Department of Family Medicine, University of Ottawa; Medical Director, Bariatric Medical Institute, Ottawa, Ontario, Canada. He disclosed ties with Bariatric Medical Institute, Constant Health, and Novo Nordisk.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

I want to briefly discuss a critically important topic that cannot be overly emphasized. It is the relevance, the importance, the benefits, and the outcome of HPV vaccination.

The paper I’m referring to was published in Pediatrics in October 2023. It’s titled, “Ten-Year Follow-up of 9-Valent Human Papillomavirus Vaccine: Immunogenicity, Effectiveness, and Safety.”

Let me emphasize that we’re talking about a 10-year follow-up. In this particular paper and analysis, 301 boys — I emphasize boys — were included and 971 girls at 40 different sites in 13 countries, who received the 9-valent vaccine, which includes HPV 16, 18, and seven other types.

These investigators demonstrated that the seropositivity rate 10 years after vaccination remained high for all nine types they looked at. Most importantly, there was not a single case. Not one. Let me repeat this: There was not a single case of high-grade intraepithelial neoplasia, or worse, or condyloma in either males or females. There was not a single case in over 1000 individuals with a follow-up of more than 10 years.

It is difficult to overstate the magnitude of the benefit associated with HPV vaccination for our children and young adults on their risk of developing highly relevant, life-changing, potentially deadly cancers.

For those of you who are interested in this topic — which should include almost all of you, if not all of you — I encourage you to read this very important follow-up paper, again, demonstrating the simple, overwhelming magnitude of the benefit of HPV vaccination. I thank you for your attention.
 

Dr. Markman is a professor in the department of medical oncology and therapeutics research, City of Hope, Duarte, California, and president of medicine and science, City of Hope Atlanta, Chicago, and Phoenix. He disclosed ties with GlaxoSmithKline; AstraZeneca.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

I want to briefly discuss a critically important topic that cannot be overly emphasized. It is the relevance, the importance, the benefits, and the outcome of HPV vaccination.

The paper I’m referring to was published in Pediatrics in October 2023. It’s titled, “Ten-Year Follow-up of 9-Valent Human Papillomavirus Vaccine: Immunogenicity, Effectiveness, and Safety.”

Let me emphasize that we’re talking about a 10-year follow-up. In this particular paper and analysis, 301 boys — I emphasize boys — were included and 971 girls at 40 different sites in 13 countries, who received the 9-valent vaccine, which includes HPV 16, 18, and seven other types.

These investigators demonstrated that the seropositivity rate 10 years after vaccination remained high for all nine types they looked at. Most importantly, there was not a single case. Not one. Let me repeat this: There was not a single case of high-grade intraepithelial neoplasia, or worse, or condyloma in either males or females. There was not a single case in over 1000 individuals with a follow-up of more than 10 years.

It is difficult to overstate the magnitude of the benefit associated with HPV vaccination for our children and young adults on their risk of developing highly relevant, life-changing, potentially deadly cancers.

For those of you who are interested in this topic — which should include almost all of you, if not all of you — I encourage you to read this very important follow-up paper, again, demonstrating the simple, overwhelming magnitude of the benefit of HPV vaccination. I thank you for your attention.
 

Dr. Markman is a professor in the department of medical oncology and therapeutics research, City of Hope, Duarte, California, and president of medicine and science, City of Hope Atlanta, Chicago, and Phoenix. He disclosed ties with GlaxoSmithKline; AstraZeneca.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

I want to briefly discuss a critically important topic that cannot be overly emphasized. It is the relevance, the importance, the benefits, and the outcome of HPV vaccination.

The paper I’m referring to was published in Pediatrics in October 2023. It’s titled, “Ten-Year Follow-up of 9-Valent Human Papillomavirus Vaccine: Immunogenicity, Effectiveness, and Safety.”

Let me emphasize that we’re talking about a 10-year follow-up. In this particular paper and analysis, 301 boys — I emphasize boys — were included and 971 girls at 40 different sites in 13 countries, who received the 9-valent vaccine, which includes HPV 16, 18, and seven other types.

These investigators demonstrated that the seropositivity rate 10 years after vaccination remained high for all nine types they looked at. Most importantly, there was not a single case. Not one. Let me repeat this: There was not a single case of high-grade intraepithelial neoplasia, or worse, or condyloma in either males or females. There was not a single case in over 1000 individuals with a follow-up of more than 10 years.

It is difficult to overstate the magnitude of the benefit associated with HPV vaccination for our children and young adults on their risk of developing highly relevant, life-changing, potentially deadly cancers.

For those of you who are interested in this topic — which should include almost all of you, if not all of you — I encourage you to read this very important follow-up paper, again, demonstrating the simple, overwhelming magnitude of the benefit of HPV vaccination. I thank you for your attention.
 

Dr. Markman is a professor in the department of medical oncology and therapeutics research, City of Hope, Duarte, California, and president of medicine and science, City of Hope Atlanta, Chicago, and Phoenix. He disclosed ties with GlaxoSmithKline; AstraZeneca.

A version of this article appeared on Medscape.com.

I recently wrote about a fledgling program here in Maine in which some emergency room physicians were being outfitted with equipment and communications gear that would allow them to respond on the fly to emergencies in the field when they weren’t working in the hospital. I questioned the rationale of using in-house personnel, already in short supply, for the few situations in which trained EMT personnel would usually be called. At the same time, I promised to return to the broader subject of the role of physicians as first responders in a future letter. And, here it is.

Have you ever been on a plane or at a large public gathering and the public addressed system crackled, “Is there a doctor on board” or in the audience? Or have you been on the highway and come upon a fresh accident in which it appears that there may have been injuries? Or at a youth soccer game in which a player has been injured and is still on the ground?

How do you usually respond in situations like this? Do you immediately identify yourself as a physician? Or, do you routinely shy away from involvement? What thoughts run through your head?

Do you feel your training and experience with emergencies is so outdated that you doubt you could be of any assistance? Has your practice become so specialized that you aren’t comfortable with anything outside of your specialty? Maybe getting involved is likely to throw your already tight travel schedule into disarray? Or are you afraid that should something go wrong while you were helping out you could be sued?

Keeping in mind that I am a retired septuagenarian pediatrician more than a decade removed from active practice, I would describe my usual response to these situations as “attentive hovering.” I position myself to have a good view of the victim and watch to see if there are any other responders. Either because of their personality or their experience, often there is someone who steps forward to help. Trained EMTs seem to have no hesitancy going into action. If I sense things aren’t going well, or the victim is a child, I will identify myself as a retired pediatrician and offer my assistance. Even if the response given by others seems appropriate, I may still eventually identify myself, maybe to lend an air of legitimacy to the process.

What are the roots of my hesitancy? I have found that I generally have little to add when there is a trained first responder on hand. They have been-there-and-done-that far more recently than I have. They know how to stabilize potential or obvious fractures. They know how to position the victim for transport. Even when I am in an environment where my medical background is already known, I yield to the more recently experienced first responders.

I don’t particularly worry about being sued. Every state has Good Samaritan laws. Although the laws vary from state to state, here in Maine I feel comfortable with the good sense of my fellow citizens. I understand if you live or practice in a more litigious environment you may be more concerned. On an airplane there is the Aviation Medical Assistant Act, which became law in 1998, and provides us with some extra protection.

What if there is a situation in which even with my outdated skills I seem to be the only show in town? Fortunately, that situation hasn’t occurred for me in quite a few years, but the odds are that one might occur. In almost 1 out of 600 airline flights, there is an inflight emergency. I tend to hang out with other septuagenarians and octogenarians doing active things. And I frequent youth athletic events where there is unlikely to be a first responder assigned to the event.

Should I be doing more to update my skills? It’s been a while since I refreshed by CPR techniques. I can’t recall the last time I handled a defibrillator. Should I be learning more about exsanguination prevention techniques?

Every so often there are some rumblings to mandate that all physicians should be required to update these first responder skills to maintain their license or certification. That wouldn’t cover those of us who are retired or who no longer practice medicine. And, I’m not sure we need to add another layer to the system. I think there are enough of us out there who would like to add ourselves to the first responder population, maybe not as fully trained experts but as folks who would like to be more ready to help by updating old or seldom-used skills.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

I recently wrote about a fledgling program here in Maine in which some emergency room physicians were being outfitted with equipment and communications gear that would allow them to respond on the fly to emergencies in the field when they weren’t working in the hospital. I questioned the rationale of using in-house personnel, already in short supply, for the few situations in which trained EMT personnel would usually be called. At the same time, I promised to return to the broader subject of the role of physicians as first responders in a future letter. And, here it is.

Have you ever been on a plane or at a large public gathering and the public addressed system crackled, “Is there a doctor on board” or in the audience? Or have you been on the highway and come upon a fresh accident in which it appears that there may have been injuries? Or at a youth soccer game in which a player has been injured and is still on the ground?

How do you usually respond in situations like this? Do you immediately identify yourself as a physician? Or, do you routinely shy away from involvement? What thoughts run through your head?

Do you feel your training and experience with emergencies is so outdated that you doubt you could be of any assistance? Has your practice become so specialized that you aren’t comfortable with anything outside of your specialty? Maybe getting involved is likely to throw your already tight travel schedule into disarray? Or are you afraid that should something go wrong while you were helping out you could be sued?

Keeping in mind that I am a retired septuagenarian pediatrician more than a decade removed from active practice, I would describe my usual response to these situations as “attentive hovering.” I position myself to have a good view of the victim and watch to see if there are any other responders. Either because of their personality or their experience, often there is someone who steps forward to help. Trained EMTs seem to have no hesitancy going into action. If I sense things aren’t going well, or the victim is a child, I will identify myself as a retired pediatrician and offer my assistance. Even if the response given by others seems appropriate, I may still eventually identify myself, maybe to lend an air of legitimacy to the process.

What are the roots of my hesitancy? I have found that I generally have little to add when there is a trained first responder on hand. They have been-there-and-done-that far more recently than I have. They know how to stabilize potential or obvious fractures. They know how to position the victim for transport. Even when I am in an environment where my medical background is already known, I yield to the more recently experienced first responders.

I don’t particularly worry about being sued. Every state has Good Samaritan laws. Although the laws vary from state to state, here in Maine I feel comfortable with the good sense of my fellow citizens. I understand if you live or practice in a more litigious environment you may be more concerned. On an airplane there is the Aviation Medical Assistant Act, which became law in 1998, and provides us with some extra protection.

What if there is a situation in which even with my outdated skills I seem to be the only show in town? Fortunately, that situation hasn’t occurred for me in quite a few years, but the odds are that one might occur. In almost 1 out of 600 airline flights, there is an inflight emergency. I tend to hang out with other septuagenarians and octogenarians doing active things. And I frequent youth athletic events where there is unlikely to be a first responder assigned to the event.

Should I be doing more to update my skills? It’s been a while since I refreshed by CPR techniques. I can’t recall the last time I handled a defibrillator. Should I be learning more about exsanguination prevention techniques?

Every so often there are some rumblings to mandate that all physicians should be required to update these first responder skills to maintain their license or certification. That wouldn’t cover those of us who are retired or who no longer practice medicine. And, I’m not sure we need to add another layer to the system. I think there are enough of us out there who would like to add ourselves to the first responder population, maybe not as fully trained experts but as folks who would like to be more ready to help by updating old or seldom-used skills.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

I recently wrote about a fledgling program here in Maine in which some emergency room physicians were being outfitted with equipment and communications gear that would allow them to respond on the fly to emergencies in the field when they weren’t working in the hospital. I questioned the rationale of using in-house personnel, already in short supply, for the few situations in which trained EMT personnel would usually be called. At the same time, I promised to return to the broader subject of the role of physicians as first responders in a future letter. And, here it is.

Have you ever been on a plane or at a large public gathering and the public addressed system crackled, “Is there a doctor on board” or in the audience? Or have you been on the highway and come upon a fresh accident in which it appears that there may have been injuries? Or at a youth soccer game in which a player has been injured and is still on the ground?

How do you usually respond in situations like this? Do you immediately identify yourself as a physician? Or, do you routinely shy away from involvement? What thoughts run through your head?

Do you feel your training and experience with emergencies is so outdated that you doubt you could be of any assistance? Has your practice become so specialized that you aren’t comfortable with anything outside of your specialty? Maybe getting involved is likely to throw your already tight travel schedule into disarray? Or are you afraid that should something go wrong while you were helping out you could be sued?

Keeping in mind that I am a retired septuagenarian pediatrician more than a decade removed from active practice, I would describe my usual response to these situations as “attentive hovering.” I position myself to have a good view of the victim and watch to see if there are any other responders. Either because of their personality or their experience, often there is someone who steps forward to help. Trained EMTs seem to have no hesitancy going into action. If I sense things aren’t going well, or the victim is a child, I will identify myself as a retired pediatrician and offer my assistance. Even if the response given by others seems appropriate, I may still eventually identify myself, maybe to lend an air of legitimacy to the process.

What are the roots of my hesitancy? I have found that I generally have little to add when there is a trained first responder on hand. They have been-there-and-done-that far more recently than I have. They know how to stabilize potential or obvious fractures. They know how to position the victim for transport. Even when I am in an environment where my medical background is already known, I yield to the more recently experienced first responders.

I don’t particularly worry about being sued. Every state has Good Samaritan laws. Although the laws vary from state to state, here in Maine I feel comfortable with the good sense of my fellow citizens. I understand if you live or practice in a more litigious environment you may be more concerned. On an airplane there is the Aviation Medical Assistant Act, which became law in 1998, and provides us with some extra protection.

What if there is a situation in which even with my outdated skills I seem to be the only show in town? Fortunately, that situation hasn’t occurred for me in quite a few years, but the odds are that one might occur. In almost 1 out of 600 airline flights, there is an inflight emergency. I tend to hang out with other septuagenarians and octogenarians doing active things. And I frequent youth athletic events where there is unlikely to be a first responder assigned to the event.

Should I be doing more to update my skills? It’s been a while since I refreshed by CPR techniques. I can’t recall the last time I handled a defibrillator. Should I be learning more about exsanguination prevention techniques?

Every so often there are some rumblings to mandate that all physicians should be required to update these first responder skills to maintain their license or certification. That wouldn’t cover those of us who are retired or who no longer practice medicine. And, I’m not sure we need to add another layer to the system. I think there are enough of us out there who would like to add ourselves to the first responder population, maybe not as fully trained experts but as folks who would like to be more ready to help by updating old or seldom-used skills.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

“You’ll never walk alone.” — Nettie Fowler, Carousel

A few winters ago, a young man and his fiancée were driving on the 91 freeway in southern California during a torrential downpour when their Honda Civic hydroplaned, slamming into the jersey barrier. They were both unhurt. Unsure what to do next, they made the catastrophic decision to exit the vehicle. As the man walked around the back of the car he was nearly hit by a black sedan sliding out of control trying to avoid them. When he came around the car, his fiancé was nowhere to be found. She had been struck at highway speed and lay crushed under the sedan hundreds of feet away.

I know this poor man because he was referred to me. Not as a dermatologist, but as a fellow human healing from trauma. On January 1, 2019, at about 9:30 PM, while we were home together, my beloved wife of 24 years took her own life. Even 5 years on it is difficult to believe that she isn’t proofing this paragraph like she had done for every one of my Derm News columns for years. We had been together since teenagers and had lived a joy-filled life. As anyone who has lost a loved one to suicide knows, it is an unknowable, fatal disease. Very few of my patients know my story. There isn’t any medical reason to share. But that day I joined the community of those who have carried unbearable heaviness of grief and survived. Sometimes others seek me out for help.

Kaiser Permanente

At first, my instinct was to guide them, to give advice, to tell them what to do and where to go. But I’ve learned that people in this dark valley don’t need a guide. They need someone to accompany them. To walk with them for a few minutes on their lonely journey. I recently read David Brooks’s new book, How to Know a Person. I’ve been a fan of his since he joined the New York Times in 2003 and have read almost everything he’s written. I sometimes even imagine how he might approach a column whenever I’m stuck (thank you, David). His The Road to Character book is in my canon of literature for self-growth. This latest book is an interesting digression from that central theme. He argues that our society is in acute need of forming better connections and that an important way we can be moral is to learn, and to practice, how to know each other. He shares an emotional experience of losing a close friend to suicide and writes a poignant explanation of what it means to accompany someone in need. It particularly resonated with me. We are doctors and are wired to find the source of a problem, like quickly rotating through the 4X, 10X, 40X on a microscope. Once identified, we spend most of our time creating and explaining treatments. I see how this makes me a great dermatologist but just an average human.

Brooks tells the story of a woman with a brain tumor who often finds herself on the ground surrounded by well-meaning people trying to help. She explains later that what she really needs in those moments is just for someone to get on the ground and lie with her. To accompany her.

Having crossed the midpoint of life, I see with the benefit of perspective how suffering has afforded me wisdom: I am more sensitive and attuned to others. It also gave me credibility: I know how it feels to walk life’s loneliest journey. I’ve also learned to make myself vulnerable for someone to share their story with me. I won’t be afraid to hear the details. I won’t judge them for weeping too little or for sobbing too much. I don’t answer whys. I won’t say what they should do next. But for a few minutes I can walk beside them as a person who cares.

Courtesy Jeffrey Benabio, MD

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on X. Write to him at [email protected].

“You’ll never walk alone.” — Nettie Fowler, Carousel

A few winters ago, a young man and his fiancée were driving on the 91 freeway in southern California during a torrential downpour when their Honda Civic hydroplaned, slamming into the jersey barrier. They were both unhurt. Unsure what to do next, they made the catastrophic decision to exit the vehicle. As the man walked around the back of the car he was nearly hit by a black sedan sliding out of control trying to avoid them. When he came around the car, his fiancé was nowhere to be found. She had been struck at highway speed and lay crushed under the sedan hundreds of feet away.

I know this poor man because he was referred to me. Not as a dermatologist, but as a fellow human healing from trauma. On January 1, 2019, at about 9:30 PM, while we were home together, my beloved wife of 24 years took her own life. Even 5 years on it is difficult to believe that she isn’t proofing this paragraph like she had done for every one of my Derm News columns for years. We had been together since teenagers and had lived a joy-filled life. As anyone who has lost a loved one to suicide knows, it is an unknowable, fatal disease. Very few of my patients know my story. There isn’t any medical reason to share. But that day I joined the community of those who have carried unbearable heaviness of grief and survived. Sometimes others seek me out for help.

Kaiser Permanente

At first, my instinct was to guide them, to give advice, to tell them what to do and where to go. But I’ve learned that people in this dark valley don’t need a guide. They need someone to accompany them. To walk with them for a few minutes on their lonely journey. I recently read David Brooks’s new book, How to Know a Person. I’ve been a fan of his since he joined the New York Times in 2003 and have read almost everything he’s written. I sometimes even imagine how he might approach a column whenever I’m stuck (thank you, David). His The Road to Character book is in my canon of literature for self-growth. This latest book is an interesting digression from that central theme. He argues that our society is in acute need of forming better connections and that an important way we can be moral is to learn, and to practice, how to know each other. He shares an emotional experience of losing a close friend to suicide and writes a poignant explanation of what it means to accompany someone in need. It particularly resonated with me. We are doctors and are wired to find the source of a problem, like quickly rotating through the 4X, 10X, 40X on a microscope. Once identified, we spend most of our time creating and explaining treatments. I see how this makes me a great dermatologist but just an average human.

Brooks tells the story of a woman with a brain tumor who often finds herself on the ground surrounded by well-meaning people trying to help. She explains later that what she really needs in those moments is just for someone to get on the ground and lie with her. To accompany her.

Having crossed the midpoint of life, I see with the benefit of perspective how suffering has afforded me wisdom: I am more sensitive and attuned to others. It also gave me credibility: I know how it feels to walk life’s loneliest journey. I’ve also learned to make myself vulnerable for someone to share their story with me. I won’t be afraid to hear the details. I won’t judge them for weeping too little or for sobbing too much. I don’t answer whys. I won’t say what they should do next. But for a few minutes I can walk beside them as a person who cares.

Courtesy Jeffrey Benabio, MD

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on X. Write to him at [email protected].

“You’ll never walk alone.” — Nettie Fowler, Carousel

A few winters ago, a young man and his fiancée were driving on the 91 freeway in southern California during a torrential downpour when their Honda Civic hydroplaned, slamming into the jersey barrier. They were both unhurt. Unsure what to do next, they made the catastrophic decision to exit the vehicle. As the man walked around the back of the car he was nearly hit by a black sedan sliding out of control trying to avoid them. When he came around the car, his fiancé was nowhere to be found. She had been struck at highway speed and lay crushed under the sedan hundreds of feet away.

I know this poor man because he was referred to me. Not as a dermatologist, but as a fellow human healing from trauma. On January 1, 2019, at about 9:30 PM, while we were home together, my beloved wife of 24 years took her own life. Even 5 years on it is difficult to believe that she isn’t proofing this paragraph like she had done for every one of my Derm News columns for years. We had been together since teenagers and had lived a joy-filled life. As anyone who has lost a loved one to suicide knows, it is an unknowable, fatal disease. Very few of my patients know my story. There isn’t any medical reason to share. But that day I joined the community of those who have carried unbearable heaviness of grief and survived. Sometimes others seek me out for help.

Kaiser Permanente

At first, my instinct was to guide them, to give advice, to tell them what to do and where to go. But I’ve learned that people in this dark valley don’t need a guide. They need someone to accompany them. To walk with them for a few minutes on their lonely journey. I recently read David Brooks’s new book, How to Know a Person. I’ve been a fan of his since he joined the New York Times in 2003 and have read almost everything he’s written. I sometimes even imagine how he might approach a column whenever I’m stuck (thank you, David). His The Road to Character book is in my canon of literature for self-growth. This latest book is an interesting digression from that central theme. He argues that our society is in acute need of forming better connections and that an important way we can be moral is to learn, and to practice, how to know each other. He shares an emotional experience of losing a close friend to suicide and writes a poignant explanation of what it means to accompany someone in need. It particularly resonated with me. We are doctors and are wired to find the source of a problem, like quickly rotating through the 4X, 10X, 40X on a microscope. Once identified, we spend most of our time creating and explaining treatments. I see how this makes me a great dermatologist but just an average human.

Brooks tells the story of a woman with a brain tumor who often finds herself on the ground surrounded by well-meaning people trying to help. She explains later that what she really needs in those moments is just for someone to get on the ground and lie with her. To accompany her.

Having crossed the midpoint of life, I see with the benefit of perspective how suffering has afforded me wisdom: I am more sensitive and attuned to others. It also gave me credibility: I know how it feels to walk life’s loneliest journey. I’ve also learned to make myself vulnerable for someone to share their story with me. I won’t be afraid to hear the details. I won’t judge them for weeping too little or for sobbing too much. I don’t answer whys. I won’t say what they should do next. But for a few minutes I can walk beside them as a person who cares.

Courtesy Jeffrey Benabio, MD

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on X. Write to him at [email protected].

This patient showed no evidence of recurrence in the scar where the melanoma was excised, and had no enlarged lymph nodes on palpation. His complete blood count and liver function tests were normal. A positron emission tomography (PET) scan was ordered by Dr. Nasser that revealed hypermetabolic right paratracheal, right hilar, and subcarinal lymph nodes, highly suspicious for malignant lymph nodes. The patient was referred to oncology for metastatic melanoma treatment and has been doing well on ipilimumab and nivolumab.

Courtesy Lucas Shapiro and Dr. Natalie Y. Nasser

Vitiligo is an autoimmune condition characterized by the progressive destruction of melanocytes resulting in hypopigmentation or depigmentation of the skin. Vitiligo has been associated with cutaneous melanoma. Patients with melanoma can present with hypopigmentation around the primary lesion and/or bilateral symmetrical lesions similar to vitiligo. Melanoma-associated leukoderma occurs in a portion of patients with melanoma and is correlated with a favorable prognosis. Additionally, leukoderma has been described as a side effect of melanoma treatment itself. However, cases such as this one have also been reported of vitiligo-like depigmentation presenting prior to the diagnosis of metastatic melanoma.

Melanoma, like vitiligo, is considered highly immunogenic, and cytotoxic T lymphocytes (CTLs) can recognize antigens in melanoma. Furthermore, studies have shown a vitiligo-like halo around melanoma tumors, likely caused by T-cell recruitment, and this may lead to tumor destruction, but rarely total clearance. It seems that the CTL infiltrate in both diseases is similar, but regulatory T cells are decreased in vitiligo, whereas they are present in melanomas and may contribute to the immunosuppressive tumor microenvironment found at the margin of these lesions.

Leukoderma is also associated with melanoma immunotherapy which may be described as drug-induced leukoderma. Additionally, the frequency of recognition of melanoma cells by CTLs leading to hypopigmentation appears to be higher in those with metastatic disease. High immune infiltrate with CTLs and interferon-gamma (IFN-gamma) expression by type 1 T helper cells is associated with favorable prognosis. Immunotherapy with checkpoint inhibitors has shown promise in treatment augmentation for melanoma, but not all patients fully respond to therapy. Nonetheless, development of leukoderma with these treatments has been significantly associated with good therapeutic response. Depigmentation of hair and retinal epithelium has also been reported. However, drug-induced leukoderma and vitiligo seem to have clinical and biological differences, including family history of disease and serum chemokine levels. Vaccines are in production to aid in the treatment of melanoma, but researchers must first identify the appropriate antigen(s) to include.

Conversely, vitiligo-like depigmentation has been reported as a harbinger of metastatic melanoma. Patients with previous excision of primary melanoma have presented months or years later with depigmentation and, upon further evaluation, have been diagnosed with metastatic melanoma. The prevalence of depigmentation in melanoma patients is about 3%-6%, and is estimated to be 7-10 times more common in those with melanoma than in the general population. In most cases, hypopigmentation follows the diagnosis of melanoma, with an average of 4.8 years after the initial diagnosis and 1-2 years after lymph node or distant metastases. It is unclear whether hypopigmentation occurs before or after the growth of metastatic lesions, but this clinical finding in a patient with previous melanoma may serve as an important clue to conduct further investigation for metastasis.

This case and the photos were submitted by Lucas Shapiro, BS, of Nova Southeastern University College of Osteopathic Medicine, Fort Lauderdale, Florida, and Natalie Y. Nasser, MD, Kaiser Permanente Riverside Medical Center; Riverside, California. The column was edited by Donna Bilu Martin, MD.
 

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Florida More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

References

Cerci FB et al. Cutis. 2017 Jun;99(6):E1-E2. PMID: 28686764.

Cho EA et al. Ann Dermatol. 2009 May;21(2):178-181.

Failla CM et al. Int J Mol Sci. 2019 Nov 15;20(22):5731.

This patient showed no evidence of recurrence in the scar where the melanoma was excised, and had no enlarged lymph nodes on palpation. His complete blood count and liver function tests were normal. A positron emission tomography (PET) scan was ordered by Dr. Nasser that revealed hypermetabolic right paratracheal, right hilar, and subcarinal lymph nodes, highly suspicious for malignant lymph nodes. The patient was referred to oncology for metastatic melanoma treatment and has been doing well on ipilimumab and nivolumab.

Courtesy Lucas Shapiro and Dr. Natalie Y. Nasser

Vitiligo is an autoimmune condition characterized by the progressive destruction of melanocytes resulting in hypopigmentation or depigmentation of the skin. Vitiligo has been associated with cutaneous melanoma. Patients with melanoma can present with hypopigmentation around the primary lesion and/or bilateral symmetrical lesions similar to vitiligo. Melanoma-associated leukoderma occurs in a portion of patients with melanoma and is correlated with a favorable prognosis. Additionally, leukoderma has been described as a side effect of melanoma treatment itself. However, cases such as this one have also been reported of vitiligo-like depigmentation presenting prior to the diagnosis of metastatic melanoma.

Melanoma, like vitiligo, is considered highly immunogenic, and cytotoxic T lymphocytes (CTLs) can recognize antigens in melanoma. Furthermore, studies have shown a vitiligo-like halo around melanoma tumors, likely caused by T-cell recruitment, and this may lead to tumor destruction, but rarely total clearance. It seems that the CTL infiltrate in both diseases is similar, but regulatory T cells are decreased in vitiligo, whereas they are present in melanomas and may contribute to the immunosuppressive tumor microenvironment found at the margin of these lesions.

Leukoderma is also associated with melanoma immunotherapy which may be described as drug-induced leukoderma. Additionally, the frequency of recognition of melanoma cells by CTLs leading to hypopigmentation appears to be higher in those with metastatic disease. High immune infiltrate with CTLs and interferon-gamma (IFN-gamma) expression by type 1 T helper cells is associated with favorable prognosis. Immunotherapy with checkpoint inhibitors has shown promise in treatment augmentation for melanoma, but not all patients fully respond to therapy. Nonetheless, development of leukoderma with these treatments has been significantly associated with good therapeutic response. Depigmentation of hair and retinal epithelium has also been reported. However, drug-induced leukoderma and vitiligo seem to have clinical and biological differences, including family history of disease and serum chemokine levels. Vaccines are in production to aid in the treatment of melanoma, but researchers must first identify the appropriate antigen(s) to include.

Conversely, vitiligo-like depigmentation has been reported as a harbinger of metastatic melanoma. Patients with previous excision of primary melanoma have presented months or years later with depigmentation and, upon further evaluation, have been diagnosed with metastatic melanoma. The prevalence of depigmentation in melanoma patients is about 3%-6%, and is estimated to be 7-10 times more common in those with melanoma than in the general population. In most cases, hypopigmentation follows the diagnosis of melanoma, with an average of 4.8 years after the initial diagnosis and 1-2 years after lymph node or distant metastases. It is unclear whether hypopigmentation occurs before or after the growth of metastatic lesions, but this clinical finding in a patient with previous melanoma may serve as an important clue to conduct further investigation for metastasis.

This case and the photos were submitted by Lucas Shapiro, BS, of Nova Southeastern University College of Osteopathic Medicine, Fort Lauderdale, Florida, and Natalie Y. Nasser, MD, Kaiser Permanente Riverside Medical Center; Riverside, California. The column was edited by Donna Bilu Martin, MD.
 

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Florida More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

References

Cerci FB et al. Cutis. 2017 Jun;99(6):E1-E2. PMID: 28686764.

Cho EA et al. Ann Dermatol. 2009 May;21(2):178-181.

Failla CM et al. Int J Mol Sci. 2019 Nov 15;20(22):5731.

This patient showed no evidence of recurrence in the scar where the melanoma was excised, and had no enlarged lymph nodes on palpation. His complete blood count and liver function tests were normal. A positron emission tomography (PET) scan was ordered by Dr. Nasser that revealed hypermetabolic right paratracheal, right hilar, and subcarinal lymph nodes, highly suspicious for malignant lymph nodes. The patient was referred to oncology for metastatic melanoma treatment and has been doing well on ipilimumab and nivolumab.

Courtesy Lucas Shapiro and Dr. Natalie Y. Nasser

Vitiligo is an autoimmune condition characterized by the progressive destruction of melanocytes resulting in hypopigmentation or depigmentation of the skin. Vitiligo has been associated with cutaneous melanoma. Patients with melanoma can present with hypopigmentation around the primary lesion and/or bilateral symmetrical lesions similar to vitiligo. Melanoma-associated leukoderma occurs in a portion of patients with melanoma and is correlated with a favorable prognosis. Additionally, leukoderma has been described as a side effect of melanoma treatment itself. However, cases such as this one have also been reported of vitiligo-like depigmentation presenting prior to the diagnosis of metastatic melanoma.

Melanoma, like vitiligo, is considered highly immunogenic, and cytotoxic T lymphocytes (CTLs) can recognize antigens in melanoma. Furthermore, studies have shown a vitiligo-like halo around melanoma tumors, likely caused by T-cell recruitment, and this may lead to tumor destruction, but rarely total clearance. It seems that the CTL infiltrate in both diseases is similar, but regulatory T cells are decreased in vitiligo, whereas they are present in melanomas and may contribute to the immunosuppressive tumor microenvironment found at the margin of these lesions.

Leukoderma is also associated with melanoma immunotherapy which may be described as drug-induced leukoderma. Additionally, the frequency of recognition of melanoma cells by CTLs leading to hypopigmentation appears to be higher in those with metastatic disease. High immune infiltrate with CTLs and interferon-gamma (IFN-gamma) expression by type 1 T helper cells is associated with favorable prognosis. Immunotherapy with checkpoint inhibitors has shown promise in treatment augmentation for melanoma, but not all patients fully respond to therapy. Nonetheless, development of leukoderma with these treatments has been significantly associated with good therapeutic response. Depigmentation of hair and retinal epithelium has also been reported. However, drug-induced leukoderma and vitiligo seem to have clinical and biological differences, including family history of disease and serum chemokine levels. Vaccines are in production to aid in the treatment of melanoma, but researchers must first identify the appropriate antigen(s) to include.

Conversely, vitiligo-like depigmentation has been reported as a harbinger of metastatic melanoma. Patients with previous excision of primary melanoma have presented months or years later with depigmentation and, upon further evaluation, have been diagnosed with metastatic melanoma. The prevalence of depigmentation in melanoma patients is about 3%-6%, and is estimated to be 7-10 times more common in those with melanoma than in the general population. In most cases, hypopigmentation follows the diagnosis of melanoma, with an average of 4.8 years after the initial diagnosis and 1-2 years after lymph node or distant metastases. It is unclear whether hypopigmentation occurs before or after the growth of metastatic lesions, but this clinical finding in a patient with previous melanoma may serve as an important clue to conduct further investigation for metastasis.

This case and the photos were submitted by Lucas Shapiro, BS, of Nova Southeastern University College of Osteopathic Medicine, Fort Lauderdale, Florida, and Natalie Y. Nasser, MD, Kaiser Permanente Riverside Medical Center; Riverside, California. The column was edited by Donna Bilu Martin, MD.
 

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Florida More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

References

Cerci FB et al. Cutis. 2017 Jun;99(6):E1-E2. PMID: 28686764.

Cho EA et al. Ann Dermatol. 2009 May;21(2):178-181.

Failla CM et al. Int J Mol Sci. 2019 Nov 15;20(22):5731.

Many infants have experienced an episode of apnea, defined as a pause in respiration of 20 seconds or more. Most episodes remain unexplained, and no underlying cause can be found. Historically, these were referred to as “near-miss SIDS,” episodes, but that label suggested that all of these events would have ended in death had someone not intervened. New descriptive terminology was needed.

In the mid-1980s, the term “apparent life-threatening event” (ALTE) was adopted. But that term, too, was an overstatement, because although scary for parents, these brief apnea episodes were not, in most cases, truly life-threatening.

In 2013, authors of a systematic review coined the term “brief resolved unexplained event” (BRUE). This review also addressed the history and physical exam features associated with risk for a subsequent episode. It was felt that hospitalization and testing might be warranted if certain infants could be identified as high risk for recurrence.

What Is Considered a BRUE?

In the current working definition of BRUE, the child must be < 1 year old. The episode must be a sudden, brief, and resolved, with one or more of these characteristics:

• Cyanosis or pallor (but not turning red)
• A change in breathing (absent, decreased, or irregular)
• A change in tone (hypertonia or hypotonia)
• A change in responsiveness.

Furthermore, to qualify as a BRUE, no explanation can be found for the event based on the history and physical examination but before any laboratory testing is done. The definition also excludes children with known potential explanatory diagnoses (such as gastroesophageal reflux or bronchiolitis) and those who are otherwise symptomatically ill at the time of the event.
 

Decision to Admit and Recurrence Risk

An apnea event in an otherwise healthy infant, regardless of what it’s called, puts providers and parents in a difficult position. Should the infant be hospitalized for further monitoring and potentially more invasive testing to determine the cause of the episode? And what are the chances that the episode will be repeated?

A clinical practice guideline (CPG) for BRUE, widely adopted in 2016, resulted in significant reductions in healthcare utilization. The CPG attempted to identify low-risk infants who could safely be discharged from the emergency department. Although the CPG improved outcomes, experts acknowledged that an underlying problem was not likely to be identified even among infants deemed high risk, and these infants would be hospitalized unnecessarily.

Available data were simply insufficient to support this decision. So, with the goal of identifying factors that could help predict recurrent BRUE risk, a 15-hospital collaborative study was undertaken, followed by the development and validation of a clinical decision rule for predicting the risk for a serious underlying diagnosis or event recurrence among infants presenting with BRUE.

Here’s what we learned from more than 3000 cases of BRUE.

First, it turns out that it’s not easy to determine whether an infant is at low or high risk for recurrence of BRUE. Initially, 91.5% of patients enrolled in the study would have been labeled high risk.

Furthermore, a BRUE recurred in 14.3% of the cohort, and 4.8% of high-risk infants were found to have a serious undiagnosed condition. Seizures, airway anomalies, and gastroesophageal reflux were the top three causes of BRUE, but the spectrum of underlying pathology was quite considerable.

The problem was that 4.6% of the entire cohort were found to have a serious underlying condition, nearly identical to the proportion of high-risk infants with these conditions. This prompted the question of whether simply labeling infants “high risk” was really appropriate any longer. 
 

Revised BRUE Management

Although it hasn’t been possible to group infants neatly in low and high-risk categories, the data from that large cohort led to the development of the BRUE 2.0 criteria, which enabled more focused risk assessment of an infant who experienced a BRUE. With an app on MDCalc, these criteria allow providers to ascertain, and show families, a visual representation of their infant’s individualized risk for a subsequent BRUE and of having a serious underlying condition.

The cohort study also identified red flags from the history or physical exam of infants who experienced a BRUE: weight loss, failure to thrive, or a history of feeding problems. Exam findings such as a bulging fontanelle, forceful or bilious emesis, and evidence of gastrointestinal (GI) bleeding suggest a medical diagnosis rather than a BRUE. If GI-related causes are high on the differential, a feeding evaluation can be helpful. A feeding evaluation can be done in the outpatient setting and does not require hospitalization.

For suspicion of an underlying neurological condition (such as seizures), experts recommend obtaining a short EEG, which is highly sensitive for detecting infantile spasms and encephalopathy. They recommend reserving MRI for infants with abnormalities on EEG or physical exam. Metabolic or genetic testing should be done only if the infant looks ill, because most patients with genetic or inborn errors of metabolism will continue to have symptoms as they become older.

The approach to BRUE has moved into the realm of shared decision-making with families. The likelihood of identifying a serious diagnosis is low for most of these children. And unfortunately, no single test can diagnose the full spectrum of potential explanatory diagnoses. For example, data from 2023 demonstrate that only 1.1% of lab tests following a BRUE contributed to a diagnosis, and most of the time that was a positive viral test. Similarly, imaging was helpful in only 1.5% of cases. So, explaining the evidence and deciding along with parents what is reasonable to do (or not do) is the current state of affairs.
 

My Take

As I reflect back on two and a half decades of caring for these patients, I believe that recent data have helped us a great deal. We do less testing and admit fewer infants to the hospital than we did 20 years ago, and that’s a good thing. Nevertheless, looking for a few red flags, having a high index of suspicion when the clinical exam is abnormal, and engaging in shared decision-making with families can help make the caring for these challenging patients more bearable and lead to better outcomes for all involved.

Dr. Basco is Professor, Department of Pediatrics, Medical University of South Carolina (MUSC); Director, Division of General Pediatrics, Department of Pediatrics, MUSC Children’s Hospital, Charleston, South Carolina. He has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Many infants have experienced an episode of apnea, defined as a pause in respiration of 20 seconds or more. Most episodes remain unexplained, and no underlying cause can be found. Historically, these were referred to as “near-miss SIDS,” episodes, but that label suggested that all of these events would have ended in death had someone not intervened. New descriptive terminology was needed.

In the mid-1980s, the term “apparent life-threatening event” (ALTE) was adopted. But that term, too, was an overstatement, because although scary for parents, these brief apnea episodes were not, in most cases, truly life-threatening.

In 2013, authors of a systematic review coined the term “brief resolved unexplained event” (BRUE). This review also addressed the history and physical exam features associated with risk for a subsequent episode. It was felt that hospitalization and testing might be warranted if certain infants could be identified as high risk for recurrence.

What Is Considered a BRUE?

In the current working definition of BRUE, the child must be < 1 year old. The episode must be a sudden, brief, and resolved, with one or more of these characteristics:

• Cyanosis or pallor (but not turning red)
• A change in breathing (absent, decreased, or irregular)
• A change in tone (hypertonia or hypotonia)
• A change in responsiveness.

Furthermore, to qualify as a BRUE, no explanation can be found for the event based on the history and physical examination but before any laboratory testing is done. The definition also excludes children with known potential explanatory diagnoses (such as gastroesophageal reflux or bronchiolitis) and those who are otherwise symptomatically ill at the time of the event.
 

Decision to Admit and Recurrence Risk

An apnea event in an otherwise healthy infant, regardless of what it’s called, puts providers and parents in a difficult position. Should the infant be hospitalized for further monitoring and potentially more invasive testing to determine the cause of the episode? And what are the chances that the episode will be repeated?

A clinical practice guideline (CPG) for BRUE, widely adopted in 2016, resulted in significant reductions in healthcare utilization. The CPG attempted to identify low-risk infants who could safely be discharged from the emergency department. Although the CPG improved outcomes, experts acknowledged that an underlying problem was not likely to be identified even among infants deemed high risk, and these infants would be hospitalized unnecessarily.

Available data were simply insufficient to support this decision. So, with the goal of identifying factors that could help predict recurrent BRUE risk, a 15-hospital collaborative study was undertaken, followed by the development and validation of a clinical decision rule for predicting the risk for a serious underlying diagnosis or event recurrence among infants presenting with BRUE.

Here’s what we learned from more than 3000 cases of BRUE.

First, it turns out that it’s not easy to determine whether an infant is at low or high risk for recurrence of BRUE. Initially, 91.5% of patients enrolled in the study would have been labeled high risk.

Furthermore, a BRUE recurred in 14.3% of the cohort, and 4.8% of high-risk infants were found to have a serious undiagnosed condition. Seizures, airway anomalies, and gastroesophageal reflux were the top three causes of BRUE, but the spectrum of underlying pathology was quite considerable.

The problem was that 4.6% of the entire cohort were found to have a serious underlying condition, nearly identical to the proportion of high-risk infants with these conditions. This prompted the question of whether simply labeling infants “high risk” was really appropriate any longer. 
 

Revised BRUE Management

Although it hasn’t been possible to group infants neatly in low and high-risk categories, the data from that large cohort led to the development of the BRUE 2.0 criteria, which enabled more focused risk assessment of an infant who experienced a BRUE. With an app on MDCalc, these criteria allow providers to ascertain, and show families, a visual representation of their infant’s individualized risk for a subsequent BRUE and of having a serious underlying condition.

The cohort study also identified red flags from the history or physical exam of infants who experienced a BRUE: weight loss, failure to thrive, or a history of feeding problems. Exam findings such as a bulging fontanelle, forceful or bilious emesis, and evidence of gastrointestinal (GI) bleeding suggest a medical diagnosis rather than a BRUE. If GI-related causes are high on the differential, a feeding evaluation can be helpful. A feeding evaluation can be done in the outpatient setting and does not require hospitalization.

For suspicion of an underlying neurological condition (such as seizures), experts recommend obtaining a short EEG, which is highly sensitive for detecting infantile spasms and encephalopathy. They recommend reserving MRI for infants with abnormalities on EEG or physical exam. Metabolic or genetic testing should be done only if the infant looks ill, because most patients with genetic or inborn errors of metabolism will continue to have symptoms as they become older.

The approach to BRUE has moved into the realm of shared decision-making with families. The likelihood of identifying a serious diagnosis is low for most of these children. And unfortunately, no single test can diagnose the full spectrum of potential explanatory diagnoses. For example, data from 2023 demonstrate that only 1.1% of lab tests following a BRUE contributed to a diagnosis, and most of the time that was a positive viral test. Similarly, imaging was helpful in only 1.5% of cases. So, explaining the evidence and deciding along with parents what is reasonable to do (or not do) is the current state of affairs.
 

My Take

As I reflect back on two and a half decades of caring for these patients, I believe that recent data have helped us a great deal. We do less testing and admit fewer infants to the hospital than we did 20 years ago, and that’s a good thing. Nevertheless, looking for a few red flags, having a high index of suspicion when the clinical exam is abnormal, and engaging in shared decision-making with families can help make the caring for these challenging patients more bearable and lead to better outcomes for all involved.

Dr. Basco is Professor, Department of Pediatrics, Medical University of South Carolina (MUSC); Director, Division of General Pediatrics, Department of Pediatrics, MUSC Children’s Hospital, Charleston, South Carolina. He has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Many infants have experienced an episode of apnea, defined as a pause in respiration of 20 seconds or more. Most episodes remain unexplained, and no underlying cause can be found. Historically, these were referred to as “near-miss SIDS,” episodes, but that label suggested that all of these events would have ended in death had someone not intervened. New descriptive terminology was needed.

In the mid-1980s, the term “apparent life-threatening event” (ALTE) was adopted. But that term, too, was an overstatement, because although scary for parents, these brief apnea episodes were not, in most cases, truly life-threatening.

In 2013, authors of a systematic review coined the term “brief resolved unexplained event” (BRUE). This review also addressed the history and physical exam features associated with risk for a subsequent episode. It was felt that hospitalization and testing might be warranted if certain infants could be identified as high risk for recurrence.

What Is Considered a BRUE?

In the current working definition of BRUE, the child must be < 1 year old. The episode must be a sudden, brief, and resolved, with one or more of these characteristics:

• Cyanosis or pallor (but not turning red)
• A change in breathing (absent, decreased, or irregular)
• A change in tone (hypertonia or hypotonia)
• A change in responsiveness.

Furthermore, to qualify as a BRUE, no explanation can be found for the event based on the history and physical examination but before any laboratory testing is done. The definition also excludes children with known potential explanatory diagnoses (such as gastroesophageal reflux or bronchiolitis) and those who are otherwise symptomatically ill at the time of the event.
 

Decision to Admit and Recurrence Risk

An apnea event in an otherwise healthy infant, regardless of what it’s called, puts providers and parents in a difficult position. Should the infant be hospitalized for further monitoring and potentially more invasive testing to determine the cause of the episode? And what are the chances that the episode will be repeated?

A clinical practice guideline (CPG) for BRUE, widely adopted in 2016, resulted in significant reductions in healthcare utilization. The CPG attempted to identify low-risk infants who could safely be discharged from the emergency department. Although the CPG improved outcomes, experts acknowledged that an underlying problem was not likely to be identified even among infants deemed high risk, and these infants would be hospitalized unnecessarily.

Available data were simply insufficient to support this decision. So, with the goal of identifying factors that could help predict recurrent BRUE risk, a 15-hospital collaborative study was undertaken, followed by the development and validation of a clinical decision rule for predicting the risk for a serious underlying diagnosis or event recurrence among infants presenting with BRUE.

Here’s what we learned from more than 3000 cases of BRUE.

First, it turns out that it’s not easy to determine whether an infant is at low or high risk for recurrence of BRUE. Initially, 91.5% of patients enrolled in the study would have been labeled high risk.

Furthermore, a BRUE recurred in 14.3% of the cohort, and 4.8% of high-risk infants were found to have a serious undiagnosed condition. Seizures, airway anomalies, and gastroesophageal reflux were the top three causes of BRUE, but the spectrum of underlying pathology was quite considerable.

The problem was that 4.6% of the entire cohort were found to have a serious underlying condition, nearly identical to the proportion of high-risk infants with these conditions. This prompted the question of whether simply labeling infants “high risk” was really appropriate any longer. 
 

Revised BRUE Management

Although it hasn’t been possible to group infants neatly in low and high-risk categories, the data from that large cohort led to the development of the BRUE 2.0 criteria, which enabled more focused risk assessment of an infant who experienced a BRUE. With an app on MDCalc, these criteria allow providers to ascertain, and show families, a visual representation of their infant’s individualized risk for a subsequent BRUE and of having a serious underlying condition.

The cohort study also identified red flags from the history or physical exam of infants who experienced a BRUE: weight loss, failure to thrive, or a history of feeding problems. Exam findings such as a bulging fontanelle, forceful or bilious emesis, and evidence of gastrointestinal (GI) bleeding suggest a medical diagnosis rather than a BRUE. If GI-related causes are high on the differential, a feeding evaluation can be helpful. A feeding evaluation can be done in the outpatient setting and does not require hospitalization.

For suspicion of an underlying neurological condition (such as seizures), experts recommend obtaining a short EEG, which is highly sensitive for detecting infantile spasms and encephalopathy. They recommend reserving MRI for infants with abnormalities on EEG or physical exam. Metabolic or genetic testing should be done only if the infant looks ill, because most patients with genetic or inborn errors of metabolism will continue to have symptoms as they become older.

The approach to BRUE has moved into the realm of shared decision-making with families. The likelihood of identifying a serious diagnosis is low for most of these children. And unfortunately, no single test can diagnose the full spectrum of potential explanatory diagnoses. For example, data from 2023 demonstrate that only 1.1% of lab tests following a BRUE contributed to a diagnosis, and most of the time that was a positive viral test. Similarly, imaging was helpful in only 1.5% of cases. So, explaining the evidence and deciding along with parents what is reasonable to do (or not do) is the current state of affairs.
 

My Take

As I reflect back on two and a half decades of caring for these patients, I believe that recent data have helped us a great deal. We do less testing and admit fewer infants to the hospital than we did 20 years ago, and that’s a good thing. Nevertheless, looking for a few red flags, having a high index of suspicion when the clinical exam is abnormal, and engaging in shared decision-making with families can help make the caring for these challenging patients more bearable and lead to better outcomes for all involved.

Dr. Basco is Professor, Department of Pediatrics, Medical University of South Carolina (MUSC); Director, Division of General Pediatrics, Department of Pediatrics, MUSC Children’s Hospital, Charleston, South Carolina. He has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

In my mind’s calendar, two dates stand out. Both far enough away that I don’t have to think about them too much right now, but near enough that they can’t be forgotten about, either.

On September 30, 2028, my office lease ends, and in 2029 my neurology board certification has to be renewed. I’ll be in my early 60s then and I’ve been a practicing neurologist for 30 years.

I have no idea what I’m going to do. Of course, a lot can happen between now and then, and a lot of variables come into the calculus of when to retire.

After all these years, I still enjoy my job. It gives me the purpose that I wanted so long ago when I applied to medical school. The late William Pancoe, associate dean when I was at Creighton, always told us to remember how we felt when we got that acceptance letter — we’d need it to keep us going through medical school.

And, even now, I still remember the call from my dad that it had arrived. What a moment that was. I have no regrets. I can’t imagine doing anything else.

But in 4 years how much longer will I want to practice? Hopefully I’ll be faced with that decision. Will I want to renew the lease for 2 years? 5 years? I like my little office. It’s far from gleaming, there’s no TV or Keurig in the lobby, the carpet, paint, and furnishings are still from the early 90s when the place was built. But it’s my home away from home. I spend anywhere from 40-60 hours/week there. It’s quiet and (at least for me) cozy. Would I want to give that up and move to a smaller, shared place, for the remainder of my career? Or just close down?

Likewise, will I want to renew my board certification? Granted, that isn’t necessary to practice, but it certainly looks better to have it. To do that I’ll have to fork over a decent chunk of change to take the test, more money for a review course, and spend some time studying. Strange to think that at 63 I might be back at my desk (same desk, by the way) studying for a test like I did in college and medical school. But, if I want to keep playing doctor, that’s what I’ll have to do.

Four years to think about this. The same amount of time I spent each in high school, medical school, and residency. For that matter, the same amount of time since we all went into quarantine.

Doesn’t seem that long, does it?

I guess I’ve got some thinking to do.
 

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

In my mind’s calendar, two dates stand out. Both far enough away that I don’t have to think about them too much right now, but near enough that they can’t be forgotten about, either.

On September 30, 2028, my office lease ends, and in 2029 my neurology board certification has to be renewed. I’ll be in my early 60s then and I’ve been a practicing neurologist for 30 years.

I have no idea what I’m going to do. Of course, a lot can happen between now and then, and a lot of variables come into the calculus of when to retire.

After all these years, I still enjoy my job. It gives me the purpose that I wanted so long ago when I applied to medical school. The late William Pancoe, associate dean when I was at Creighton, always told us to remember how we felt when we got that acceptance letter — we’d need it to keep us going through medical school.

And, even now, I still remember the call from my dad that it had arrived. What a moment that was. I have no regrets. I can’t imagine doing anything else.

But in 4 years how much longer will I want to practice? Hopefully I’ll be faced with that decision. Will I want to renew the lease for 2 years? 5 years? I like my little office. It’s far from gleaming, there’s no TV or Keurig in the lobby, the carpet, paint, and furnishings are still from the early 90s when the place was built. But it’s my home away from home. I spend anywhere from 40-60 hours/week there. It’s quiet and (at least for me) cozy. Would I want to give that up and move to a smaller, shared place, for the remainder of my career? Or just close down?

Likewise, will I want to renew my board certification? Granted, that isn’t necessary to practice, but it certainly looks better to have it. To do that I’ll have to fork over a decent chunk of change to take the test, more money for a review course, and spend some time studying. Strange to think that at 63 I might be back at my desk (same desk, by the way) studying for a test like I did in college and medical school. But, if I want to keep playing doctor, that’s what I’ll have to do.

Four years to think about this. The same amount of time I spent each in high school, medical school, and residency. For that matter, the same amount of time since we all went into quarantine.

Doesn’t seem that long, does it?

I guess I’ve got some thinking to do.
 

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

In my mind’s calendar, two dates stand out. Both far enough away that I don’t have to think about them too much right now, but near enough that they can’t be forgotten about, either.

On September 30, 2028, my office lease ends, and in 2029 my neurology board certification has to be renewed. I’ll be in my early 60s then and I’ve been a practicing neurologist for 30 years.

I have no idea what I’m going to do. Of course, a lot can happen between now and then, and a lot of variables come into the calculus of when to retire.

After all these years, I still enjoy my job. It gives me the purpose that I wanted so long ago when I applied to medical school. The late William Pancoe, associate dean when I was at Creighton, always told us to remember how we felt when we got that acceptance letter — we’d need it to keep us going through medical school.

And, even now, I still remember the call from my dad that it had arrived. What a moment that was. I have no regrets. I can’t imagine doing anything else.

But in 4 years how much longer will I want to practice? Hopefully I’ll be faced with that decision. Will I want to renew the lease for 2 years? 5 years? I like my little office. It’s far from gleaming, there’s no TV or Keurig in the lobby, the carpet, paint, and furnishings are still from the early 90s when the place was built. But it’s my home away from home. I spend anywhere from 40-60 hours/week there. It’s quiet and (at least for me) cozy. Would I want to give that up and move to a smaller, shared place, for the remainder of my career? Or just close down?

Likewise, will I want to renew my board certification? Granted, that isn’t necessary to practice, but it certainly looks better to have it. To do that I’ll have to fork over a decent chunk of change to take the test, more money for a review course, and spend some time studying. Strange to think that at 63 I might be back at my desk (same desk, by the way) studying for a test like I did in college and medical school. But, if I want to keep playing doctor, that’s what I’ll have to do.

Four years to think about this. The same amount of time I spent each in high school, medical school, and residency. For that matter, the same amount of time since we all went into quarantine.

Doesn’t seem that long, does it?

I guess I’ve got some thinking to do.
 

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

Has COVID replaced syphilis as the great imitator? At the turn of the 20th century, Sir William Osler was quoted as saying, “He who knows syphilis knows medicine.”

If you have any doubts about the “imitator” analogy, simply use any broad search engine or AI portal and enter “what is the differential diagnosis of primary syphilis, or secondary syphilis, or tertiary syphilis?” A plethora of diseases across many body systems appears.
 

Another Great Pretender?

Did you or do you now have long COVID? How do you know? Do you even know what long COVID is? How would you diagnosis it?

When asked about long COVID, this is what large language model source bard.google.com had to say:

Long COVID, also known as post-COVID conditions or PASC, is a complex condition that can occur in people who have had COVID-19, even if their initial illness was mild or even asymptomatic. It’s characterized by a wide range of symptoms that can last for weeks, months, or even years after the initial infection.

Symptoms of long COVID can include: fatigue, shortness of breath, brain fog (trouble thinking or concentrating), loss of smell or taste, sleep problems, muscle pain, joint pain, headache, dizziness, depression or anxiety, heart palpitations, gastrointestinal problems.

Duh!!! It reads much like a continuation of the symptoms of acute COVID. Bard continued:

The exact cause of long COVID is still unknown, but there are several theories. One possibility is that the virus itself can damage organs and tissues, leading to ongoing symptoms. Another possibility is that the immune system’s response to the virus can continue to cause inflammation even after the virus is gone.

Human intelligence source Wikipedia says this:

Long COVID or long-haul COVID is a group of health problems persisting or developing after an initial COVID-19 infection. Symptoms can last weeks, months or years and are often debilitating. The World Health Organization defines long COVID as starting three months after infection, but other definitions put the start of long COVID at four weeks.

Highly varied, including post-exertional malaise (symptoms made worse with effort), fatigue, muscle pain, shortness of breath, chest pain, and cognitive dysfunction (brain fog).
 

Acute COVID to Long COVID

The World Health Organization estimates that 36 million people in the European region have developed long COVID in the first 3 years of the pandemic. That›s a lot.

We all know that the common signs and symptoms of acute COVID-19 include fever or chills, a dry cough and shortness of breath, feeling very tired, muscle or body aches, headache, loss of taste or smell, sore throat, congestion, runny nose, nausea, vomiting, and diarrhea. Except for the taste and smell findings, every one of these symptoms or signs could indicate a different virus infection or even some type of allergy. My point is the nonspecificity in this list.

Uncommon signs and symptoms of acute COVID include a flat skin rash covered with small bumps, discolored swollen areas on the fingers and toes (COVID toes), and hives. The skin of hands, wrists, or ankles also can be affected. Blisters, itchiness, rough skin, or pus can be seen.

Severe confusion (delirium) might be the main or only symptom of COVID-19 in older people. This COVID-19 symptom is linked with a high risk for poor outcomes, including death. Pink eye (conjunctivitis) can be a COVID-19 symptom. Other eye problems linked to COVID-19 are light sensitivity, sore eyes, and itchy eyes. Acute myocarditis, tinnitus, vertigo, and hearing loss have been reported. And 1-4 weeks after the onset of COVID-19 infection, a patient may experience de novo reactive synovitis and arthritis of any joints.

So, take your pick. Myriad symptoms, signs, diseases, diagnoses, and organ systems — still present, recurring, just appearing, apparently de novo, or after asymptomatic infection. We have so much still to learn.

What big-time symptoms, signs, and major diseases are not on any of these lists? Obviously, cancer, atherosclerotic cardiovascular diseases, obesity, bone diseases, and competitive infections. But be patient; the lingering effects of direct tissue invasion by the virus as well as a wide range of immunologic reactions may just be getting started. Mitochondrial damage, especially in muscles, is increasingly a pathophysiologic suspect.

Human diseases can be physical or mental; and in COVID, that twain not only meet but mix and mingle freely, and may even merge into psychosoma. Don’t ever forget that. Consider “fatigue.” Who among us, COVID or NOVID, does not experience that from time to time?

Or consider brain fog as a common reported symptom of COVID. What on earth is that actually? How can a person know they have brain fog, or whether they had it and are over it?

We need one or more lab or other diagnostic tests that can objectively confirm the diagnosis of long COVID.
 

Useful Progress?

A recent research paper in Science reported intriguing chemical findings that seemed to point a finger at some form of complement dysregulation as a potential disease marker for long COVID. Unfortunately, some critics have pointed out that this entire study may be invalid or irrelevant because the New York cohort was recruited in 2020, before vaccines were available. The Zurich cohort was recruited up until April 2021, so some may have been vaccinated.

Then this news organization came along in early January 2024 with an article about COVID causing not only more than a million American deaths but also more than 5000 deaths from long COVID. We physicians don’t really know what long COVID even is, but we have to sign death certificates blaming thousands of deaths on it anyway? And rolling back the clock to 2020: Are patients dying from COVID or with COVID, according to death certificates?Now, armed with the knowledge that “documented serious post–COVID-19 conditions include cardiovascular, pulmonary, neurological, renal, endocrine, hematological, and gastrointestinal complications, as well as death,” CDC has published clear and fairly concise instructions on how to address post-acute COVID sequelae on death certificates.

In late January, this news organization painted a hopeful picture by naming four phenotypes of long COVID, suggesting that such divisions might further our understanding, including prognosis, and even therapy for this condition. Among the clinical phenotypes of (1) chronic fatigue–like syndrome, headache, and memory loss; (2) respiratory syndrome (which includes cough and difficulty breathing); (3) chronic pain; and (4) neurosensorial syndrome (which causes an altered sense of taste and smell), overlap is clearly possible but isn›t addressed.

I see these recent developments as needed and useful progress, but we are still left with…not much. So, when you tell me that you do or do not have long COVID, I will say to you, “How do you know?”

I also say: She/he/they who know COVID know medicine.

A version of this article first appeared on Medscape.com.

Has COVID replaced syphilis as the great imitator? At the turn of the 20th century, Sir William Osler was quoted as saying, “He who knows syphilis knows medicine.”

If you have any doubts about the “imitator” analogy, simply use any broad search engine or AI portal and enter “what is the differential diagnosis of primary syphilis, or secondary syphilis, or tertiary syphilis?” A plethora of diseases across many body systems appears.
 

Another Great Pretender?

Did you or do you now have long COVID? How do you know? Do you even know what long COVID is? How would you diagnosis it?

When asked about long COVID, this is what large language model source bard.google.com had to say:

Long COVID, also known as post-COVID conditions or PASC, is a complex condition that can occur in people who have had COVID-19, even if their initial illness was mild or even asymptomatic. It’s characterized by a wide range of symptoms that can last for weeks, months, or even years after the initial infection.

Symptoms of long COVID can include: fatigue, shortness of breath, brain fog (trouble thinking or concentrating), loss of smell or taste, sleep problems, muscle pain, joint pain, headache, dizziness, depression or anxiety, heart palpitations, gastrointestinal problems.

Duh!!! It reads much like a continuation of the symptoms of acute COVID. Bard continued:

The exact cause of long COVID is still unknown, but there are several theories. One possibility is that the virus itself can damage organs and tissues, leading to ongoing symptoms. Another possibility is that the immune system’s response to the virus can continue to cause inflammation even after the virus is gone.

Human intelligence source Wikipedia says this:

Long COVID or long-haul COVID is a group of health problems persisting or developing after an initial COVID-19 infection. Symptoms can last weeks, months or years and are often debilitating. The World Health Organization defines long COVID as starting three months after infection, but other definitions put the start of long COVID at four weeks.

Highly varied, including post-exertional malaise (symptoms made worse with effort), fatigue, muscle pain, shortness of breath, chest pain, and cognitive dysfunction (brain fog).
 

Acute COVID to Long COVID

The World Health Organization estimates that 36 million people in the European region have developed long COVID in the first 3 years of the pandemic. That›s a lot.

We all know that the common signs and symptoms of acute COVID-19 include fever or chills, a dry cough and shortness of breath, feeling very tired, muscle or body aches, headache, loss of taste or smell, sore throat, congestion, runny nose, nausea, vomiting, and diarrhea. Except for the taste and smell findings, every one of these symptoms or signs could indicate a different virus infection or even some type of allergy. My point is the nonspecificity in this list.

Uncommon signs and symptoms of acute COVID include a flat skin rash covered with small bumps, discolored swollen areas on the fingers and toes (COVID toes), and hives. The skin of hands, wrists, or ankles also can be affected. Blisters, itchiness, rough skin, or pus can be seen.

Severe confusion (delirium) might be the main or only symptom of COVID-19 in older people. This COVID-19 symptom is linked with a high risk for poor outcomes, including death. Pink eye (conjunctivitis) can be a COVID-19 symptom. Other eye problems linked to COVID-19 are light sensitivity, sore eyes, and itchy eyes. Acute myocarditis, tinnitus, vertigo, and hearing loss have been reported. And 1-4 weeks after the onset of COVID-19 infection, a patient may experience de novo reactive synovitis and arthritis of any joints.

So, take your pick. Myriad symptoms, signs, diseases, diagnoses, and organ systems — still present, recurring, just appearing, apparently de novo, or after asymptomatic infection. We have so much still to learn.

What big-time symptoms, signs, and major diseases are not on any of these lists? Obviously, cancer, atherosclerotic cardiovascular diseases, obesity, bone diseases, and competitive infections. But be patient; the lingering effects of direct tissue invasion by the virus as well as a wide range of immunologic reactions may just be getting started. Mitochondrial damage, especially in muscles, is increasingly a pathophysiologic suspect.

Human diseases can be physical or mental; and in COVID, that twain not only meet but mix and mingle freely, and may even merge into psychosoma. Don’t ever forget that. Consider “fatigue.” Who among us, COVID or NOVID, does not experience that from time to time?

Or consider brain fog as a common reported symptom of COVID. What on earth is that actually? How can a person know they have brain fog, or whether they had it and are over it?

We need one or more lab or other diagnostic tests that can objectively confirm the diagnosis of long COVID.
 

Useful Progress?

A recent research paper in Science reported intriguing chemical findings that seemed to point a finger at some form of complement dysregulation as a potential disease marker for long COVID. Unfortunately, some critics have pointed out that this entire study may be invalid or irrelevant because the New York cohort was recruited in 2020, before vaccines were available. The Zurich cohort was recruited up until April 2021, so some may have been vaccinated.

Then this news organization came along in early January 2024 with an article about COVID causing not only more than a million American deaths but also more than 5000 deaths from long COVID. We physicians don’t really know what long COVID even is, but we have to sign death certificates blaming thousands of deaths on it anyway? And rolling back the clock to 2020: Are patients dying from COVID or with COVID, according to death certificates?Now, armed with the knowledge that “documented serious post–COVID-19 conditions include cardiovascular, pulmonary, neurological, renal, endocrine, hematological, and gastrointestinal complications, as well as death,” CDC has published clear and fairly concise instructions on how to address post-acute COVID sequelae on death certificates.

In late January, this news organization painted a hopeful picture by naming four phenotypes of long COVID, suggesting that such divisions might further our understanding, including prognosis, and even therapy for this condition. Among the clinical phenotypes of (1) chronic fatigue–like syndrome, headache, and memory loss; (2) respiratory syndrome (which includes cough and difficulty breathing); (3) chronic pain; and (4) neurosensorial syndrome (which causes an altered sense of taste and smell), overlap is clearly possible but isn›t addressed.

I see these recent developments as needed and useful progress, but we are still left with…not much. So, when you tell me that you do or do not have long COVID, I will say to you, “How do you know?”

I also say: She/he/they who know COVID know medicine.

A version of this article first appeared on Medscape.com.

Has COVID replaced syphilis as the great imitator? At the turn of the 20th century, Sir William Osler was quoted as saying, “He who knows syphilis knows medicine.”

If you have any doubts about the “imitator” analogy, simply use any broad search engine or AI portal and enter “what is the differential diagnosis of primary syphilis, or secondary syphilis, or tertiary syphilis?” A plethora of diseases across many body systems appears.
 

Another Great Pretender?

Did you or do you now have long COVID? How do you know? Do you even know what long COVID is? How would you diagnosis it?

When asked about long COVID, this is what large language model source bard.google.com had to say:

Long COVID, also known as post-COVID conditions or PASC, is a complex condition that can occur in people who have had COVID-19, even if their initial illness was mild or even asymptomatic. It’s characterized by a wide range of symptoms that can last for weeks, months, or even years after the initial infection.

Symptoms of long COVID can include: fatigue, shortness of breath, brain fog (trouble thinking or concentrating), loss of smell or taste, sleep problems, muscle pain, joint pain, headache, dizziness, depression or anxiety, heart palpitations, gastrointestinal problems.

Duh!!! It reads much like a continuation of the symptoms of acute COVID. Bard continued:

The exact cause of long COVID is still unknown, but there are several theories. One possibility is that the virus itself can damage organs and tissues, leading to ongoing symptoms. Another possibility is that the immune system’s response to the virus can continue to cause inflammation even after the virus is gone.

Human intelligence source Wikipedia says this:

Long COVID or long-haul COVID is a group of health problems persisting or developing after an initial COVID-19 infection. Symptoms can last weeks, months or years and are often debilitating. The World Health Organization defines long COVID as starting three months after infection, but other definitions put the start of long COVID at four weeks.

Highly varied, including post-exertional malaise (symptoms made worse with effort), fatigue, muscle pain, shortness of breath, chest pain, and cognitive dysfunction (brain fog).
 

Acute COVID to Long COVID

The World Health Organization estimates that 36 million people in the European region have developed long COVID in the first 3 years of the pandemic. That›s a lot.

We all know that the common signs and symptoms of acute COVID-19 include fever or chills, a dry cough and shortness of breath, feeling very tired, muscle or body aches, headache, loss of taste or smell, sore throat, congestion, runny nose, nausea, vomiting, and diarrhea. Except for the taste and smell findings, every one of these symptoms or signs could indicate a different virus infection or even some type of allergy. My point is the nonspecificity in this list.

Uncommon signs and symptoms of acute COVID include a flat skin rash covered with small bumps, discolored swollen areas on the fingers and toes (COVID toes), and hives. The skin of hands, wrists, or ankles also can be affected. Blisters, itchiness, rough skin, or pus can be seen.

Severe confusion (delirium) might be the main or only symptom of COVID-19 in older people. This COVID-19 symptom is linked with a high risk for poor outcomes, including death. Pink eye (conjunctivitis) can be a COVID-19 symptom. Other eye problems linked to COVID-19 are light sensitivity, sore eyes, and itchy eyes. Acute myocarditis, tinnitus, vertigo, and hearing loss have been reported. And 1-4 weeks after the onset of COVID-19 infection, a patient may experience de novo reactive synovitis and arthritis of any joints.

So, take your pick. Myriad symptoms, signs, diseases, diagnoses, and organ systems — still present, recurring, just appearing, apparently de novo, or after asymptomatic infection. We have so much still to learn.

What big-time symptoms, signs, and major diseases are not on any of these lists? Obviously, cancer, atherosclerotic cardiovascular diseases, obesity, bone diseases, and competitive infections. But be patient; the lingering effects of direct tissue invasion by the virus as well as a wide range of immunologic reactions may just be getting started. Mitochondrial damage, especially in muscles, is increasingly a pathophysiologic suspect.

Human diseases can be physical or mental; and in COVID, that twain not only meet but mix and mingle freely, and may even merge into psychosoma. Don’t ever forget that. Consider “fatigue.” Who among us, COVID or NOVID, does not experience that from time to time?

Or consider brain fog as a common reported symptom of COVID. What on earth is that actually? How can a person know they have brain fog, or whether they had it and are over it?

We need one or more lab or other diagnostic tests that can objectively confirm the diagnosis of long COVID.
 

Useful Progress?

A recent research paper in Science reported intriguing chemical findings that seemed to point a finger at some form of complement dysregulation as a potential disease marker for long COVID. Unfortunately, some critics have pointed out that this entire study may be invalid or irrelevant because the New York cohort was recruited in 2020, before vaccines were available. The Zurich cohort was recruited up until April 2021, so some may have been vaccinated.

Then this news organization came along in early January 2024 with an article about COVID causing not only more than a million American deaths but also more than 5000 deaths from long COVID. We physicians don’t really know what long COVID even is, but we have to sign death certificates blaming thousands of deaths on it anyway? And rolling back the clock to 2020: Are patients dying from COVID or with COVID, according to death certificates?Now, armed with the knowledge that “documented serious post–COVID-19 conditions include cardiovascular, pulmonary, neurological, renal, endocrine, hematological, and gastrointestinal complications, as well as death,” CDC has published clear and fairly concise instructions on how to address post-acute COVID sequelae on death certificates.

In late January, this news organization painted a hopeful picture by naming four phenotypes of long COVID, suggesting that such divisions might further our understanding, including prognosis, and even therapy for this condition. Among the clinical phenotypes of (1) chronic fatigue–like syndrome, headache, and memory loss; (2) respiratory syndrome (which includes cough and difficulty breathing); (3) chronic pain; and (4) neurosensorial syndrome (which causes an altered sense of taste and smell), overlap is clearly possible but isn›t addressed.

I see these recent developments as needed and useful progress, but we are still left with…not much. So, when you tell me that you do or do not have long COVID, I will say to you, “How do you know?”

I also say: She/he/they who know COVID know medicine.

A version of this article first appeared on Medscape.com.