MDedge Dermatology

The Food and Drug Administration has approved injectable poly-L-lactic acid (PLLA-SCA) for the correction of fine lines and wrinkles in the cheek, the manufacturer announced on April 26.

The treatment, marketed as Sculptra, is the first FDA-approved PLLA collagen stimulator that, “when injected into the cheek area, helps stimulate natural collagen production to smooth wrinkles and improve skin quality such as firmness and glow,” according to a press release from the manufacturer, Galderma. Sculptra was first approved for aesthetic use in 2009 in the United States and is now available in more than 40 countries.

Olivier Le Moal/Getty Images

With this expanded approval, PLLA-SCA is now indicated for use in people with healthy immune systems for correcting shallow to deep nasolabial fold contour deficiencies, fine lines, and wrinkles in the cheeks and other facial areas.
 

94% have enduring improvement at 2 years

In a clinical trial, PLLA-SCA achieved the primary efficacy endpoint of at least a 1-grade improvement in wrinkles on both cheeks concurrently at rest and its secondary endpoint of improving cheek wrinkles when smiling for up to 2 years, the company states.

According to Galderma, patients showed aesthetic improvement in cheek wrinkles throughout the study; 96% showed improvement at 3 months, 94% showed improvement at 1 year, and 94% showed improvement at 2 years.

The most common side effects after initial treatment are injection site swelling, tenderness, redness, pain, bruising, bleeding, itching, and lumps, according to the company. Other side effects may include small lumps under the skin that are sometimes noticeable when pressing on the treated area. 

PLLA-SCA is available only through a licensed practitioner and should not be used by people allergic to any ingredient of the product or who have a history of keloid formation or hypertrophic scarring. The company notes that safety has not been established in patients who are pregnant, lactating, breastfeeding, or younger than 18.

In its instruction to clinicians, the company warns the treatment should not be injected into the blood vessels “as it may cause vascular occlusion, infarction, or embolic phenomena.”

Skin sores, cysts, pimples, rashes, hives, or infection should be healed completely before injecting the treatment, the company cautions. PLLA-SCA should not be injected into the red area of the lip or in the periorbital area.

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

The Food and Drug Administration has approved injectable poly-L-lactic acid (PLLA-SCA) for the correction of fine lines and wrinkles in the cheek, the manufacturer announced on April 26.

The treatment, marketed as Sculptra, is the first FDA-approved PLLA collagen stimulator that, “when injected into the cheek area, helps stimulate natural collagen production to smooth wrinkles and improve skin quality such as firmness and glow,” according to a press release from the manufacturer, Galderma. Sculptra was first approved for aesthetic use in 2009 in the United States and is now available in more than 40 countries.

Olivier Le Moal/Getty Images

With this expanded approval, PLLA-SCA is now indicated for use in people with healthy immune systems for correcting shallow to deep nasolabial fold contour deficiencies, fine lines, and wrinkles in the cheeks and other facial areas.
 

94% have enduring improvement at 2 years

In a clinical trial, PLLA-SCA achieved the primary efficacy endpoint of at least a 1-grade improvement in wrinkles on both cheeks concurrently at rest and its secondary endpoint of improving cheek wrinkles when smiling for up to 2 years, the company states.

According to Galderma, patients showed aesthetic improvement in cheek wrinkles throughout the study; 96% showed improvement at 3 months, 94% showed improvement at 1 year, and 94% showed improvement at 2 years.

The most common side effects after initial treatment are injection site swelling, tenderness, redness, pain, bruising, bleeding, itching, and lumps, according to the company. Other side effects may include small lumps under the skin that are sometimes noticeable when pressing on the treated area. 

PLLA-SCA is available only through a licensed practitioner and should not be used by people allergic to any ingredient of the product or who have a history of keloid formation or hypertrophic scarring. The company notes that safety has not been established in patients who are pregnant, lactating, breastfeeding, or younger than 18.

In its instruction to clinicians, the company warns the treatment should not be injected into the blood vessels “as it may cause vascular occlusion, infarction, or embolic phenomena.”

Skin sores, cysts, pimples, rashes, hives, or infection should be healed completely before injecting the treatment, the company cautions. PLLA-SCA should not be injected into the red area of the lip or in the periorbital area.

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

The Food and Drug Administration has approved injectable poly-L-lactic acid (PLLA-SCA) for the correction of fine lines and wrinkles in the cheek, the manufacturer announced on April 26.

The treatment, marketed as Sculptra, is the first FDA-approved PLLA collagen stimulator that, “when injected into the cheek area, helps stimulate natural collagen production to smooth wrinkles and improve skin quality such as firmness and glow,” according to a press release from the manufacturer, Galderma. Sculptra was first approved for aesthetic use in 2009 in the United States and is now available in more than 40 countries.

Olivier Le Moal/Getty Images

With this expanded approval, PLLA-SCA is now indicated for use in people with healthy immune systems for correcting shallow to deep nasolabial fold contour deficiencies, fine lines, and wrinkles in the cheeks and other facial areas.
 

94% have enduring improvement at 2 years

In a clinical trial, PLLA-SCA achieved the primary efficacy endpoint of at least a 1-grade improvement in wrinkles on both cheeks concurrently at rest and its secondary endpoint of improving cheek wrinkles when smiling for up to 2 years, the company states.

According to Galderma, patients showed aesthetic improvement in cheek wrinkles throughout the study; 96% showed improvement at 3 months, 94% showed improvement at 1 year, and 94% showed improvement at 2 years.

The most common side effects after initial treatment are injection site swelling, tenderness, redness, pain, bruising, bleeding, itching, and lumps, according to the company. Other side effects may include small lumps under the skin that are sometimes noticeable when pressing on the treated area. 

PLLA-SCA is available only through a licensed practitioner and should not be used by people allergic to any ingredient of the product or who have a history of keloid formation or hypertrophic scarring. The company notes that safety has not been established in patients who are pregnant, lactating, breastfeeding, or younger than 18.

In its instruction to clinicians, the company warns the treatment should not be injected into the blood vessels “as it may cause vascular occlusion, infarction, or embolic phenomena.”

Skin sores, cysts, pimples, rashes, hives, or infection should be healed completely before injecting the treatment, the company cautions. PLLA-SCA should not be injected into the red area of the lip or in the periorbital area.

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

Erythema ab igne (EAI)(also known as toasted skin syndrome) was first described in the British Journal of Dermatology in the 20th century, ¹ though it was known by physicians long before. Reticular netlike skin changes were seen in association with patients who spent extended time directly next to a heat source. This association led to the name of this condition, which literally means “redness by fire.” Indeed, EAI induced by chronic heat exposure has been described across the world for centuries. For example, in the cold regions of northern China, people used to sleep on beds of hot bricks called kang to stay warm at night. The people of India’s Kashmir district carried pots of hot coals called kangri next to the skin under large woven shawls to stay warm. In the past, Irish women often spent much time by a turf- or peat-burning fire. Chronic heat exposure in these cases can lead not only to EAI but also to aggressive types of cancer, often with a latency of 30 years or more. ²

More recently, the invention of home central heating led to a stark decrease in the number of cases associated with combustion-based heat, with a transition to etiologies such as use of hot water bottles, electric blankets, and electric space heaters. Over time, technological advances led to ever-increasing potential causes for EAI, such as laptops or cell phones, car heaters and heated seats, heated blankets,^3,4 infrared lamps for food, and even medical devices such as ultrasound-based heating products and convective temperature management systems for hospitalized patients. As technology evolves, so do the potential causes of EAI, requiring clinicians to diagnose and deduce the cause through a thorough social and medical history as well as a workup on the present illness with considerations for the anatomical location.^5-7 Herein, we describe the etiology of EAI, diagnosis, and treatment options.

Clinical Characteristics

Erythema ab igne begins as mild, transient, and erythematous macules and patches in a reticular pattern that resolve minutes to hours after removal of the heat source. With weeks to months of continued or repeated application of the heat source, the affected area eventually becomes hyperpigmented where there once was erythema (Figures 1 and 2). Sometimes papules, bullae, telangiectasia, and hyperkeratosis also form. The rash usually is asymptomatic, though pain, pruritus, and dysesthesia have been reported.⁷ Dermoscopy of EAI in the hyperpigmented stage can reveal diffuse superficial dark pigmentation, telangiectasia, and mild whitish scaling.⁸ Although the pathogenesis has remained elusive over the years, lesions do seem to be mostly associated with cumulative exposure to heat rather than length of exposure.⁷

Etiology of EAI

Anatomic Location—The affected site depends on the source of heat (Table). Classic examples of this condition include a patient with EAI presenting on the anterior thighs after working in front of a hot oven or a patient with chronic back pain presenting with lower-back EAI secondary to frequent use of a hot water bottle or heating pad.⁷ With evolving technology over the last few decades, new etiologies have become more common—teenagers are presenting with anterior thigh EAI secondary to frequent laptop use^2-29; patients are holding warm cell phones in their pant pockets, leading to unilateral geometric EAI on the anterior thigh (front pocket) or buttock (back pocket)³⁰; plug-in radiators under computer desks are causing EAI on the lower legs^31-34; and automobile seat heaters have been shown to cause EAI on the posterior legs.^5,35-37 Clinicians should consider anatomic location a critical clue for etiology.

Social History—There are rarer and more highly specific causes of EAI than simple heat exposure that can be parsed from a patient’s social history. Occupational exposure has been documented, such as bakers with exposure to ovens, foundry workers with exposure to heated metals, or fast-food workers with chronic exposure to infrared food lamps.^6,7 There also are cultural practices that can cause EAI. For example, the practice of cupping with moxibustion was shown to create a specific pattern in the shape of the cultural tool used.³⁸ When footbaths with Chinese herbal remedies are performed frequently with high heat, they can lead to EAI on the feet with a linear border at the ankles. There also have been reports of kotatsu (heated tables in Japan) leading to lower-body EAI.^39,40 These cultural practices also are more common in patients with darker skin types, which can lead to hyperpigmentation that is difficult to treat, making early diagnosis important.⁷

Medical History—Case reports have shown EAI caused by patients attempting to use heat-based methods for pain relief of an underlying serious disease such as cancer, bowel pathology (abdominal EAI), spinal disc prolapse (midline back EAI),⁴¹ sickle cell anemia, and renal pathology (posterior upper flank EAI).^6,7,40-49 Patients with hypothyroidism or anorexia have been noted to have generalized EAI sparing the face secondary to repeated and extended hot baths or showers.^50-53 One patient with schizophrenia was shown to have associated thermophilia due to a delusion that led the patient to soak in hot baths for long periods of time, leading to EAI.⁵⁴ Finally, all physicians should be aware of iatrogenic causes of EAI, such as use of warming devices, ultrasound-based warming techniques, and laser therapy for lipolysis. Inquire about the patient’s surgical history or intensive care unit stays as well as alternative medicine or chiropractic visits. Obtaining a history of medical procedures can be enlightening when an etiology is not immediately clear.^7,55,56

Diagnosis

Erythema ab igne is a clinical diagnosis based on recognizable cutaneous findings and a clear history of moderate heat exposure. However, when a clinical diagnosis of EAI is not certain (eg, when unable to obtain a clear history from the patient) or when malignant transformation is suspected, a biopsy can be performed. Pathologically, hematoxylin and eosin staining of EAI classically reveals dilated small vascular channels in the superficial dermis, hence a clinically reticular rash; interface dermatitis clinically manifesting as erythema; and pigment incontinence with melanin-laden macrophages consistent with clinical hyperpigmentation. Finally, for unclear reasons, increased numbers of elastic fibers classically are seen in biopsies of EAI.⁷

 

 

Differential Diagnosis

The differential diagnosis for a reticular patch includes livedo reticularis (Figure 3), which usually manifests as a more generalized rash in patients with chronic disease or coagulopathy such as systemic lupus erythematosus, cryoglobulinemia, or Raynaud phenomenon. When differentiating EAI from livedo reticularis or cutis marmorata, consider that both alternative diagnoses are more vascular appearing and are associated with cold exposure rather than heat exposure. In cases that are less reticular, livedo racemosa can be considered in the differential diagnosis. Finally, poikiloderma of Civatte can be reticular, particularly on dermoscopy, but the distribution on the neck with submental sparing should help to distinguish it from EAI unless a heat source around the neck is identified while taking the patient’s history.⁷

In babies, a reticular generalized rash is most likely to be cutis marmorata (Figure 4), which is a physiologic response to cold exposure that resolves with rewarming of the skin. A more serious condition—cutis marmorata telangiectatica congenita (Figure 5)—usually is present at birth, most frequently involves a single extremity, and notably does not resolve with rewarming. This is an important differential for EAI in children because it can be associated with vascular and neurologic anomalies as well as limb asymmetry. Finally, port-wine stains can sometimes be reticular in appearance and can mimic the early erythematous stages of EAI. However, unlike the erythematous stage of EAI, the port-wine stains will be present at birth.⁷

Emerging in 2020, an important differential diagnosis to consider is a cutaneous manifestation of COVID-19 infection. An erythematous, reticular, chilblainlike or transient livedo reticularis–like rash has been described as a cutaneous manifestation of COVID-19. Although the pathophysiology is still being elucidated, it is suspected that this is caused by a major vaso-occlusive crisis secondary to COVID-19–induced thrombotic vasculopathy. Interestingly, the majority of patients with this COVID-related exanthem also displayed symptoms of COVID-19 (eg, fever, cough) at the time of presentation,^57-60 but there also have been cases in patients who were asymptomatic or mildly symptomatic.⁶⁰

In some cases, EAI is an indication to screen for an underlying disease. For example, uncontrolled pain is an opportunity to improve interventions such as modifying the patient’s pain-control regimen, placing a palliative care pain consultation, or checking if the patient has had age-appropriate screenings for malignancy. New focal pain in a patient with a prior diagnosis of cancer may be a sign of a new metastasis. A thermophilic patient leaves opportunity to assess for underlying medical causes such as thyroid abnormalities or social/psychological issues. Geriatric patients who are diagnosed with EAI may need to be assessed for dementia or home safety issues. Patients with a history of diabetes mellitus can unknowingly develop EAI on the lower extremities, which may signal a need to assess the patient for peripheral neuropathy. Patients with gastroparesis secondary to diabetes also may develop EAI on the abdomen secondary to heating pad use for discomfort. These examples are a reminder to consider possible secondary comorbidities in all diagnoses of EAI.⁷ 

Prognosis

Although the prognosis of EAI is excellent if caught early, failure to diagnose this condition can lead to permanent discoloration of the skin and even malignancy.⁶ A rare sequela includes squamous cell carcinoma, most commonly seen in chronic cases of the lower leg, which is likely related to chronic inflammation of the skin.^61-65 Rare cases of poorly differentiated carcinoma,⁶⁶ cutaneous marginal zone lymphoma,⁶⁷ and Merkel cell carcinoma⁶⁸ have been reported. Patients diagnosed with EAI should receive normal periodic surveillance of the skin based on their medical history, though the physician should have an increased suspicion and plan for biopsy of any nodules or ulcerations found on the skin of the affected area.⁷

Treatments

Once the diagnosis of EAI is made, treatment starts with removal of the heat source causing the rash. Because the rash usually is asymptomatic, further treatment typically is not required. The discoloration can resolve over months or years, but permanent hyperpigmentation is not uncommon. If hyperpigmentation persists despite removal of the heat source and the patient desires further treatment for discoloration, there are few treatment options, none of which are approved by the US Food and Drug Administration for this condition.⁷ There is some evidence for the use of Nd:YAG lasers to reduce hyperpigmentation in EAI.⁶⁹ There have been some reports of treatment using topical hydroquinone and topical tretinoin in an attempt to lighten the skin. If associated hyperkeratosis or other epithelial atypia is present, the use of 5-fluorouracil may show some improvement.⁷⁰ One case report has been published of successful treatment with systemic mesoglycan and topical bioflavonoids.⁷¹ It also is conceivable that medications used to treat postinflammatory hyperpigmentation may be helpful in this condition (eg, kojic acid, arbutin, mild topical steroids, azelaic acid). Patients with darker skin may experience permanent discoloration and may not be good candidates for alternative treatments such as laser therapy due to the risk for inducible hyperpigmentation.⁷

Conclusion

No matter the etiology, EAI usually is a benign skin condition that is treated by removal of the causative heat source. Once a diagnosis is made, the clinician must work with the patient to determine the etiology. Care must be taken to ensure that there are no underlying signs, such as chronic pain or psychiatric illness, that could point to associated conditions. Rarely, sequalae such as cancers have been documented in areas of chronic EAI. Once the heat source is identified and removed, any remaining hyperpigmentation usually will self-resolve over months to years, though this may take longer in patients with darker skin types. If more aggressive treatment is preferred by the patient, laser therapy, topical medications, and oral over-the-counter vitamins have been tried with minimal responses. 

Erythema ab igne (EAI)(also known as toasted skin syndrome) was first described in the British Journal of Dermatology in the 20th century, ¹ though it was known by physicians long before. Reticular netlike skin changes were seen in association with patients who spent extended time directly next to a heat source. This association led to the name of this condition, which literally means “redness by fire.” Indeed, EAI induced by chronic heat exposure has been described across the world for centuries. For example, in the cold regions of northern China, people used to sleep on beds of hot bricks called kang to stay warm at night. The people of India’s Kashmir district carried pots of hot coals called kangri next to the skin under large woven shawls to stay warm. In the past, Irish women often spent much time by a turf- or peat-burning fire. Chronic heat exposure in these cases can lead not only to EAI but also to aggressive types of cancer, often with a latency of 30 years or more. ²

More recently, the invention of home central heating led to a stark decrease in the number of cases associated with combustion-based heat, with a transition to etiologies such as use of hot water bottles, electric blankets, and electric space heaters. Over time, technological advances led to ever-increasing potential causes for EAI, such as laptops or cell phones, car heaters and heated seats, heated blankets,^3,4 infrared lamps for food, and even medical devices such as ultrasound-based heating products and convective temperature management systems for hospitalized patients. As technology evolves, so do the potential causes of EAI, requiring clinicians to diagnose and deduce the cause through a thorough social and medical history as well as a workup on the present illness with considerations for the anatomical location.^5-7 Herein, we describe the etiology of EAI, diagnosis, and treatment options.

Clinical Characteristics

Erythema ab igne begins as mild, transient, and erythematous macules and patches in a reticular pattern that resolve minutes to hours after removal of the heat source. With weeks to months of continued or repeated application of the heat source, the affected area eventually becomes hyperpigmented where there once was erythema (Figures 1 and 2). Sometimes papules, bullae, telangiectasia, and hyperkeratosis also form. The rash usually is asymptomatic, though pain, pruritus, and dysesthesia have been reported.⁷ Dermoscopy of EAI in the hyperpigmented stage can reveal diffuse superficial dark pigmentation, telangiectasia, and mild whitish scaling.⁸ Although the pathogenesis has remained elusive over the years, lesions do seem to be mostly associated with cumulative exposure to heat rather than length of exposure.⁷

Etiology of EAI

Anatomic Location—The affected site depends on the source of heat (Table). Classic examples of this condition include a patient with EAI presenting on the anterior thighs after working in front of a hot oven or a patient with chronic back pain presenting with lower-back EAI secondary to frequent use of a hot water bottle or heating pad.⁷ With evolving technology over the last few decades, new etiologies have become more common—teenagers are presenting with anterior thigh EAI secondary to frequent laptop use^2-29; patients are holding warm cell phones in their pant pockets, leading to unilateral geometric EAI on the anterior thigh (front pocket) or buttock (back pocket)³⁰; plug-in radiators under computer desks are causing EAI on the lower legs^31-34; and automobile seat heaters have been shown to cause EAI on the posterior legs.^5,35-37 Clinicians should consider anatomic location a critical clue for etiology.

Social History—There are rarer and more highly specific causes of EAI than simple heat exposure that can be parsed from a patient’s social history. Occupational exposure has been documented, such as bakers with exposure to ovens, foundry workers with exposure to heated metals, or fast-food workers with chronic exposure to infrared food lamps.^6,7 There also are cultural practices that can cause EAI. For example, the practice of cupping with moxibustion was shown to create a specific pattern in the shape of the cultural tool used.³⁸ When footbaths with Chinese herbal remedies are performed frequently with high heat, they can lead to EAI on the feet with a linear border at the ankles. There also have been reports of kotatsu (heated tables in Japan) leading to lower-body EAI.^39,40 These cultural practices also are more common in patients with darker skin types, which can lead to hyperpigmentation that is difficult to treat, making early diagnosis important.⁷

Medical History—Case reports have shown EAI caused by patients attempting to use heat-based methods for pain relief of an underlying serious disease such as cancer, bowel pathology (abdominal EAI), spinal disc prolapse (midline back EAI),⁴¹ sickle cell anemia, and renal pathology (posterior upper flank EAI).^6,7,40-49 Patients with hypothyroidism or anorexia have been noted to have generalized EAI sparing the face secondary to repeated and extended hot baths or showers.^50-53 One patient with schizophrenia was shown to have associated thermophilia due to a delusion that led the patient to soak in hot baths for long periods of time, leading to EAI.⁵⁴ Finally, all physicians should be aware of iatrogenic causes of EAI, such as use of warming devices, ultrasound-based warming techniques, and laser therapy for lipolysis. Inquire about the patient’s surgical history or intensive care unit stays as well as alternative medicine or chiropractic visits. Obtaining a history of medical procedures can be enlightening when an etiology is not immediately clear.^7,55,56

Diagnosis

Erythema ab igne is a clinical diagnosis based on recognizable cutaneous findings and a clear history of moderate heat exposure. However, when a clinical diagnosis of EAI is not certain (eg, when unable to obtain a clear history from the patient) or when malignant transformation is suspected, a biopsy can be performed. Pathologically, hematoxylin and eosin staining of EAI classically reveals dilated small vascular channels in the superficial dermis, hence a clinically reticular rash; interface dermatitis clinically manifesting as erythema; and pigment incontinence with melanin-laden macrophages consistent with clinical hyperpigmentation. Finally, for unclear reasons, increased numbers of elastic fibers classically are seen in biopsies of EAI.⁷

 

 

Differential Diagnosis

The differential diagnosis for a reticular patch includes livedo reticularis (Figure 3), which usually manifests as a more generalized rash in patients with chronic disease or coagulopathy such as systemic lupus erythematosus, cryoglobulinemia, or Raynaud phenomenon. When differentiating EAI from livedo reticularis or cutis marmorata, consider that both alternative diagnoses are more vascular appearing and are associated with cold exposure rather than heat exposure. In cases that are less reticular, livedo racemosa can be considered in the differential diagnosis. Finally, poikiloderma of Civatte can be reticular, particularly on dermoscopy, but the distribution on the neck with submental sparing should help to distinguish it from EAI unless a heat source around the neck is identified while taking the patient’s history.⁷

In babies, a reticular generalized rash is most likely to be cutis marmorata (Figure 4), which is a physiologic response to cold exposure that resolves with rewarming of the skin. A more serious condition—cutis marmorata telangiectatica congenita (Figure 5)—usually is present at birth, most frequently involves a single extremity, and notably does not resolve with rewarming. This is an important differential for EAI in children because it can be associated with vascular and neurologic anomalies as well as limb asymmetry. Finally, port-wine stains can sometimes be reticular in appearance and can mimic the early erythematous stages of EAI. However, unlike the erythematous stage of EAI, the port-wine stains will be present at birth.⁷

Emerging in 2020, an important differential diagnosis to consider is a cutaneous manifestation of COVID-19 infection. An erythematous, reticular, chilblainlike or transient livedo reticularis–like rash has been described as a cutaneous manifestation of COVID-19. Although the pathophysiology is still being elucidated, it is suspected that this is caused by a major vaso-occlusive crisis secondary to COVID-19–induced thrombotic vasculopathy. Interestingly, the majority of patients with this COVID-related exanthem also displayed symptoms of COVID-19 (eg, fever, cough) at the time of presentation,^57-60 but there also have been cases in patients who were asymptomatic or mildly symptomatic.⁶⁰

In some cases, EAI is an indication to screen for an underlying disease. For example, uncontrolled pain is an opportunity to improve interventions such as modifying the patient’s pain-control regimen, placing a palliative care pain consultation, or checking if the patient has had age-appropriate screenings for malignancy. New focal pain in a patient with a prior diagnosis of cancer may be a sign of a new metastasis. A thermophilic patient leaves opportunity to assess for underlying medical causes such as thyroid abnormalities or social/psychological issues. Geriatric patients who are diagnosed with EAI may need to be assessed for dementia or home safety issues. Patients with a history of diabetes mellitus can unknowingly develop EAI on the lower extremities, which may signal a need to assess the patient for peripheral neuropathy. Patients with gastroparesis secondary to diabetes also may develop EAI on the abdomen secondary to heating pad use for discomfort. These examples are a reminder to consider possible secondary comorbidities in all diagnoses of EAI.⁷ 

Prognosis

Although the prognosis of EAI is excellent if caught early, failure to diagnose this condition can lead to permanent discoloration of the skin and even malignancy.⁶ A rare sequela includes squamous cell carcinoma, most commonly seen in chronic cases of the lower leg, which is likely related to chronic inflammation of the skin.^61-65 Rare cases of poorly differentiated carcinoma,⁶⁶ cutaneous marginal zone lymphoma,⁶⁷ and Merkel cell carcinoma⁶⁸ have been reported. Patients diagnosed with EAI should receive normal periodic surveillance of the skin based on their medical history, though the physician should have an increased suspicion and plan for biopsy of any nodules or ulcerations found on the skin of the affected area.⁷

Treatments

Once the diagnosis of EAI is made, treatment starts with removal of the heat source causing the rash. Because the rash usually is asymptomatic, further treatment typically is not required. The discoloration can resolve over months or years, but permanent hyperpigmentation is not uncommon. If hyperpigmentation persists despite removal of the heat source and the patient desires further treatment for discoloration, there are few treatment options, none of which are approved by the US Food and Drug Administration for this condition.⁷ There is some evidence for the use of Nd:YAG lasers to reduce hyperpigmentation in EAI.⁶⁹ There have been some reports of treatment using topical hydroquinone and topical tretinoin in an attempt to lighten the skin. If associated hyperkeratosis or other epithelial atypia is present, the use of 5-fluorouracil may show some improvement.⁷⁰ One case report has been published of successful treatment with systemic mesoglycan and topical bioflavonoids.⁷¹ It also is conceivable that medications used to treat postinflammatory hyperpigmentation may be helpful in this condition (eg, kojic acid, arbutin, mild topical steroids, azelaic acid). Patients with darker skin may experience permanent discoloration and may not be good candidates for alternative treatments such as laser therapy due to the risk for inducible hyperpigmentation.⁷

Conclusion

No matter the etiology, EAI usually is a benign skin condition that is treated by removal of the causative heat source. Once a diagnosis is made, the clinician must work with the patient to determine the etiology. Care must be taken to ensure that there are no underlying signs, such as chronic pain or psychiatric illness, that could point to associated conditions. Rarely, sequalae such as cancers have been documented in areas of chronic EAI. Once the heat source is identified and removed, any remaining hyperpigmentation usually will self-resolve over months to years, though this may take longer in patients with darker skin types. If more aggressive treatment is preferred by the patient, laser therapy, topical medications, and oral over-the-counter vitamins have been tried with minimal responses. 

Erythema ab igne (EAI)(also known as toasted skin syndrome) was first described in the British Journal of Dermatology in the 20th century, ¹ though it was known by physicians long before. Reticular netlike skin changes were seen in association with patients who spent extended time directly next to a heat source. This association led to the name of this condition, which literally means “redness by fire.” Indeed, EAI induced by chronic heat exposure has been described across the world for centuries. For example, in the cold regions of northern China, people used to sleep on beds of hot bricks called kang to stay warm at night. The people of India’s Kashmir district carried pots of hot coals called kangri next to the skin under large woven shawls to stay warm. In the past, Irish women often spent much time by a turf- or peat-burning fire. Chronic heat exposure in these cases can lead not only to EAI but also to aggressive types of cancer, often with a latency of 30 years or more. ²

More recently, the invention of home central heating led to a stark decrease in the number of cases associated with combustion-based heat, with a transition to etiologies such as use of hot water bottles, electric blankets, and electric space heaters. Over time, technological advances led to ever-increasing potential causes for EAI, such as laptops or cell phones, car heaters and heated seats, heated blankets,^3,4 infrared lamps for food, and even medical devices such as ultrasound-based heating products and convective temperature management systems for hospitalized patients. As technology evolves, so do the potential causes of EAI, requiring clinicians to diagnose and deduce the cause through a thorough social and medical history as well as a workup on the present illness with considerations for the anatomical location.^5-7 Herein, we describe the etiology of EAI, diagnosis, and treatment options.

Clinical Characteristics

Erythema ab igne begins as mild, transient, and erythematous macules and patches in a reticular pattern that resolve minutes to hours after removal of the heat source. With weeks to months of continued or repeated application of the heat source, the affected area eventually becomes hyperpigmented where there once was erythema (Figures 1 and 2). Sometimes papules, bullae, telangiectasia, and hyperkeratosis also form. The rash usually is asymptomatic, though pain, pruritus, and dysesthesia have been reported.⁷ Dermoscopy of EAI in the hyperpigmented stage can reveal diffuse superficial dark pigmentation, telangiectasia, and mild whitish scaling.⁸ Although the pathogenesis has remained elusive over the years, lesions do seem to be mostly associated with cumulative exposure to heat rather than length of exposure.⁷

Etiology of EAI

Anatomic Location—The affected site depends on the source of heat (Table). Classic examples of this condition include a patient with EAI presenting on the anterior thighs after working in front of a hot oven or a patient with chronic back pain presenting with lower-back EAI secondary to frequent use of a hot water bottle or heating pad.⁷ With evolving technology over the last few decades, new etiologies have become more common—teenagers are presenting with anterior thigh EAI secondary to frequent laptop use^2-29; patients are holding warm cell phones in their pant pockets, leading to unilateral geometric EAI on the anterior thigh (front pocket) or buttock (back pocket)³⁰; plug-in radiators under computer desks are causing EAI on the lower legs^31-34; and automobile seat heaters have been shown to cause EAI on the posterior legs.^5,35-37 Clinicians should consider anatomic location a critical clue for etiology.

Social History—There are rarer and more highly specific causes of EAI than simple heat exposure that can be parsed from a patient’s social history. Occupational exposure has been documented, such as bakers with exposure to ovens, foundry workers with exposure to heated metals, or fast-food workers with chronic exposure to infrared food lamps.^6,7 There also are cultural practices that can cause EAI. For example, the practice of cupping with moxibustion was shown to create a specific pattern in the shape of the cultural tool used.³⁸ When footbaths with Chinese herbal remedies are performed frequently with high heat, they can lead to EAI on the feet with a linear border at the ankles. There also have been reports of kotatsu (heated tables in Japan) leading to lower-body EAI.^39,40 These cultural practices also are more common in patients with darker skin types, which can lead to hyperpigmentation that is difficult to treat, making early diagnosis important.⁷

Medical History—Case reports have shown EAI caused by patients attempting to use heat-based methods for pain relief of an underlying serious disease such as cancer, bowel pathology (abdominal EAI), spinal disc prolapse (midline back EAI),⁴¹ sickle cell anemia, and renal pathology (posterior upper flank EAI).^6,7,40-49 Patients with hypothyroidism or anorexia have been noted to have generalized EAI sparing the face secondary to repeated and extended hot baths or showers.^50-53 One patient with schizophrenia was shown to have associated thermophilia due to a delusion that led the patient to soak in hot baths for long periods of time, leading to EAI.⁵⁴ Finally, all physicians should be aware of iatrogenic causes of EAI, such as use of warming devices, ultrasound-based warming techniques, and laser therapy for lipolysis. Inquire about the patient’s surgical history or intensive care unit stays as well as alternative medicine or chiropractic visits. Obtaining a history of medical procedures can be enlightening when an etiology is not immediately clear.^7,55,56

Diagnosis

Erythema ab igne is a clinical diagnosis based on recognizable cutaneous findings and a clear history of moderate heat exposure. However, when a clinical diagnosis of EAI is not certain (eg, when unable to obtain a clear history from the patient) or when malignant transformation is suspected, a biopsy can be performed. Pathologically, hematoxylin and eosin staining of EAI classically reveals dilated small vascular channels in the superficial dermis, hence a clinically reticular rash; interface dermatitis clinically manifesting as erythema; and pigment incontinence with melanin-laden macrophages consistent with clinical hyperpigmentation. Finally, for unclear reasons, increased numbers of elastic fibers classically are seen in biopsies of EAI.⁷

 

 

Differential Diagnosis

The differential diagnosis for a reticular patch includes livedo reticularis (Figure 3), which usually manifests as a more generalized rash in patients with chronic disease or coagulopathy such as systemic lupus erythematosus, cryoglobulinemia, or Raynaud phenomenon. When differentiating EAI from livedo reticularis or cutis marmorata, consider that both alternative diagnoses are more vascular appearing and are associated with cold exposure rather than heat exposure. In cases that are less reticular, livedo racemosa can be considered in the differential diagnosis. Finally, poikiloderma of Civatte can be reticular, particularly on dermoscopy, but the distribution on the neck with submental sparing should help to distinguish it from EAI unless a heat source around the neck is identified while taking the patient’s history.⁷

In babies, a reticular generalized rash is most likely to be cutis marmorata (Figure 4), which is a physiologic response to cold exposure that resolves with rewarming of the skin. A more serious condition—cutis marmorata telangiectatica congenita (Figure 5)—usually is present at birth, most frequently involves a single extremity, and notably does not resolve with rewarming. This is an important differential for EAI in children because it can be associated with vascular and neurologic anomalies as well as limb asymmetry. Finally, port-wine stains can sometimes be reticular in appearance and can mimic the early erythematous stages of EAI. However, unlike the erythematous stage of EAI, the port-wine stains will be present at birth.⁷

Emerging in 2020, an important differential diagnosis to consider is a cutaneous manifestation of COVID-19 infection. An erythematous, reticular, chilblainlike or transient livedo reticularis–like rash has been described as a cutaneous manifestation of COVID-19. Although the pathophysiology is still being elucidated, it is suspected that this is caused by a major vaso-occlusive crisis secondary to COVID-19–induced thrombotic vasculopathy. Interestingly, the majority of patients with this COVID-related exanthem also displayed symptoms of COVID-19 (eg, fever, cough) at the time of presentation,^57-60 but there also have been cases in patients who were asymptomatic or mildly symptomatic.⁶⁰

In some cases, EAI is an indication to screen for an underlying disease. For example, uncontrolled pain is an opportunity to improve interventions such as modifying the patient’s pain-control regimen, placing a palliative care pain consultation, or checking if the patient has had age-appropriate screenings for malignancy. New focal pain in a patient with a prior diagnosis of cancer may be a sign of a new metastasis. A thermophilic patient leaves opportunity to assess for underlying medical causes such as thyroid abnormalities or social/psychological issues. Geriatric patients who are diagnosed with EAI may need to be assessed for dementia or home safety issues. Patients with a history of diabetes mellitus can unknowingly develop EAI on the lower extremities, which may signal a need to assess the patient for peripheral neuropathy. Patients with gastroparesis secondary to diabetes also may develop EAI on the abdomen secondary to heating pad use for discomfort. These examples are a reminder to consider possible secondary comorbidities in all diagnoses of EAI.⁷ 

Prognosis

Although the prognosis of EAI is excellent if caught early, failure to diagnose this condition can lead to permanent discoloration of the skin and even malignancy.⁶ A rare sequela includes squamous cell carcinoma, most commonly seen in chronic cases of the lower leg, which is likely related to chronic inflammation of the skin.^61-65 Rare cases of poorly differentiated carcinoma,⁶⁶ cutaneous marginal zone lymphoma,⁶⁷ and Merkel cell carcinoma⁶⁸ have been reported. Patients diagnosed with EAI should receive normal periodic surveillance of the skin based on their medical history, though the physician should have an increased suspicion and plan for biopsy of any nodules or ulcerations found on the skin of the affected area.⁷

Treatments

Once the diagnosis of EAI is made, treatment starts with removal of the heat source causing the rash. Because the rash usually is asymptomatic, further treatment typically is not required. The discoloration can resolve over months or years, but permanent hyperpigmentation is not uncommon. If hyperpigmentation persists despite removal of the heat source and the patient desires further treatment for discoloration, there are few treatment options, none of which are approved by the US Food and Drug Administration for this condition.⁷ There is some evidence for the use of Nd:YAG lasers to reduce hyperpigmentation in EAI.⁶⁹ There have been some reports of treatment using topical hydroquinone and topical tretinoin in an attempt to lighten the skin. If associated hyperkeratosis or other epithelial atypia is present, the use of 5-fluorouracil may show some improvement.⁷⁰ One case report has been published of successful treatment with systemic mesoglycan and topical bioflavonoids.⁷¹ It also is conceivable that medications used to treat postinflammatory hyperpigmentation may be helpful in this condition (eg, kojic acid, arbutin, mild topical steroids, azelaic acid). Patients with darker skin may experience permanent discoloration and may not be good candidates for alternative treatments such as laser therapy due to the risk for inducible hyperpigmentation.⁷

Conclusion

No matter the etiology, EAI usually is a benign skin condition that is treated by removal of the causative heat source. Once a diagnosis is made, the clinician must work with the patient to determine the etiology. Care must be taken to ensure that there are no underlying signs, such as chronic pain or psychiatric illness, that could point to associated conditions. Rarely, sequalae such as cancers have been documented in areas of chronic EAI. Once the heat source is identified and removed, any remaining hyperpigmentation usually will self-resolve over months to years, though this may take longer in patients with darker skin types. If more aggressive treatment is preferred by the patient, laser therapy, topical medications, and oral over-the-counter vitamins have been tried with minimal responses. 

PHOENIX – Combining a serum containing silymarin with nonablative laser therapy could serve as a promising solution for decreasing inflammation, postinflammatory erythema (PIE), and postinflammatory hyperpigmentation (PIH) associated with acne lesions, results from a prospective, single-center study showed.

“Acne vulgaris is the most common inflammatory dermatosis worldwide, often resulting in sequelae such as scarring, PIE, and PIH,” presenting author Jamie Hu, MD, said at the annual conference of the American Society for Laser Medicine and Surgery, where the study results were presented during an abstract session. “This dyschromia can cause greater psychological distress than the original acne lesions, and disproportionately affects skin of color patients.”

Blemish-prone skin is known to have higher levels of sebum and lower levels of antioxidants, leading to lipid peroxidation and oxidative stress, resulting in proliferation of Cutibacterium acnes and an inflammatory cascade that has recently been implicated in postinflammatory dyschromia and the development of PIE and PIH, noted Dr. Hu, a dermatology resident at the University of Miami. “Therefore, the use of antioxidants presents an opportunity to disrupt blemish and dyschromia,” she said.

One such antioxidant is silymarin, which is derived from the milk thistle plant. Recent studies have demonstrated that silymarin reduces proinflammatory mediators, prevents lipid peroxidation, and presents a new way to target the treatment of both acne and postinflammatory dyschromia.

Dr. Hu’s mentor, Jill S. Waibel, MD, owner and medical director of the Miami Dermatology and Laser Institute, hypothesized that nonablative laser therapy followed by topical application of silymarin would improve acne-associated postinflammatory dyschromia. To test her hunch, she conducted a 12-week, prospective trial in which 24 patients with PIE and/or PIH were randomized to one of two treatment arms: laser treatment with topical antioxidants or laser treatment with vehicle control. Patients received three laser treatments, each 1 month apart. The topical antioxidant used was Silymarin CF, a serum that contains 0.5% silymarin, 0.5% salicylic acid, 15% L-ascorbic acid, and 0.5% ferulic acid. (The study was sponsored by SkinCeuticals, the manufacturer of the serum.)

Laser selection was made primarily on the type of dyschromia, with PIE patients receiving treatment with the pulsed dye laser and PIH patients receiving treatment with the 1,927-nm thulium laser. Patients were treated on days 0, 28, and 56 of the 12-week study, followed by immediate application of topical antioxidants or vehicle control. They were also instructed to apply the assigned topical twice daily for the duration of the study. Patients ranged in age from 21 to 61 years, and 20 had skin types III-IV.

To evaluate efficacy, the researchers conducted blinded clinical assessments with the postacne hyperpigmentation index (PAHPI) and the Global Aesthetic Improvement Scale (GAIS), instrumentation with the Mexameter, a device that captures erythema and melanin index values, and visual diagnostics with optical coherence tomography (OCT).

Dr. Hu reported that at week 12, the PAHPI in the silymarin-plus-laser treatment group fell from an average of 3.18 to 1.74 (a decrease of 1.44), which suggested an improvement trend, compared with the laser treatment–only group, whose PAHPI fell from an average of 3.25 to 1.97 (a decrease of 1.28).

As for the GAIS, a one-time score assessed at the end of the trial, the average score for all patients was 3.24, which translated to “much improved/very much improved.” Patients in the silymarin-plus-laser treatment group had higher average scores compared with patients in the laser treatment–only group (3.35 vs. 3.10, respectively), but the differences did not reach statistical significance.

According to results of the Mexameter assessment, paired t-tests showed that the levels of intralesional melanin decreased significantly for patients in the silymarin-plus-laser treatment group, compared with the laser treatment–only group (P < .05). OCT assessments demonstrated an increase in dermal brightness in both groups, corresponding to an increase in dermal collagen, as well as an increase in blood vessel density.

In an interview at the meeting, Dr. Waibel, subsection chief of dermatology at Baptist Hospital of Miami, said that future studies will focus on long-term follow-up to determine if acne scars can be prevented by combining silymarin with lasers to prevent PIH and PIE. “That would be priceless,” she said. “I believe that the PIH is what causes damage to the collagen, and that damage to the collagen is what causes the scarring. So, if we can prevent or treat PIH, we may be able to prevent scarring.”

This approach, she added, “would decrease the pharmaceutical cost because I think there are many dermatologists who are treating PEI and PIH as active acne. You really have to have a keen eye for understanding the differences and you really have to be looking, because PIE and PIH are flat, whereas active acne consists of either comedones or nodules.”

She noted that in skin of color patients, she has seen PIH persist for 9 or 10 months after treatment with isotretinoin. “It’s not the isotretinoin causing the scars, or even the acne, it’s the prolonged inflammation,” she said.

Catherine M. DiGiorgio, MD, a Boston-based laser and cosmetic dermatologist who was asked to comment on the study, said that patients and dermatologists frequently seek alternatives to hydroquinone for unwanted hyperpigmentation.

Dr. DiGiorgio

Dr. Jalian

“While the study failed to show statistically significant improvement in postinflammatory erythema with concomitant laser and topical therapy versus laser alone, the promising data supporting concurrent use of topicals and fractional lasers for treatment of PIH, particularly in dark skin phototypes, is a clinically impactful contribution to our daily practice,” he said.

Dr. Waibel disclosed that she has conducted clinical trials for many device and pharmaceutical companies including SkinCeuticals. Dr. Hu, Dr. DiGiorgio, and Dr. Jalian were not involved with the study and reported having no relevant disclosures.

PHOENIX – Combining a serum containing silymarin with nonablative laser therapy could serve as a promising solution for decreasing inflammation, postinflammatory erythema (PIE), and postinflammatory hyperpigmentation (PIH) associated with acne lesions, results from a prospective, single-center study showed.

“Acne vulgaris is the most common inflammatory dermatosis worldwide, often resulting in sequelae such as scarring, PIE, and PIH,” presenting author Jamie Hu, MD, said at the annual conference of the American Society for Laser Medicine and Surgery, where the study results were presented during an abstract session. “This dyschromia can cause greater psychological distress than the original acne lesions, and disproportionately affects skin of color patients.”

Blemish-prone skin is known to have higher levels of sebum and lower levels of antioxidants, leading to lipid peroxidation and oxidative stress, resulting in proliferation of Cutibacterium acnes and an inflammatory cascade that has recently been implicated in postinflammatory dyschromia and the development of PIE and PIH, noted Dr. Hu, a dermatology resident at the University of Miami. “Therefore, the use of antioxidants presents an opportunity to disrupt blemish and dyschromia,” she said.

One such antioxidant is silymarin, which is derived from the milk thistle plant. Recent studies have demonstrated that silymarin reduces proinflammatory mediators, prevents lipid peroxidation, and presents a new way to target the treatment of both acne and postinflammatory dyschromia.

Dr. Hu’s mentor, Jill S. Waibel, MD, owner and medical director of the Miami Dermatology and Laser Institute, hypothesized that nonablative laser therapy followed by topical application of silymarin would improve acne-associated postinflammatory dyschromia. To test her hunch, she conducted a 12-week, prospective trial in which 24 patients with PIE and/or PIH were randomized to one of two treatment arms: laser treatment with topical antioxidants or laser treatment with vehicle control. Patients received three laser treatments, each 1 month apart. The topical antioxidant used was Silymarin CF, a serum that contains 0.5% silymarin, 0.5% salicylic acid, 15% L-ascorbic acid, and 0.5% ferulic acid. (The study was sponsored by SkinCeuticals, the manufacturer of the serum.)

Laser selection was made primarily on the type of dyschromia, with PIE patients receiving treatment with the pulsed dye laser and PIH patients receiving treatment with the 1,927-nm thulium laser. Patients were treated on days 0, 28, and 56 of the 12-week study, followed by immediate application of topical antioxidants or vehicle control. They were also instructed to apply the assigned topical twice daily for the duration of the study. Patients ranged in age from 21 to 61 years, and 20 had skin types III-IV.

To evaluate efficacy, the researchers conducted blinded clinical assessments with the postacne hyperpigmentation index (PAHPI) and the Global Aesthetic Improvement Scale (GAIS), instrumentation with the Mexameter, a device that captures erythema and melanin index values, and visual diagnostics with optical coherence tomography (OCT).

Dr. Hu reported that at week 12, the PAHPI in the silymarin-plus-laser treatment group fell from an average of 3.18 to 1.74 (a decrease of 1.44), which suggested an improvement trend, compared with the laser treatment–only group, whose PAHPI fell from an average of 3.25 to 1.97 (a decrease of 1.28).

As for the GAIS, a one-time score assessed at the end of the trial, the average score for all patients was 3.24, which translated to “much improved/very much improved.” Patients in the silymarin-plus-laser treatment group had higher average scores compared with patients in the laser treatment–only group (3.35 vs. 3.10, respectively), but the differences did not reach statistical significance.

According to results of the Mexameter assessment, paired t-tests showed that the levels of intralesional melanin decreased significantly for patients in the silymarin-plus-laser treatment group, compared with the laser treatment–only group (P < .05). OCT assessments demonstrated an increase in dermal brightness in both groups, corresponding to an increase in dermal collagen, as well as an increase in blood vessel density.

In an interview at the meeting, Dr. Waibel, subsection chief of dermatology at Baptist Hospital of Miami, said that future studies will focus on long-term follow-up to determine if acne scars can be prevented by combining silymarin with lasers to prevent PIH and PIE. “That would be priceless,” she said. “I believe that the PIH is what causes damage to the collagen, and that damage to the collagen is what causes the scarring. So, if we can prevent or treat PIH, we may be able to prevent scarring.”

This approach, she added, “would decrease the pharmaceutical cost because I think there are many dermatologists who are treating PEI and PIH as active acne. You really have to have a keen eye for understanding the differences and you really have to be looking, because PIE and PIH are flat, whereas active acne consists of either comedones or nodules.”

She noted that in skin of color patients, she has seen PIH persist for 9 or 10 months after treatment with isotretinoin. “It’s not the isotretinoin causing the scars, or even the acne, it’s the prolonged inflammation,” she said.

Catherine M. DiGiorgio, MD, a Boston-based laser and cosmetic dermatologist who was asked to comment on the study, said that patients and dermatologists frequently seek alternatives to hydroquinone for unwanted hyperpigmentation.

Dr. DiGiorgio

Dr. Jalian

“While the study failed to show statistically significant improvement in postinflammatory erythema with concomitant laser and topical therapy versus laser alone, the promising data supporting concurrent use of topicals and fractional lasers for treatment of PIH, particularly in dark skin phototypes, is a clinically impactful contribution to our daily practice,” he said.

Dr. Waibel disclosed that she has conducted clinical trials for many device and pharmaceutical companies including SkinCeuticals. Dr. Hu, Dr. DiGiorgio, and Dr. Jalian were not involved with the study and reported having no relevant disclosures.

PHOENIX – Combining a serum containing silymarin with nonablative laser therapy could serve as a promising solution for decreasing inflammation, postinflammatory erythema (PIE), and postinflammatory hyperpigmentation (PIH) associated with acne lesions, results from a prospective, single-center study showed.

“Acne vulgaris is the most common inflammatory dermatosis worldwide, often resulting in sequelae such as scarring, PIE, and PIH,” presenting author Jamie Hu, MD, said at the annual conference of the American Society for Laser Medicine and Surgery, where the study results were presented during an abstract session. “This dyschromia can cause greater psychological distress than the original acne lesions, and disproportionately affects skin of color patients.”

Blemish-prone skin is known to have higher levels of sebum and lower levels of antioxidants, leading to lipid peroxidation and oxidative stress, resulting in proliferation of Cutibacterium acnes and an inflammatory cascade that has recently been implicated in postinflammatory dyschromia and the development of PIE and PIH, noted Dr. Hu, a dermatology resident at the University of Miami. “Therefore, the use of antioxidants presents an opportunity to disrupt blemish and dyschromia,” she said.

One such antioxidant is silymarin, which is derived from the milk thistle plant. Recent studies have demonstrated that silymarin reduces proinflammatory mediators, prevents lipid peroxidation, and presents a new way to target the treatment of both acne and postinflammatory dyschromia.

Dr. Hu’s mentor, Jill S. Waibel, MD, owner and medical director of the Miami Dermatology and Laser Institute, hypothesized that nonablative laser therapy followed by topical application of silymarin would improve acne-associated postinflammatory dyschromia. To test her hunch, she conducted a 12-week, prospective trial in which 24 patients with PIE and/or PIH were randomized to one of two treatment arms: laser treatment with topical antioxidants or laser treatment with vehicle control. Patients received three laser treatments, each 1 month apart. The topical antioxidant used was Silymarin CF, a serum that contains 0.5% silymarin, 0.5% salicylic acid, 15% L-ascorbic acid, and 0.5% ferulic acid. (The study was sponsored by SkinCeuticals, the manufacturer of the serum.)

Laser selection was made primarily on the type of dyschromia, with PIE patients receiving treatment with the pulsed dye laser and PIH patients receiving treatment with the 1,927-nm thulium laser. Patients were treated on days 0, 28, and 56 of the 12-week study, followed by immediate application of topical antioxidants or vehicle control. They were also instructed to apply the assigned topical twice daily for the duration of the study. Patients ranged in age from 21 to 61 years, and 20 had skin types III-IV.

To evaluate efficacy, the researchers conducted blinded clinical assessments with the postacne hyperpigmentation index (PAHPI) and the Global Aesthetic Improvement Scale (GAIS), instrumentation with the Mexameter, a device that captures erythema and melanin index values, and visual diagnostics with optical coherence tomography (OCT).

Dr. Hu reported that at week 12, the PAHPI in the silymarin-plus-laser treatment group fell from an average of 3.18 to 1.74 (a decrease of 1.44), which suggested an improvement trend, compared with the laser treatment–only group, whose PAHPI fell from an average of 3.25 to 1.97 (a decrease of 1.28).

As for the GAIS, a one-time score assessed at the end of the trial, the average score for all patients was 3.24, which translated to “much improved/very much improved.” Patients in the silymarin-plus-laser treatment group had higher average scores compared with patients in the laser treatment–only group (3.35 vs. 3.10, respectively), but the differences did not reach statistical significance.

According to results of the Mexameter assessment, paired t-tests showed that the levels of intralesional melanin decreased significantly for patients in the silymarin-plus-laser treatment group, compared with the laser treatment–only group (P < .05). OCT assessments demonstrated an increase in dermal brightness in both groups, corresponding to an increase in dermal collagen, as well as an increase in blood vessel density.

In an interview at the meeting, Dr. Waibel, subsection chief of dermatology at Baptist Hospital of Miami, said that future studies will focus on long-term follow-up to determine if acne scars can be prevented by combining silymarin with lasers to prevent PIH and PIE. “That would be priceless,” she said. “I believe that the PIH is what causes damage to the collagen, and that damage to the collagen is what causes the scarring. So, if we can prevent or treat PIH, we may be able to prevent scarring.”

This approach, she added, “would decrease the pharmaceutical cost because I think there are many dermatologists who are treating PEI and PIH as active acne. You really have to have a keen eye for understanding the differences and you really have to be looking, because PIE and PIH are flat, whereas active acne consists of either comedones or nodules.”

She noted that in skin of color patients, she has seen PIH persist for 9 or 10 months after treatment with isotretinoin. “It’s not the isotretinoin causing the scars, or even the acne, it’s the prolonged inflammation,” she said.

Catherine M. DiGiorgio, MD, a Boston-based laser and cosmetic dermatologist who was asked to comment on the study, said that patients and dermatologists frequently seek alternatives to hydroquinone for unwanted hyperpigmentation.

Dr. DiGiorgio

Dr. Jalian

“While the study failed to show statistically significant improvement in postinflammatory erythema with concomitant laser and topical therapy versus laser alone, the promising data supporting concurrent use of topicals and fractional lasers for treatment of PIH, particularly in dark skin phototypes, is a clinically impactful contribution to our daily practice,” he said.

Dr. Waibel disclosed that she has conducted clinical trials for many device and pharmaceutical companies including SkinCeuticals. Dr. Hu, Dr. DiGiorgio, and Dr. Jalian were not involved with the study and reported having no relevant disclosures.

Taking a swing against arthritis

Osteoarthritis is a tough disease to manage. Exercise helps ease the stiffness and pain of the joints, but at the same time, the disease makes it difficult to do that beneficial exercise. Even a relatively simple activity like jogging can hurt more than it helps. If only there were a low-impact exercise that was incredibly popular among the generally older population who are likely to have arthritis.

We love a good golf study here at LOTME, and a group of Australian and U.K. researchers have provided. Osteoarthritis affects 2 million people in the land down under, making it the most common source of disability there. In that population, only 64% reported their physical health to be good, very good, or excellent. Among the 459 golfers with OA that the study authors surveyed, however, the percentage reporting good health rose to more than 90%.

jacoblund/Getty Images

A similar story emerged when they looked at mental health. Nearly a quarter of nongolfers with OA reported high or very high levels of psychological distress, compared with just 8% of golfers. This pattern of improved physical and mental health remained when the researchers looked at the general, non-OA population.

This isn’t the first time golf’s been connected with improved health, and previous studies have shown golf to reduce the risks of cardiovascular disease, diabetes, and obesity, among other things. Just walking one 18-hole round significantly exceeds the CDC’s recommended 150 minutes of physical activity per week. Go out multiple times a week – leaving the cart and beer at home, American golfers – and you’ll be fit for a lifetime.

The golfers on our staff, however, are still waiting for those mental health benefits to kick in. Because when we’re adding up our scorecard after that string of four double bogeys to end the round, we’re most definitely thinking: “Yes, this sport is reducing my psychological distress. I am having fun right now.”
 

Battle of the sexes’ intestines

There are, we’re sure you’ve noticed, some differences between males and females. Females, for one thing, have longer small intestines than males. Everybody knows that, right? You didn’t know? Really? … Really?

Afif Ramdhasuma/Unsplash

Well, then, we’re guessing you haven’t read “Hidden diversity: Comparative functional morphology of humans and other species” by Erin A. McKenney, PhD, of North Carolina State University, Raleigh, and associates, which just appeared in PeerJ. We couldn’t put it down, even in the shower – a real page-turner/scroller. (It’s a great way to clean a phone, for those who also like to scroll, text, or talk on the toilet.)

The researchers got out their rulers, calipers, and string and took many measurements of the digestive systems of 45 human cadavers (21 female and 24 male), which were compared with data from 10 rats, 10 pigs, and 10 bullfrogs, which had been collected (the measurements, not the animals) by undergraduate students enrolled in a comparative anatomy laboratory course at the university.

There was little intestinal-length variation among the four-legged subjects, but when it comes to humans, females have “consistently and significantly longer small intestines than males,” the investigators noted.

The women’s small intestines, almost 14 feet long on average, were about a foot longer than the men’s, which suggests that women are better able to extract nutrients from food and “supports the canalization hypothesis, which posits that women are better able to survive during periods of stress,” coauthor Amanda Hale said in a written statement from the school. The way to a man’s heart may be through his stomach, but the way to a woman’s heart is through her duodenum, it seems.

Fascinating stuff, to be sure, but the thing that really caught our eye in the PeerJ article was the authors’ suggestion “that organs behave independently of one another, both within and across species.” Organs behaving independently? A somewhat ominous concept, no doubt, but it does explain a lot of the sounds we hear coming from our guts, which can get pretty frightening, especially on chili night.
 

Dog walking is dangerous business

Yes, you did read that right. A lot of strange things can send you to the emergency department. Go ahead and add dog walking onto that list.

Investigators from Johns Hopkins University estimate that over 422,000 adults presented to U.S. emergency departments with leash-dependent dog walking-related injuries between 2001 and 2020.

freestocks/Unsplash

With almost 53% of U.S. households owning at least one dog in 2021-2022 in the wake of the COVID pet boom, this kind of occurrence is becoming more common than you think. The annual number of dog-walking injuries more than quadrupled from 7,300 to 32,000 over the course of the study, and the researchers link that spike to the promotion of dog walking for fitness, along with the boost of ownership itself.

The most common injuries listed in the National Electronic Injury Surveillance System database were finger fracture, traumatic brain injury, and shoulder sprain or strain. These mostly involved falls from being pulled, tripped, or tangled up in the leash while walking. For those aged 65 years and older, traumatic brain injury and hip fracture were the most common.

Women were 50% more likely to sustain a fracture than were men, and dog owners aged 65 and older were three times as likely to fall, twice as likely to get a fracture, and 60% more likely to have brain injury than were younger people. Now, that’s not to say younger people don’t also get hurt. After all, dogs aren’t ageists. The researchers have that data but it’s coming out later.

Meanwhile, the pitfalls involved with just trying to get our daily steps in while letting Muffin do her business have us on the lookout for random squirrels.

Taking a swing against arthritis

Osteoarthritis is a tough disease to manage. Exercise helps ease the stiffness and pain of the joints, but at the same time, the disease makes it difficult to do that beneficial exercise. Even a relatively simple activity like jogging can hurt more than it helps. If only there were a low-impact exercise that was incredibly popular among the generally older population who are likely to have arthritis.

We love a good golf study here at LOTME, and a group of Australian and U.K. researchers have provided. Osteoarthritis affects 2 million people in the land down under, making it the most common source of disability there. In that population, only 64% reported their physical health to be good, very good, or excellent. Among the 459 golfers with OA that the study authors surveyed, however, the percentage reporting good health rose to more than 90%.

jacoblund/Getty Images

A similar story emerged when they looked at mental health. Nearly a quarter of nongolfers with OA reported high or very high levels of psychological distress, compared with just 8% of golfers. This pattern of improved physical and mental health remained when the researchers looked at the general, non-OA population.

This isn’t the first time golf’s been connected with improved health, and previous studies have shown golf to reduce the risks of cardiovascular disease, diabetes, and obesity, among other things. Just walking one 18-hole round significantly exceeds the CDC’s recommended 150 minutes of physical activity per week. Go out multiple times a week – leaving the cart and beer at home, American golfers – and you’ll be fit for a lifetime.

The golfers on our staff, however, are still waiting for those mental health benefits to kick in. Because when we’re adding up our scorecard after that string of four double bogeys to end the round, we’re most definitely thinking: “Yes, this sport is reducing my psychological distress. I am having fun right now.”
 

Battle of the sexes’ intestines

There are, we’re sure you’ve noticed, some differences between males and females. Females, for one thing, have longer small intestines than males. Everybody knows that, right? You didn’t know? Really? … Really?

Afif Ramdhasuma/Unsplash

Well, then, we’re guessing you haven’t read “Hidden diversity: Comparative functional morphology of humans and other species” by Erin A. McKenney, PhD, of North Carolina State University, Raleigh, and associates, which just appeared in PeerJ. We couldn’t put it down, even in the shower – a real page-turner/scroller. (It’s a great way to clean a phone, for those who also like to scroll, text, or talk on the toilet.)

The researchers got out their rulers, calipers, and string and took many measurements of the digestive systems of 45 human cadavers (21 female and 24 male), which were compared with data from 10 rats, 10 pigs, and 10 bullfrogs, which had been collected (the measurements, not the animals) by undergraduate students enrolled in a comparative anatomy laboratory course at the university.

There was little intestinal-length variation among the four-legged subjects, but when it comes to humans, females have “consistently and significantly longer small intestines than males,” the investigators noted.

The women’s small intestines, almost 14 feet long on average, were about a foot longer than the men’s, which suggests that women are better able to extract nutrients from food and “supports the canalization hypothesis, which posits that women are better able to survive during periods of stress,” coauthor Amanda Hale said in a written statement from the school. The way to a man’s heart may be through his stomach, but the way to a woman’s heart is through her duodenum, it seems.

Fascinating stuff, to be sure, but the thing that really caught our eye in the PeerJ article was the authors’ suggestion “that organs behave independently of one another, both within and across species.” Organs behaving independently? A somewhat ominous concept, no doubt, but it does explain a lot of the sounds we hear coming from our guts, which can get pretty frightening, especially on chili night.
 

Dog walking is dangerous business

Yes, you did read that right. A lot of strange things can send you to the emergency department. Go ahead and add dog walking onto that list.

Investigators from Johns Hopkins University estimate that over 422,000 adults presented to U.S. emergency departments with leash-dependent dog walking-related injuries between 2001 and 2020.

freestocks/Unsplash

With almost 53% of U.S. households owning at least one dog in 2021-2022 in the wake of the COVID pet boom, this kind of occurrence is becoming more common than you think. The annual number of dog-walking injuries more than quadrupled from 7,300 to 32,000 over the course of the study, and the researchers link that spike to the promotion of dog walking for fitness, along with the boost of ownership itself.

The most common injuries listed in the National Electronic Injury Surveillance System database were finger fracture, traumatic brain injury, and shoulder sprain or strain. These mostly involved falls from being pulled, tripped, or tangled up in the leash while walking. For those aged 65 years and older, traumatic brain injury and hip fracture were the most common.

Women were 50% more likely to sustain a fracture than were men, and dog owners aged 65 and older were three times as likely to fall, twice as likely to get a fracture, and 60% more likely to have brain injury than were younger people. Now, that’s not to say younger people don’t also get hurt. After all, dogs aren’t ageists. The researchers have that data but it’s coming out later.

Meanwhile, the pitfalls involved with just trying to get our daily steps in while letting Muffin do her business have us on the lookout for random squirrels.

Taking a swing against arthritis

Osteoarthritis is a tough disease to manage. Exercise helps ease the stiffness and pain of the joints, but at the same time, the disease makes it difficult to do that beneficial exercise. Even a relatively simple activity like jogging can hurt more than it helps. If only there were a low-impact exercise that was incredibly popular among the generally older population who are likely to have arthritis.

We love a good golf study here at LOTME, and a group of Australian and U.K. researchers have provided. Osteoarthritis affects 2 million people in the land down under, making it the most common source of disability there. In that population, only 64% reported their physical health to be good, very good, or excellent. Among the 459 golfers with OA that the study authors surveyed, however, the percentage reporting good health rose to more than 90%.

jacoblund/Getty Images

A similar story emerged when they looked at mental health. Nearly a quarter of nongolfers with OA reported high or very high levels of psychological distress, compared with just 8% of golfers. This pattern of improved physical and mental health remained when the researchers looked at the general, non-OA population.

This isn’t the first time golf’s been connected with improved health, and previous studies have shown golf to reduce the risks of cardiovascular disease, diabetes, and obesity, among other things. Just walking one 18-hole round significantly exceeds the CDC’s recommended 150 minutes of physical activity per week. Go out multiple times a week – leaving the cart and beer at home, American golfers – and you’ll be fit for a lifetime.

The golfers on our staff, however, are still waiting for those mental health benefits to kick in. Because when we’re adding up our scorecard after that string of four double bogeys to end the round, we’re most definitely thinking: “Yes, this sport is reducing my psychological distress. I am having fun right now.”
 

Battle of the sexes’ intestines

There are, we’re sure you’ve noticed, some differences between males and females. Females, for one thing, have longer small intestines than males. Everybody knows that, right? You didn’t know? Really? … Really?

Afif Ramdhasuma/Unsplash

Well, then, we’re guessing you haven’t read “Hidden diversity: Comparative functional morphology of humans and other species” by Erin A. McKenney, PhD, of North Carolina State University, Raleigh, and associates, which just appeared in PeerJ. We couldn’t put it down, even in the shower – a real page-turner/scroller. (It’s a great way to clean a phone, for those who also like to scroll, text, or talk on the toilet.)

The researchers got out their rulers, calipers, and string and took many measurements of the digestive systems of 45 human cadavers (21 female and 24 male), which were compared with data from 10 rats, 10 pigs, and 10 bullfrogs, which had been collected (the measurements, not the animals) by undergraduate students enrolled in a comparative anatomy laboratory course at the university.

There was little intestinal-length variation among the four-legged subjects, but when it comes to humans, females have “consistently and significantly longer small intestines than males,” the investigators noted.

The women’s small intestines, almost 14 feet long on average, were about a foot longer than the men’s, which suggests that women are better able to extract nutrients from food and “supports the canalization hypothesis, which posits that women are better able to survive during periods of stress,” coauthor Amanda Hale said in a written statement from the school. The way to a man’s heart may be through his stomach, but the way to a woman’s heart is through her duodenum, it seems.

Fascinating stuff, to be sure, but the thing that really caught our eye in the PeerJ article was the authors’ suggestion “that organs behave independently of one another, both within and across species.” Organs behaving independently? A somewhat ominous concept, no doubt, but it does explain a lot of the sounds we hear coming from our guts, which can get pretty frightening, especially on chili night.
 

Dog walking is dangerous business

Yes, you did read that right. A lot of strange things can send you to the emergency department. Go ahead and add dog walking onto that list.

Investigators from Johns Hopkins University estimate that over 422,000 adults presented to U.S. emergency departments with leash-dependent dog walking-related injuries between 2001 and 2020.

freestocks/Unsplash

With almost 53% of U.S. households owning at least one dog in 2021-2022 in the wake of the COVID pet boom, this kind of occurrence is becoming more common than you think. The annual number of dog-walking injuries more than quadrupled from 7,300 to 32,000 over the course of the study, and the researchers link that spike to the promotion of dog walking for fitness, along with the boost of ownership itself.

The most common injuries listed in the National Electronic Injury Surveillance System database were finger fracture, traumatic brain injury, and shoulder sprain or strain. These mostly involved falls from being pulled, tripped, or tangled up in the leash while walking. For those aged 65 years and older, traumatic brain injury and hip fracture were the most common.

Women were 50% more likely to sustain a fracture than were men, and dog owners aged 65 and older were three times as likely to fall, twice as likely to get a fracture, and 60% more likely to have brain injury than were younger people. Now, that’s not to say younger people don’t also get hurt. After all, dogs aren’t ageists. The researchers have that data but it’s coming out later.

Meanwhile, the pitfalls involved with just trying to get our daily steps in while letting Muffin do her business have us on the lookout for random squirrels.

PHOENIX – When Kathy Givens walked onstage during a plenary session at the annual conference of the American Society for Laser Medicine and Surgery to reflect on her 9-month ordeal being sex trafficked in Texas more than 20 years ago, you could hear a pin drop.

“One of the scariest things about the life of sex trafficking is not knowing who’s going to be on the other side,” said Ms. Givens, who now lives in Houston. “There was some violence. There were some horrible things that happened. But you know what was really scary? When I got out. People may ask, ‘How’s that so? You escaped your trafficker. The past is behind you. Why were you afraid?’ I was afraid because I didn’t know that I had community. I didn’t know that community or that society would care about someone like me.”

Doug Brunk/MDedge News

She said that she found herself immobilized by fear of being shamed in society and labeled a sex trafficking victim, and wondered if she could overcome that fear and if anyone would view her as human again. Once free from her trafficker, she began a “healing journey,” which included getting married, raising four children, and re-enrolling in college with hopes of becoming a social worker. In 2020, she and her husband founded Twelve 11 Partners, an organization committed to supporting human trafficking survivors.

“I was working in the anti-trafficking field helping other survivors ... who have experienced this horrific crime,” she said. “I thought I was on my way.” But one “stain” from her sex trafficking past remained: The name of her trafficker was tattooed on her skin, “a reminder of what I’d gone through.”

Ms. Givens was eventually introduced to Paul M. Friedman, MD, the current ASLMS president and one of the nearly 90 physicians in the United States and Canada who perform tattoo removal free of charge for trafficking survivors as part of the New Beginnings: Tattoo Removal Program, a partnership between the ASLMS and the National Trafficking Sheltered Alliance (NTSA) that was formed in 2022. According to a survey that Dr. Friedman and colleagues presented at the 2022 annual ASLMS conference, an estimated 1 in 2 sex trafficking survivors have branding tattoos, and at least 1,000 survivors a year could benefit from removal of those tattoos.

“To date, 87 physicians in the U.S. and one in Canada have stepped forward to volunteer their services to be part of this program,” Dr. Friedman, who directs the Dermatology and Laser Surgery Center in Houston, said at this year’s meeting. “My goal is to double this number by the next annual conference,” he added, noting that trauma-informed training is part of the program, “to support the survivor experience during the treatment process.”

ASLMS is also working on this issue in partnership with the American Academy of Dermatology (AAD) Ad Hoc Task Force on Dermatological Resources for the Intervention and Prevention of Human Trafficking, which is headed by Boston dermatologist Shadi Kourosh, MD.

“Dermatologists are uniquely positioned to aid in efforts to assist those experiences in trafficking with our training to recognize and diagnose relevant signs on the skin and to assist patients with certain aspects of care and recovery including the treatment of the disease of scars and tattoos,” Dr. Friedman said. “Ultimately, we hope to create a database together to improve recognition of branding tattoos to aid in identifying sex trafficking victims.”

Ms. Givens, who sits on the U.S. Advisory Council on Human Trafficking, said that she was able to truly close the door on her sex trafficking past thanks to the tattoo removal Dr. Friedman performed as part of New Beginnings. “It means the world to me to know that I can now be an advocate for other individuals who have experienced human trafficking,” she told meeting attendees.

“Again, one of the scariest things is not knowing that you have community. I was scared of losing hope, but I’m standing here today. I have all the hope that I need. You have the power to change lives.”

PHOENIX – When Kathy Givens walked onstage during a plenary session at the annual conference of the American Society for Laser Medicine and Surgery to reflect on her 9-month ordeal being sex trafficked in Texas more than 20 years ago, you could hear a pin drop.

“One of the scariest things about the life of sex trafficking is not knowing who’s going to be on the other side,” said Ms. Givens, who now lives in Houston. “There was some violence. There were some horrible things that happened. But you know what was really scary? When I got out. People may ask, ‘How’s that so? You escaped your trafficker. The past is behind you. Why were you afraid?’ I was afraid because I didn’t know that I had community. I didn’t know that community or that society would care about someone like me.”

Doug Brunk/MDedge News

She said that she found herself immobilized by fear of being shamed in society and labeled a sex trafficking victim, and wondered if she could overcome that fear and if anyone would view her as human again. Once free from her trafficker, she began a “healing journey,” which included getting married, raising four children, and re-enrolling in college with hopes of becoming a social worker. In 2020, she and her husband founded Twelve 11 Partners, an organization committed to supporting human trafficking survivors.

“I was working in the anti-trafficking field helping other survivors ... who have experienced this horrific crime,” she said. “I thought I was on my way.” But one “stain” from her sex trafficking past remained: The name of her trafficker was tattooed on her skin, “a reminder of what I’d gone through.”

Ms. Givens was eventually introduced to Paul M. Friedman, MD, the current ASLMS president and one of the nearly 90 physicians in the United States and Canada who perform tattoo removal free of charge for trafficking survivors as part of the New Beginnings: Tattoo Removal Program, a partnership between the ASLMS and the National Trafficking Sheltered Alliance (NTSA) that was formed in 2022. According to a survey that Dr. Friedman and colleagues presented at the 2022 annual ASLMS conference, an estimated 1 in 2 sex trafficking survivors have branding tattoos, and at least 1,000 survivors a year could benefit from removal of those tattoos.

“To date, 87 physicians in the U.S. and one in Canada have stepped forward to volunteer their services to be part of this program,” Dr. Friedman, who directs the Dermatology and Laser Surgery Center in Houston, said at this year’s meeting. “My goal is to double this number by the next annual conference,” he added, noting that trauma-informed training is part of the program, “to support the survivor experience during the treatment process.”

ASLMS is also working on this issue in partnership with the American Academy of Dermatology (AAD) Ad Hoc Task Force on Dermatological Resources for the Intervention and Prevention of Human Trafficking, which is headed by Boston dermatologist Shadi Kourosh, MD.

“Dermatologists are uniquely positioned to aid in efforts to assist those experiences in trafficking with our training to recognize and diagnose relevant signs on the skin and to assist patients with certain aspects of care and recovery including the treatment of the disease of scars and tattoos,” Dr. Friedman said. “Ultimately, we hope to create a database together to improve recognition of branding tattoos to aid in identifying sex trafficking victims.”

Ms. Givens, who sits on the U.S. Advisory Council on Human Trafficking, said that she was able to truly close the door on her sex trafficking past thanks to the tattoo removal Dr. Friedman performed as part of New Beginnings. “It means the world to me to know that I can now be an advocate for other individuals who have experienced human trafficking,” she told meeting attendees.

“Again, one of the scariest things is not knowing that you have community. I was scared of losing hope, but I’m standing here today. I have all the hope that I need. You have the power to change lives.”

PHOENIX – When Kathy Givens walked onstage during a plenary session at the annual conference of the American Society for Laser Medicine and Surgery to reflect on her 9-month ordeal being sex trafficked in Texas more than 20 years ago, you could hear a pin drop.

“One of the scariest things about the life of sex trafficking is not knowing who’s going to be on the other side,” said Ms. Givens, who now lives in Houston. “There was some violence. There were some horrible things that happened. But you know what was really scary? When I got out. People may ask, ‘How’s that so? You escaped your trafficker. The past is behind you. Why were you afraid?’ I was afraid because I didn’t know that I had community. I didn’t know that community or that society would care about someone like me.”

Doug Brunk/MDedge News

She said that she found herself immobilized by fear of being shamed in society and labeled a sex trafficking victim, and wondered if she could overcome that fear and if anyone would view her as human again. Once free from her trafficker, she began a “healing journey,” which included getting married, raising four children, and re-enrolling in college with hopes of becoming a social worker. In 2020, she and her husband founded Twelve 11 Partners, an organization committed to supporting human trafficking survivors.

“I was working in the anti-trafficking field helping other survivors ... who have experienced this horrific crime,” she said. “I thought I was on my way.” But one “stain” from her sex trafficking past remained: The name of her trafficker was tattooed on her skin, “a reminder of what I’d gone through.”

Ms. Givens was eventually introduced to Paul M. Friedman, MD, the current ASLMS president and one of the nearly 90 physicians in the United States and Canada who perform tattoo removal free of charge for trafficking survivors as part of the New Beginnings: Tattoo Removal Program, a partnership between the ASLMS and the National Trafficking Sheltered Alliance (NTSA) that was formed in 2022. According to a survey that Dr. Friedman and colleagues presented at the 2022 annual ASLMS conference, an estimated 1 in 2 sex trafficking survivors have branding tattoos, and at least 1,000 survivors a year could benefit from removal of those tattoos.

“To date, 87 physicians in the U.S. and one in Canada have stepped forward to volunteer their services to be part of this program,” Dr. Friedman, who directs the Dermatology and Laser Surgery Center in Houston, said at this year’s meeting. “My goal is to double this number by the next annual conference,” he added, noting that trauma-informed training is part of the program, “to support the survivor experience during the treatment process.”

ASLMS is also working on this issue in partnership with the American Academy of Dermatology (AAD) Ad Hoc Task Force on Dermatological Resources for the Intervention and Prevention of Human Trafficking, which is headed by Boston dermatologist Shadi Kourosh, MD.

“Dermatologists are uniquely positioned to aid in efforts to assist those experiences in trafficking with our training to recognize and diagnose relevant signs on the skin and to assist patients with certain aspects of care and recovery including the treatment of the disease of scars and tattoos,” Dr. Friedman said. “Ultimately, we hope to create a database together to improve recognition of branding tattoos to aid in identifying sex trafficking victims.”

Ms. Givens, who sits on the U.S. Advisory Council on Human Trafficking, said that she was able to truly close the door on her sex trafficking past thanks to the tattoo removal Dr. Friedman performed as part of New Beginnings. “It means the world to me to know that I can now be an advocate for other individuals who have experienced human trafficking,” she told meeting attendees.

“Again, one of the scariest things is not knowing that you have community. I was scared of losing hope, but I’m standing here today. I have all the hope that I need. You have the power to change lives.”

COVID-19 is a potentially severe systemic disease caused by SARS-CoV-2. SARS-CoV and Middle East respiratory syndrome (MERS-CoV) caused fatal epidemics in Asia in 2002 to 2003 and in the Arabian Peninsula in 2012, respectively. In 2019, SARS-CoV-2 was detected in patients with severe, sometimes fatal pneumonia of previously unknown origin; it rapidly spread around the world, and the World Health Organization declared the disease a pandemic on March 11, 2020. SARS-CoV-2 is a β-coronavirus that is genetically related to the bat coronavirus and SARS-CoV; it is a single-stranded RNA virus of which several variants and subvariants exist. The SARS-CoV-2 viral particles bind via their surface spike protein (S protein) to the angiotensin-converting enzyme 2 receptor present on the membrane of several cell types, including epidermal and adnexal keratinocytes.^1,2 The α and δ variants, predominant from 2020 to 2021, mainly affected the lower respiratory tract and caused severe, potentially fatal pneumonia, especially in patients older than 65 years and/or with comorbidities, such as obesity, hypertension, diabetes, and (iatrogenic) immunosuppression. The ο variant, which appeared in late 2021, is more contagious than the initial variants, but it causes a less severe disease preferentially affecting the upper respiratory airways.³ As of April 5, 2023, more than 762,000,000 confirmed cases of COVID-19 have been recorded worldwide, causing more than 6,800,000 deaths.⁴

Early studies from China describing the symptoms of COVID-19 reported a low frequency of skin manifestations (0.2%), probably because they were focused on the most severe disease symptoms.⁵ Subsequently, when COVID-19 spread to the rest of the world, an increasing number of skin manifestations were reported in association with the disease. After the first publication from northern Italy in spring 2020, which was specifically devoted to skin manifestations of COVID-19,⁶ an explosive number of publications reported a large number of skin manifestations, and national registries were established in several countries to record these manifestations, such as the American Academy of Dermatology and the International League of Dermatological Societies registry,^7,8 the COVIDSKIN registry of the French Dermatology Society,⁹ and the Italian registry.¹⁰ Highlighting the unprecedented number of scientific articles published on this new disease, a PubMed search of articles indexed for MEDLINE search using the terms SARS-CoV-2 or COVID-19, on April 6, 2023, revealed 351,596 articles; that is more than 300 articles published every day in this database alone, with a large number of them concerning the skin.

SKIN DISEASSES ASSOCIATED WITH COVID-19

There are several types of COVID-19–related skin manifestations, depending on the circumstances of onset and the evolution of the pandemic.

Skin Manifestations Associated With SARS-CoV-2 Infection

The estimated incidence varies greatly according to the published series of patients, possibly depending on the geographic location. The estimated incidence seems lower in Asian countries, such as China (0.2%)⁵ and Japan (0.56%),¹¹ compared with Europe (up to 20%).⁶ Skin manifestations associated with SARS-CoV-2 infection affect individuals of all ages, slightly more females, and are clinically polymorphous; some of them are associated with the severity of the infection.¹² They may precede, accompany, or appear after the symptoms of COVID-19, most often within a month of the infection, of which they rarely are the only manifestation; however, their precise relationship to SARS-CoV-2 is not always well known. They have been classified according to their clinical presentation into several forms.^13-15

Morbilliform Maculopapular Eruption—Representing 16% to 53% of skin manifestations, morbilliform and maculopapular eruptions usually appear within 15 days of infection; they manifest with more or less confluent erythematous macules that may be hemorrhagic/petechial, and usually are asymptomatic and rarely pruritic. The rash mainly affects the trunk and limbs, sparing the face, palmoplantar regions, and mucous membranes; it appears concomitantly with or a few days after the first symptoms of COVID-19 (eg, fever, respiratory symptoms), regresses within a few days, and does not appear to be associated with disease severity. The distinction from maculopapular drug eruptions may be subtle. Histologically, the rash manifests with a spongiform dermatitis (ie, variable parakeratosis; spongiosis; and a mixed dermal perivascular infiltrate of lymphocytes, eosinophils and histiocytes, depending on the lesion age)(Figure 1). The etiopathogenesis is unknown; it may involve immune complexes to SARS-CoV-2 deposited on skin vessels. Treatment is not mandatory; if necessary, local or systemic corticosteroids may be used.

Vesicular (Pseudovaricella) Rash—This rash accounts for 11% to 18% of all skin manifestations and usually appears within 15 days of COVID-19 onset. It manifests with small monomorphous or varicellalike (pseudopolymorphic) vesicles appearing on the trunk, usually in young patients. The vesicles may be herpetiform, hemorrhagic, or pruritic, and appear before or within 3 days of the onset of mild COVID-19 symptoms; they regress within a few days without scarring. Histologically, the lesions show basal cell vacuolization; multinucleated, dyskeratotic/apoptotic or ballooning/acantholytic epidermal keratinocytes; reticular degeneration of the epidermis; intraepidermal vesicles sometimes resembling herpetic vesicular infections or Grover disease; and mild dermal inflammation. There is no specific treatment.

Urticaria—Urticarial rash, or urticaria, represents 5% to 16% of skin manifestations; usually appears within 15 days of disease onset; and manifests with pruritic, migratory, edematous papules appearing mainly on the trunk and occasionally the face and limbs. The urticarial rash tends to be associated with more severe forms of the disease and regresses within a week, responding to antihistamines. Of note, clinically similar rashes can be caused by drugs. Histologically, the lesions show dermal edema and a mild perivascular lymphocytic infiltrate, sometimes admixed with eosinophils.

Chilblainlike Lesions—Chilblainlike lesions (CBLLs) account for 19% of skin manifestations associated with COVID-19¹³ and present as erythematous-purplish, edematous lesions that can be mildly pruritic or painful, appearing on the toes—COVID toes—and more rarely the fingers (Figure 2). They were seen epidemically during the first pandemic wave (2020 lockdown) in several countries, and clinically are very similar to, if not indistinguishable from, idiopathic chilblains, but are not necessarily associated with cold exposure. They appear in young, generally healthy patients or those with mild COVID-19 symptoms 2 to 4 weeks after symptom onset. They regress spontaneously or under local corticosteroid treatment within a few days or weeks. Histologically, CBLLs are indistinguishable from chilblains of other origins, namely idiopathic (seasonal) ones. They manifest with necrosis of epidermal keratinocytes; dermal edema that may be severe, leading to the development of subepidermal pseudobullae; a rather dense perivascular and perieccrine gland lymphocytic infiltrate; and sometimes with vascular lesions (eg, edema of endothelial cells, microthromboses of dermal capillaries and venules, fibrinoid deposits within the wall of dermal venules)(Figure 3).^16-18 Most patients (>80%) with CBLLs have negative serologic or polymerase chain reaction tests for SARS-CoV-2,¹⁹ which generated a lively debate about the role of SARS-CoV-2 in the genesis of CBLLs. According to some authors, SARS-CoV-2 plays no direct role, and CBLLs would occur in young people who sit or walk barefoot on cold floors at home during confinement.^20-23 Remarkably, CBLLs appeared in patients with no history of chilblains during a season that was not particularly cold, namely in France or in southern California, where their incidence was much higher compared to the same time period of prior years. Some reports have supported a direct role for the virus based on questionable observations of the virus within skin lesions (eg, sweat glands, endothelial cells) by immunohistochemistry, electron microscopy, and/or in situ hybridization.^17,24,25 A more satisfactory hypothesis would involve the role of a strong innate immunity leading to elimination of the virus before the development of specific antibodies via the increased production of type 1 interferon (IFN-1); this would affect the vessels, causing CBLLs. This mechanism would be similar to the one observed in some interferonopathies (eg, Aicardi-Goutières syndrome), also characterized by IFN-1 hypersecretion and chilblains.^26-29 According to this hypothesis, CBLLs should be considered a paraviral rash similar to other skin manifestations associated with COVID-19.³⁰

Acro-ischemia—Acro-ischemia livedoid lesions account for 1% to 6% of skin manifestations and comprise lesions of livedo (either reticulated or racemosa); necrotic acral bullae; and gangrenous necrosis of the extremities, especially the toes. The livedoid lesions most often appear within 15 days of COVID-19 symptom onset, and the purpuric lesions somewhat later (2–4 weeks); they mainly affect adult patients, last about 10 days, and are the hallmark of severe infection, presumably related to microthromboses of the cutaneous capillaries (endothelial dysfunction, prothrombotic state, elevated D-dimers). Histologically, they show capillary thrombosis and dermoepidermal necrosis (Figure 4).

Other Reported Polymorphic or Atypical Rashes—Erythema multiforme–like eruptions may appear before other COVID-19 symptoms and manifest as reddish-purple, nearly symmetric, diffuse, occasionally targetoid bullous or necrotic macules. The eruptions mainly affect adults and most often are seen on the palms, elbows, knees, and sometimes the mucous membranes. The rash regresses in 1 to 3 weeks without scarring and represents a delayed cutaneous hypersensitivity reaction. Histologically, the lesions show vacuolization of basal epidermal keratinocytes, keratinocyte necrosis, dermoepidermal detachment, a variably dense dermal T-lymphocytic infiltrate, and red blood cell extravasation (Figure 5).

Leukocytoclastic vasculitis may be generalized or localized. It manifests clinically by petechial/purpuric maculopapules, especially on the legs, mainly in elderly patients with COVID-19. Histologically, the lesions show necrotizing changes of dermal postcapillary venules, neutrophilic perivascular inflammation, red blood cell extravasation, and occasionally vascular IgA deposits by direct immunofluorescence examination. The course usually is benign.

The incidence of pityriasis rosea and of clinically similar rashes (referred to as “pityriasis rosea–like”) increased 5-fold during the COVID-19 pandemic.^31,32 These dermatoses manifest with erythematous, scaly, circinate plaques, typically with an initial herald lesion followed a few days later by smaller erythematous macules. Histologically, the lesions comprise a spongiform dermatitis with intraepidermal exocytosis of red blood cells and a mild to moderate dermal lymphocytic infiltrate.

Erythrodysesthesia, or hand-foot syndrome, manifests with edematous erythema and palmoplantar desquamation accompanied by a burning sensation or pain. This syndrome is known as an adverse effect of some chemotherapies because of the associated drug toxicity and sweat gland inflammation; it was observed in 40% of 666 COVID-19–positive patients with mild to moderate pneumonitis.³³

“COVID nose” is a rare cutaneous manifestation characterized by nasal pigmentation comprising multiple coalescent frecklelike macules on the tip and wings of the nose and sometimes the malar areas. These lesions predominantly appear in women aged 25 to 65 years and show on average 23 days after onset of COVID-19, which is usually mild. This pigmentation is similar to pigmentary changes after infection with chikungunya; it can be treated with depigmenting products such as azelaic acid and hydroquinone cream with sunscreen use, and it regresses in 2 to 4 months.³⁴

Telogen effluvium (excessive and temporary shedding of normal telogen club hairs of the entire scalp due to the disturbance of the hair cycle) is reportedly frequent in patients (48%) 1 month after COVID-19 infection, but it may appear later (after 12 weeks).³⁵ Alopecia also is frequently reported during long (or postacute) COVID-19 (ie, the symptomatic disease phase past the acute 4 weeks’ stage of the infection) and shows a female predominance³⁶; it likely represents the telogen effluvium seen 90 days after a severe illness. Trichodynia (pruritus, burning, pain, or paresthesia of the scalp) also is reportedly common (developing in more than 58% of patients) and is associated with telogen effluvium in 44% of cases. Several cases of alopecia areata (AA) triggered or aggravated by COVID-19 also have been reported^37,38; they could be explained by the “cytokine storm” triggered by the infection, involving T and B lymphocytes; plasmacytoid dendritic cells; natural killer cells with oversecretion of IL-6, IL-4, tumor necrosis factor α, and IFN type I; and a cytotoxic reaction associated with loss of the immune privilege of hair follicles.

Nail Manifestations

The red half-moon nail sign is an asymptomatic purplish-red band around the distal margin of the lunula that affects some adult patients with COVID-19.³⁹ It appears shortly after onset of symptoms, likely the manifestation of vascular inflammation in the nail bed, and regresses slowly after approximately 1 week.⁴⁰ Beau lines are transverse grooves in the nail plate due to the temporary arrest of the proximal nail matrix growth accompanying systemic illnesses; they appear approximately 2 to 3 weeks after the onset of COVID-19.⁴¹ Furthermore, nail alterations can be caused by drugs used to treat COVID-19, such as longitudinal melanonychia due to treatment with hydroxychloroquine or fluorescence of the lunula or nail plate due to treatment with favipiravir.⁴²

Multisystem Inflammatory Syndrome

Multisystem inflammatory syndrome (MIS) is clinically similar to Kawasaki disease; it typically affects children⁴³ and more rarely adults with COVID-19. It manifests with fever, weakness, and biological inflammation and also frequently with skin lesions (72%), which are polymorphous and include morbilliform rash (27%); urticaria (24%); periorbital edema (24%); nonspecific erythema (21.2%); retiform purpura (18%); targetoid lesions (15%); malar rash (15.2%); and periareolar erythema (6%).⁴⁴ Compared to Kawasaki disease, MIS affects slightly older children (mean age, 8.5 vs 3 years) and more frequently includes cardiac and gastrointestinal manifestations; the mortality rate also is slightly higher (2% vs 0.17%).⁴⁵

Confirmed COVID-19 Infection

At the beginning of the pandemic, skin manifestations were reported in patients who were suspected of having COVID-19 but did not always have biological confirmation of SARS-CoV-2 infection due to the unavailability of diagnostic tests or the physical impossibility of testing. However, subsequent studies have confirmed that most of these dermatoses were indeed associated with COVID-19 infection.^9,46 For example, a study of 655 patients with confirmed COVID-19 infection reported maculopapular (38%), vascular (22%), urticarial (15%), and vesicular (15%) rashes; erythema multiforme or Stevens-Johnson–like syndrome (3%, often related to the use of hydroxychloroquine); generalized pruritus (1%); and MIS (0.5%). The study confirmed that CBLLs were mostly seen in young patients with mild disease, whereas livedo (fixed rash) and retiform purpura occurred in older patients with a guarded prognosis.⁴⁶

Remarkably, most dermatoses associated with SARS-CoV-2 infection were reported during the initial waves of the pandemic, which were due to the α and δ viral variants. These manifestations were reported more rarely when the ο variant was predominant, even though most patients (63%) who developed CBLLs in the first wave also developed them during the second pandemic wave.⁴⁷ This decrease in the incidence of COVID-19–associated dermatoses could be because of the lower pathogenicity of the o variant,³ a lower tropism for the skin, and variations in SARS-CoV-2 antigenicity that would induce a different immunologic response, combined with an increasingly stronger herd immunity compared to the first pandemic waves achieved through vaccination and spontaneous infections in the population. Additional reasons may include different baseline characteristics in patients hospitalized with COVID-19 (regarding comorbidities, disease severity, and received treatments), and the possibility that some of the initially reported COVID-19–associated skin manifestations could have been produced by different etiologic agents.⁴⁸ In the last 2 years, COVID-19–related skin manifestations have been reported mainly as adverse events to COVID-19 vaccination.

CUTANEOUS ADVERSE EFFECTS OF DRUGS USED TO TREAT COVID-19

Prior to the advent of vaccines and specific treatments for SARS-CoV-2, various drugs were used—namely hydroxychloroquine, ivermectin, and tocilizumab—that did not prove efficacious and caused diverse adverse effects, including cutaneous eruptions such as urticaria, maculopapular eruptions, erythema multiforme or Stevens-Johnson syndrome, vasculitis, longitudinal melanonychia, and acute generalized exanthematous pustulosis.^49,50 Nirmatrelvir 150 mg–ritonavir 100 mg, which was authorized for emergency use by the US Food and Drug Administration for the treatment of COVID-19, is a viral protease inhibitor blocking the replication of the virus. Ritonavir can induce pruritus, maculopapular rash, acne, Stevens-Johnson syndrome, and toxic epidermal necrolysis; of note, these effects have been observed following administration of ritonavir for treatment of HIV at higher daily doses and for much longer periods of time compared with treatment of COVID-19 (600–1200 mg vs 200 mg/d, respectively). These cutaneous drug side effects are clinically similar to the manifestations caused either directly or indirectly by SARS-CoV-2 infection; therefore, it may be difficult to differentiate them.

DERMATOSES DUE TO PROTECTIVE DEVICES

Dermatoses due to personal protective equipment such as masks or face shields affected the general population and mostly health care professionals⁵¹; 54.4% of 879 health care professionals in one study reported such events.⁵² These dermatoses mainly include contact dermatitis of the face (nose, forehead, and cheeks) of irritant or allergic nature (eg, from preservatives releasing formaldehyde contained in masks and protective goggles). They manifest with skin dryness; desquamation; maceration; fissures; or erosions or ulcerations of the cheeks, forehead, and nose. Cases of pressure urticaria also have been reported. Irritant dermatitis induced by the frequent use of disinfectants (eg, soaps, hydroalcoholic sanitizing gels) also can affect the hands. Allergic hand dermatitis can be caused by medical gloves.

The term maskne (or mask acne) refers to a variety of mechanical acne due to the prolonged use of surgical masks (>4 hours per day for ≥6 weeks); it includes cases of de novo acne and cases of pre-existing acne aggravated by wearing a mask. Maskne is characterized by acne lesions located on the facial area covered by the mask (Figure 6). It is caused by follicular occlusion; increased sebum secretion; mechanical stress (pressure, friction); and dysbiosis of the microbiome induced by changes in heat, pH, and humidity. Preventive measures include application of noncomedogenic moisturizers or gauze before wearing the mask as well as facial cleansing with appropriate nonalcoholic products. Similar to acne, rosacea often is aggravated by prolonged wearing of surgical masks (mask rosacea).^53,54

DERMATOSES REVEALED OR AGGRAVATED BY COVID-19

Exacerbation of various skin diseases has been reported after infection with SARS-CoV-2.⁵⁵ Psoriasis and acrodermatitis continua of Hallopeau,⁵⁶ which may progress into generalized, pustular, or erythrodermic forms,⁵⁷ have been reported; the role of hydroxychloroquine and oral corticosteroids used for the treatment of COVID-19 has been suspected.⁵⁷ Atopic dermatitis patients—26% to 43%—have experienced worsening of their disease after symptomatic COVID-19 infection.⁵⁸ The incidence of herpesvirus infections, including herpes zoster, increased during the pandemic.⁵⁹ Alopecia areata relapses occurred in 42.5% of 392 patients with preexisting disease within 2 months of COVID-19 onset in one study,⁶⁰ possibly favored by the psychological stress; however, some studies have not confirmed the aggravating role of COVID-19 on alopecia areata.⁶¹ Lupus erythematosus, which may relapse in the form of Rowell syndrome,⁶² and livedoid vasculopathy⁶³ also have been reported following COVID-19 infection.

SKIN MANIFESTATIONS ASSOCIATED WITH COVID-19 VACCINES

In parallel with the rapid spread of COVID-19 vaccination,⁴ an increasing number of skin manifestations has been observed following vaccination; these dermatoses now are more frequently reported than those related to natural SARS-CoV-2 infection.^64-70 Vaccine-induced skin manifestations have a reported incidence of approximately 4% and show a female predominance.⁶⁵ Most of them (79%) have been reported in association with messenger RNA (mRNA)–based vaccines, which have been the most widely used; however, the frequency of side effects would be lower after mRNA vaccines than after inactivated virus-based vaccines. Eighteen percent occurred after the adenoviral vector vaccine, and 3% after the inactivated virus vaccine.⁷⁰ Fifty-nine percent were observed after the first dose. They are clinically polymorphous and generally benign, regressing spontaneously after a few days, and they should not constitute a contraindication to vaccination.Interestingly, many skin manifestations are similar to those associated with natural SARS-CoV-2 infection; however, their frequency and severity does not seem to depend on whether the patients had developed skin reactions during prior SARS-CoV-2 infection. These reactions have been classified into several types:

• Immediate local reactions at the injection site: pain, erythema, or edema represent the vast majority (96%) of reactions to vaccines. They appear within 7 days after vaccination (average, 1 day), slightly more frequently (59%) after the first dose. They concern mostly young patients and are benign, regressing in 2 to 3 days.⁷⁰
 

• Delayed local reactions: characterized by pain or pruritus, erythema, and skin induration mimicking cellulitis (COVID arm) and represent 1.7% of postvaccination reactions. They correspond to a delayed hypersensitivity reaction and appear approximately 7 days after vaccination, most often after the first vaccine dose (75% of cases), which is almost invariably mRNA based.⁷⁰

• Urticarial reactions corresponding to an immediate (type 1) hypersensitivity reaction: constitute 1% of postvaccination reactions, probably due to an allergy to vaccine ingredients. They appear on average 1 day after vaccination, almost always with mRNA vaccines.⁷⁰

• Angioedema: characterized by mucosal or subcutaneous edema and constitutes 0.5% of postvaccination reactions. It is a potentially serious reaction that appears on average 12 hours after vaccination, always with an mRNA-based vaccine.⁷⁰

• Morbilliform rash: represents delayed hypersensitivity reactions (0.1% of postvaccination reactions) that appear mostly after the first dose (72%), on average 3 days after vaccination, always with an mRNA-based vaccine.⁷⁰

• Herpes zoster: usually develops after the first vaccine dose in elderly patients (69% of cases) on average 4 days after vaccination and constitutes 0.1% of postvaccination reactions.⁷¹

• Bullous diseases: mainly bullous pemphigoid (90%) and more rarely pemphigus (5%) or bullous erythema pigmentosum (5%). They appear in elderly patients on average 7 days after vaccination and constitute 0.04% of postvaccination reactions.⁷²

• Chilblainlike lesions: several such cases have been reported so far⁷³; they constitute 0.03% of postvaccination reactions.⁷⁰ Clinically, they are similar to those associated with natural COVID-19; they appear mostly after the first dose (64%), on average 5 days after vaccination with the mRNA or adenovirus vaccine, and show a female predominance. The appearance of these lesions in vaccinated patients, who are a priori not carriers of the virus, strongly suggests that CBLLs are due to the immune reaction against SARS-CoV-2 rather than to a direct effect of this virus on the skin, which also is a likely scenario with regards to other skin manifestations seen during the successive COVID-19 epidemic waves.^73-75

• Reactions to hyaluronic acid–containing cosmetic fillers: erythema, edema, and potentially painful induration at the filler injection sites. They constitute 0.04% of postvaccination skin reactions and appear 24 hours after vaccination with mRNA-based vaccines, equally after the first or second dose.⁷⁶

• Pityriasis rosea–like rash: most occur after the second dose of mRNA-based vaccines (0.023% of postvaccination skin reactions).⁷⁰

• Severe reactions: these include acute generalized exanthematous pustulosis⁷⁷ and Stevens-Johnson syndrome.⁷⁸ One case of each has been reported after the adenoviral vector vaccine 3 days after vaccination.

Other more rarely observed manifestations include reactivation/aggravation or de novo appearance of inflammatory dermatoses such as psoriasis,^79,80 leukocytoclastic vasculitis,^81,82 lymphocytic⁸³ or urticarial⁸⁴ vasculitis, Sweet syndrome,⁸⁵ lupus erythematosus, dermatomyositis,^86,87 alopecia,^37,88 infection with Trichophyton rubrum,⁸⁹ Grover disease,⁹⁰ and lymphomatoid reactions (such as recurrences of cutaneous T-cell lymphomas [CD30⁺], and de novo development of lymphomatoid papulosis).⁹¹

FINAL THOUGHTS

COVID-19 is associated with several skin manifestations, even though the causative role of SARS-CoV-2 has remained elusive. These dermatoses are highly polymorphous, mostly benign, and usually spontaneously regressive, but some of them reflect severe infection. They mostly were described during the first pandemic waves, reported in several national and international registries, which allowed for their morphological classification. Currently, cutaneous adverse effects of vaccines are the most frequently reported dermatoses associated with SARS-CoV-2, and it is likely that they will continue to be observed while COVID-19 vaccination lasts. Hopefully the end of the COVID-19 pandemic is near. In January 2023, the International Health Regulations Emergency Committee of the World Health Organization acknowledged that the COVID-19 pandemic may be approaching an inflexion point, and even though the event continues to constitute a public health emergency of international concern, the higher levels of population immunity achieved globally through infection and/or vaccination may limit the impact of SARS-CoV-2 on morbidity and mortality. However, there is little doubt that this virus will remain a permanently established pathogen in humans and animals for the foreseeable future.⁹² Therefore, physicians—especially dermatologists—should be aware of the various skin manifestations associated with COVID-19 so they can more efficiently manage their patients.

COVID-19 is a potentially severe systemic disease caused by SARS-CoV-2. SARS-CoV and Middle East respiratory syndrome (MERS-CoV) caused fatal epidemics in Asia in 2002 to 2003 and in the Arabian Peninsula in 2012, respectively. In 2019, SARS-CoV-2 was detected in patients with severe, sometimes fatal pneumonia of previously unknown origin; it rapidly spread around the world, and the World Health Organization declared the disease a pandemic on March 11, 2020. SARS-CoV-2 is a β-coronavirus that is genetically related to the bat coronavirus and SARS-CoV; it is a single-stranded RNA virus of which several variants and subvariants exist. The SARS-CoV-2 viral particles bind via their surface spike protein (S protein) to the angiotensin-converting enzyme 2 receptor present on the membrane of several cell types, including epidermal and adnexal keratinocytes.^1,2 The α and δ variants, predominant from 2020 to 2021, mainly affected the lower respiratory tract and caused severe, potentially fatal pneumonia, especially in patients older than 65 years and/or with comorbidities, such as obesity, hypertension, diabetes, and (iatrogenic) immunosuppression. The ο variant, which appeared in late 2021, is more contagious than the initial variants, but it causes a less severe disease preferentially affecting the upper respiratory airways.³ As of April 5, 2023, more than 762,000,000 confirmed cases of COVID-19 have been recorded worldwide, causing more than 6,800,000 deaths.⁴

Early studies from China describing the symptoms of COVID-19 reported a low frequency of skin manifestations (0.2%), probably because they were focused on the most severe disease symptoms.⁵ Subsequently, when COVID-19 spread to the rest of the world, an increasing number of skin manifestations were reported in association with the disease. After the first publication from northern Italy in spring 2020, which was specifically devoted to skin manifestations of COVID-19,⁶ an explosive number of publications reported a large number of skin manifestations, and national registries were established in several countries to record these manifestations, such as the American Academy of Dermatology and the International League of Dermatological Societies registry,^7,8 the COVIDSKIN registry of the French Dermatology Society,⁹ and the Italian registry.¹⁰ Highlighting the unprecedented number of scientific articles published on this new disease, a PubMed search of articles indexed for MEDLINE search using the terms SARS-CoV-2 or COVID-19, on April 6, 2023, revealed 351,596 articles; that is more than 300 articles published every day in this database alone, with a large number of them concerning the skin.

SKIN DISEASSES ASSOCIATED WITH COVID-19

There are several types of COVID-19–related skin manifestations, depending on the circumstances of onset and the evolution of the pandemic.

Skin Manifestations Associated With SARS-CoV-2 Infection

The estimated incidence varies greatly according to the published series of patients, possibly depending on the geographic location. The estimated incidence seems lower in Asian countries, such as China (0.2%)⁵ and Japan (0.56%),¹¹ compared with Europe (up to 20%).⁶ Skin manifestations associated with SARS-CoV-2 infection affect individuals of all ages, slightly more females, and are clinically polymorphous; some of them are associated with the severity of the infection.¹² They may precede, accompany, or appear after the symptoms of COVID-19, most often within a month of the infection, of which they rarely are the only manifestation; however, their precise relationship to SARS-CoV-2 is not always well known. They have been classified according to their clinical presentation into several forms.^13-15

Morbilliform Maculopapular Eruption—Representing 16% to 53% of skin manifestations, morbilliform and maculopapular eruptions usually appear within 15 days of infection; they manifest with more or less confluent erythematous macules that may be hemorrhagic/petechial, and usually are asymptomatic and rarely pruritic. The rash mainly affects the trunk and limbs, sparing the face, palmoplantar regions, and mucous membranes; it appears concomitantly with or a few days after the first symptoms of COVID-19 (eg, fever, respiratory symptoms), regresses within a few days, and does not appear to be associated with disease severity. The distinction from maculopapular drug eruptions may be subtle. Histologically, the rash manifests with a spongiform dermatitis (ie, variable parakeratosis; spongiosis; and a mixed dermal perivascular infiltrate of lymphocytes, eosinophils and histiocytes, depending on the lesion age)(Figure 1). The etiopathogenesis is unknown; it may involve immune complexes to SARS-CoV-2 deposited on skin vessels. Treatment is not mandatory; if necessary, local or systemic corticosteroids may be used.

Vesicular (Pseudovaricella) Rash—This rash accounts for 11% to 18% of all skin manifestations and usually appears within 15 days of COVID-19 onset. It manifests with small monomorphous or varicellalike (pseudopolymorphic) vesicles appearing on the trunk, usually in young patients. The vesicles may be herpetiform, hemorrhagic, or pruritic, and appear before or within 3 days of the onset of mild COVID-19 symptoms; they regress within a few days without scarring. Histologically, the lesions show basal cell vacuolization; multinucleated, dyskeratotic/apoptotic or ballooning/acantholytic epidermal keratinocytes; reticular degeneration of the epidermis; intraepidermal vesicles sometimes resembling herpetic vesicular infections or Grover disease; and mild dermal inflammation. There is no specific treatment.

Urticaria—Urticarial rash, or urticaria, represents 5% to 16% of skin manifestations; usually appears within 15 days of disease onset; and manifests with pruritic, migratory, edematous papules appearing mainly on the trunk and occasionally the face and limbs. The urticarial rash tends to be associated with more severe forms of the disease and regresses within a week, responding to antihistamines. Of note, clinically similar rashes can be caused by drugs. Histologically, the lesions show dermal edema and a mild perivascular lymphocytic infiltrate, sometimes admixed with eosinophils.

Chilblainlike Lesions—Chilblainlike lesions (CBLLs) account for 19% of skin manifestations associated with COVID-19¹³ and present as erythematous-purplish, edematous lesions that can be mildly pruritic or painful, appearing on the toes—COVID toes—and more rarely the fingers (Figure 2). They were seen epidemically during the first pandemic wave (2020 lockdown) in several countries, and clinically are very similar to, if not indistinguishable from, idiopathic chilblains, but are not necessarily associated with cold exposure. They appear in young, generally healthy patients or those with mild COVID-19 symptoms 2 to 4 weeks after symptom onset. They regress spontaneously or under local corticosteroid treatment within a few days or weeks. Histologically, CBLLs are indistinguishable from chilblains of other origins, namely idiopathic (seasonal) ones. They manifest with necrosis of epidermal keratinocytes; dermal edema that may be severe, leading to the development of subepidermal pseudobullae; a rather dense perivascular and perieccrine gland lymphocytic infiltrate; and sometimes with vascular lesions (eg, edema of endothelial cells, microthromboses of dermal capillaries and venules, fibrinoid deposits within the wall of dermal venules)(Figure 3).^16-18 Most patients (>80%) with CBLLs have negative serologic or polymerase chain reaction tests for SARS-CoV-2,¹⁹ which generated a lively debate about the role of SARS-CoV-2 in the genesis of CBLLs. According to some authors, SARS-CoV-2 plays no direct role, and CBLLs would occur in young people who sit or walk barefoot on cold floors at home during confinement.^20-23 Remarkably, CBLLs appeared in patients with no history of chilblains during a season that was not particularly cold, namely in France or in southern California, where their incidence was much higher compared to the same time period of prior years. Some reports have supported a direct role for the virus based on questionable observations of the virus within skin lesions (eg, sweat glands, endothelial cells) by immunohistochemistry, electron microscopy, and/or in situ hybridization.^17,24,25 A more satisfactory hypothesis would involve the role of a strong innate immunity leading to elimination of the virus before the development of specific antibodies via the increased production of type 1 interferon (IFN-1); this would affect the vessels, causing CBLLs. This mechanism would be similar to the one observed in some interferonopathies (eg, Aicardi-Goutières syndrome), also characterized by IFN-1 hypersecretion and chilblains.^26-29 According to this hypothesis, CBLLs should be considered a paraviral rash similar to other skin manifestations associated with COVID-19.³⁰

Acro-ischemia—Acro-ischemia livedoid lesions account for 1% to 6% of skin manifestations and comprise lesions of livedo (either reticulated or racemosa); necrotic acral bullae; and gangrenous necrosis of the extremities, especially the toes. The livedoid lesions most often appear within 15 days of COVID-19 symptom onset, and the purpuric lesions somewhat later (2–4 weeks); they mainly affect adult patients, last about 10 days, and are the hallmark of severe infection, presumably related to microthromboses of the cutaneous capillaries (endothelial dysfunction, prothrombotic state, elevated D-dimers). Histologically, they show capillary thrombosis and dermoepidermal necrosis (Figure 4).

Other Reported Polymorphic or Atypical Rashes—Erythema multiforme–like eruptions may appear before other COVID-19 symptoms and manifest as reddish-purple, nearly symmetric, diffuse, occasionally targetoid bullous or necrotic macules. The eruptions mainly affect adults and most often are seen on the palms, elbows, knees, and sometimes the mucous membranes. The rash regresses in 1 to 3 weeks without scarring and represents a delayed cutaneous hypersensitivity reaction. Histologically, the lesions show vacuolization of basal epidermal keratinocytes, keratinocyte necrosis, dermoepidermal detachment, a variably dense dermal T-lymphocytic infiltrate, and red blood cell extravasation (Figure 5).

Leukocytoclastic vasculitis may be generalized or localized. It manifests clinically by petechial/purpuric maculopapules, especially on the legs, mainly in elderly patients with COVID-19. Histologically, the lesions show necrotizing changes of dermal postcapillary venules, neutrophilic perivascular inflammation, red blood cell extravasation, and occasionally vascular IgA deposits by direct immunofluorescence examination. The course usually is benign.

The incidence of pityriasis rosea and of clinically similar rashes (referred to as “pityriasis rosea–like”) increased 5-fold during the COVID-19 pandemic.^31,32 These dermatoses manifest with erythematous, scaly, circinate plaques, typically with an initial herald lesion followed a few days later by smaller erythematous macules. Histologically, the lesions comprise a spongiform dermatitis with intraepidermal exocytosis of red blood cells and a mild to moderate dermal lymphocytic infiltrate.

Erythrodysesthesia, or hand-foot syndrome, manifests with edematous erythema and palmoplantar desquamation accompanied by a burning sensation or pain. This syndrome is known as an adverse effect of some chemotherapies because of the associated drug toxicity and sweat gland inflammation; it was observed in 40% of 666 COVID-19–positive patients with mild to moderate pneumonitis.³³

“COVID nose” is a rare cutaneous manifestation characterized by nasal pigmentation comprising multiple coalescent frecklelike macules on the tip and wings of the nose and sometimes the malar areas. These lesions predominantly appear in women aged 25 to 65 years and show on average 23 days after onset of COVID-19, which is usually mild. This pigmentation is similar to pigmentary changes after infection with chikungunya; it can be treated with depigmenting products such as azelaic acid and hydroquinone cream with sunscreen use, and it regresses in 2 to 4 months.³⁴

Telogen effluvium (excessive and temporary shedding of normal telogen club hairs of the entire scalp due to the disturbance of the hair cycle) is reportedly frequent in patients (48%) 1 month after COVID-19 infection, but it may appear later (after 12 weeks).³⁵ Alopecia also is frequently reported during long (or postacute) COVID-19 (ie, the symptomatic disease phase past the acute 4 weeks’ stage of the infection) and shows a female predominance³⁶; it likely represents the telogen effluvium seen 90 days after a severe illness. Trichodynia (pruritus, burning, pain, or paresthesia of the scalp) also is reportedly common (developing in more than 58% of patients) and is associated with telogen effluvium in 44% of cases. Several cases of alopecia areata (AA) triggered or aggravated by COVID-19 also have been reported^37,38; they could be explained by the “cytokine storm” triggered by the infection, involving T and B lymphocytes; plasmacytoid dendritic cells; natural killer cells with oversecretion of IL-6, IL-4, tumor necrosis factor α, and IFN type I; and a cytotoxic reaction associated with loss of the immune privilege of hair follicles.

Nail Manifestations

The red half-moon nail sign is an asymptomatic purplish-red band around the distal margin of the lunula that affects some adult patients with COVID-19.³⁹ It appears shortly after onset of symptoms, likely the manifestation of vascular inflammation in the nail bed, and regresses slowly after approximately 1 week.⁴⁰ Beau lines are transverse grooves in the nail plate due to the temporary arrest of the proximal nail matrix growth accompanying systemic illnesses; they appear approximately 2 to 3 weeks after the onset of COVID-19.⁴¹ Furthermore, nail alterations can be caused by drugs used to treat COVID-19, such as longitudinal melanonychia due to treatment with hydroxychloroquine or fluorescence of the lunula or nail plate due to treatment with favipiravir.⁴²

Multisystem Inflammatory Syndrome

Multisystem inflammatory syndrome (MIS) is clinically similar to Kawasaki disease; it typically affects children⁴³ and more rarely adults with COVID-19. It manifests with fever, weakness, and biological inflammation and also frequently with skin lesions (72%), which are polymorphous and include morbilliform rash (27%); urticaria (24%); periorbital edema (24%); nonspecific erythema (21.2%); retiform purpura (18%); targetoid lesions (15%); malar rash (15.2%); and periareolar erythema (6%).⁴⁴ Compared to Kawasaki disease, MIS affects slightly older children (mean age, 8.5 vs 3 years) and more frequently includes cardiac and gastrointestinal manifestations; the mortality rate also is slightly higher (2% vs 0.17%).⁴⁵

Confirmed COVID-19 Infection

At the beginning of the pandemic, skin manifestations were reported in patients who were suspected of having COVID-19 but did not always have biological confirmation of SARS-CoV-2 infection due to the unavailability of diagnostic tests or the physical impossibility of testing. However, subsequent studies have confirmed that most of these dermatoses were indeed associated with COVID-19 infection.^9,46 For example, a study of 655 patients with confirmed COVID-19 infection reported maculopapular (38%), vascular (22%), urticarial (15%), and vesicular (15%) rashes; erythema multiforme or Stevens-Johnson–like syndrome (3%, often related to the use of hydroxychloroquine); generalized pruritus (1%); and MIS (0.5%). The study confirmed that CBLLs were mostly seen in young patients with mild disease, whereas livedo (fixed rash) and retiform purpura occurred in older patients with a guarded prognosis.⁴⁶

Remarkably, most dermatoses associated with SARS-CoV-2 infection were reported during the initial waves of the pandemic, which were due to the α and δ viral variants. These manifestations were reported more rarely when the ο variant was predominant, even though most patients (63%) who developed CBLLs in the first wave also developed them during the second pandemic wave.⁴⁷ This decrease in the incidence of COVID-19–associated dermatoses could be because of the lower pathogenicity of the o variant,³ a lower tropism for the skin, and variations in SARS-CoV-2 antigenicity that would induce a different immunologic response, combined with an increasingly stronger herd immunity compared to the first pandemic waves achieved through vaccination and spontaneous infections in the population. Additional reasons may include different baseline characteristics in patients hospitalized with COVID-19 (regarding comorbidities, disease severity, and received treatments), and the possibility that some of the initially reported COVID-19–associated skin manifestations could have been produced by different etiologic agents.⁴⁸ In the last 2 years, COVID-19–related skin manifestations have been reported mainly as adverse events to COVID-19 vaccination.

CUTANEOUS ADVERSE EFFECTS OF DRUGS USED TO TREAT COVID-19

Prior to the advent of vaccines and specific treatments for SARS-CoV-2, various drugs were used—namely hydroxychloroquine, ivermectin, and tocilizumab—that did not prove efficacious and caused diverse adverse effects, including cutaneous eruptions such as urticaria, maculopapular eruptions, erythema multiforme or Stevens-Johnson syndrome, vasculitis, longitudinal melanonychia, and acute generalized exanthematous pustulosis.^49,50 Nirmatrelvir 150 mg–ritonavir 100 mg, which was authorized for emergency use by the US Food and Drug Administration for the treatment of COVID-19, is a viral protease inhibitor blocking the replication of the virus. Ritonavir can induce pruritus, maculopapular rash, acne, Stevens-Johnson syndrome, and toxic epidermal necrolysis; of note, these effects have been observed following administration of ritonavir for treatment of HIV at higher daily doses and for much longer periods of time compared with treatment of COVID-19 (600–1200 mg vs 200 mg/d, respectively). These cutaneous drug side effects are clinically similar to the manifestations caused either directly or indirectly by SARS-CoV-2 infection; therefore, it may be difficult to differentiate them.

DERMATOSES DUE TO PROTECTIVE DEVICES

Dermatoses due to personal protective equipment such as masks or face shields affected the general population and mostly health care professionals⁵¹; 54.4% of 879 health care professionals in one study reported such events.⁵² These dermatoses mainly include contact dermatitis of the face (nose, forehead, and cheeks) of irritant or allergic nature (eg, from preservatives releasing formaldehyde contained in masks and protective goggles). They manifest with skin dryness; desquamation; maceration; fissures; or erosions or ulcerations of the cheeks, forehead, and nose. Cases of pressure urticaria also have been reported. Irritant dermatitis induced by the frequent use of disinfectants (eg, soaps, hydroalcoholic sanitizing gels) also can affect the hands. Allergic hand dermatitis can be caused by medical gloves.

The term maskne (or mask acne) refers to a variety of mechanical acne due to the prolonged use of surgical masks (>4 hours per day for ≥6 weeks); it includes cases of de novo acne and cases of pre-existing acne aggravated by wearing a mask. Maskne is characterized by acne lesions located on the facial area covered by the mask (Figure 6). It is caused by follicular occlusion; increased sebum secretion; mechanical stress (pressure, friction); and dysbiosis of the microbiome induced by changes in heat, pH, and humidity. Preventive measures include application of noncomedogenic moisturizers or gauze before wearing the mask as well as facial cleansing with appropriate nonalcoholic products. Similar to acne, rosacea often is aggravated by prolonged wearing of surgical masks (mask rosacea).^53,54

DERMATOSES REVEALED OR AGGRAVATED BY COVID-19

Exacerbation of various skin diseases has been reported after infection with SARS-CoV-2.⁵⁵ Psoriasis and acrodermatitis continua of Hallopeau,⁵⁶ which may progress into generalized, pustular, or erythrodermic forms,⁵⁷ have been reported; the role of hydroxychloroquine and oral corticosteroids used for the treatment of COVID-19 has been suspected.⁵⁷ Atopic dermatitis patients—26% to 43%—have experienced worsening of their disease after symptomatic COVID-19 infection.⁵⁸ The incidence of herpesvirus infections, including herpes zoster, increased during the pandemic.⁵⁹ Alopecia areata relapses occurred in 42.5% of 392 patients with preexisting disease within 2 months of COVID-19 onset in one study,⁶⁰ possibly favored by the psychological stress; however, some studies have not confirmed the aggravating role of COVID-19 on alopecia areata.⁶¹ Lupus erythematosus, which may relapse in the form of Rowell syndrome,⁶² and livedoid vasculopathy⁶³ also have been reported following COVID-19 infection.

SKIN MANIFESTATIONS ASSOCIATED WITH COVID-19 VACCINES

In parallel with the rapid spread of COVID-19 vaccination,⁴ an increasing number of skin manifestations has been observed following vaccination; these dermatoses now are more frequently reported than those related to natural SARS-CoV-2 infection.^64-70 Vaccine-induced skin manifestations have a reported incidence of approximately 4% and show a female predominance.⁶⁵ Most of them (79%) have been reported in association with messenger RNA (mRNA)–based vaccines, which have been the most widely used; however, the frequency of side effects would be lower after mRNA vaccines than after inactivated virus-based vaccines. Eighteen percent occurred after the adenoviral vector vaccine, and 3% after the inactivated virus vaccine.⁷⁰ Fifty-nine percent were observed after the first dose. They are clinically polymorphous and generally benign, regressing spontaneously after a few days, and they should not constitute a contraindication to vaccination.Interestingly, many skin manifestations are similar to those associated with natural SARS-CoV-2 infection; however, their frequency and severity does not seem to depend on whether the patients had developed skin reactions during prior SARS-CoV-2 infection. These reactions have been classified into several types:

• Immediate local reactions at the injection site: pain, erythema, or edema represent the vast majority (96%) of reactions to vaccines. They appear within 7 days after vaccination (average, 1 day), slightly more frequently (59%) after the first dose. They concern mostly young patients and are benign, regressing in 2 to 3 days.⁷⁰
 

• Delayed local reactions: characterized by pain or pruritus, erythema, and skin induration mimicking cellulitis (COVID arm) and represent 1.7% of postvaccination reactions. They correspond to a delayed hypersensitivity reaction and appear approximately 7 days after vaccination, most often after the first vaccine dose (75% of cases), which is almost invariably mRNA based.⁷⁰

• Urticarial reactions corresponding to an immediate (type 1) hypersensitivity reaction: constitute 1% of postvaccination reactions, probably due to an allergy to vaccine ingredients. They appear on average 1 day after vaccination, almost always with mRNA vaccines.⁷⁰

• Angioedema: characterized by mucosal or subcutaneous edema and constitutes 0.5% of postvaccination reactions. It is a potentially serious reaction that appears on average 12 hours after vaccination, always with an mRNA-based vaccine.⁷⁰

• Morbilliform rash: represents delayed hypersensitivity reactions (0.1% of postvaccination reactions) that appear mostly after the first dose (72%), on average 3 days after vaccination, always with an mRNA-based vaccine.⁷⁰

• Herpes zoster: usually develops after the first vaccine dose in elderly patients (69% of cases) on average 4 days after vaccination and constitutes 0.1% of postvaccination reactions.⁷¹

• Bullous diseases: mainly bullous pemphigoid (90%) and more rarely pemphigus (5%) or bullous erythema pigmentosum (5%). They appear in elderly patients on average 7 days after vaccination and constitute 0.04% of postvaccination reactions.⁷²

• Chilblainlike lesions: several such cases have been reported so far⁷³; they constitute 0.03% of postvaccination reactions.⁷⁰ Clinically, they are similar to those associated with natural COVID-19; they appear mostly after the first dose (64%), on average 5 days after vaccination with the mRNA or adenovirus vaccine, and show a female predominance. The appearance of these lesions in vaccinated patients, who are a priori not carriers of the virus, strongly suggests that CBLLs are due to the immune reaction against SARS-CoV-2 rather than to a direct effect of this virus on the skin, which also is a likely scenario with regards to other skin manifestations seen during the successive COVID-19 epidemic waves.^73-75

• Reactions to hyaluronic acid–containing cosmetic fillers: erythema, edema, and potentially painful induration at the filler injection sites. They constitute 0.04% of postvaccination skin reactions and appear 24 hours after vaccination with mRNA-based vaccines, equally after the first or second dose.⁷⁶

• Pityriasis rosea–like rash: most occur after the second dose of mRNA-based vaccines (0.023% of postvaccination skin reactions).⁷⁰

• Severe reactions: these include acute generalized exanthematous pustulosis⁷⁷ and Stevens-Johnson syndrome.⁷⁸ One case of each has been reported after the adenoviral vector vaccine 3 days after vaccination.

Other more rarely observed manifestations include reactivation/aggravation or de novo appearance of inflammatory dermatoses such as psoriasis,^79,80 leukocytoclastic vasculitis,^81,82 lymphocytic⁸³ or urticarial⁸⁴ vasculitis, Sweet syndrome,⁸⁵ lupus erythematosus, dermatomyositis,^86,87 alopecia,^37,88 infection with Trichophyton rubrum,⁸⁹ Grover disease,⁹⁰ and lymphomatoid reactions (such as recurrences of cutaneous T-cell lymphomas [CD30⁺], and de novo development of lymphomatoid papulosis).⁹¹

FINAL THOUGHTS

COVID-19 is associated with several skin manifestations, even though the causative role of SARS-CoV-2 has remained elusive. These dermatoses are highly polymorphous, mostly benign, and usually spontaneously regressive, but some of them reflect severe infection. They mostly were described during the first pandemic waves, reported in several national and international registries, which allowed for their morphological classification. Currently, cutaneous adverse effects of vaccines are the most frequently reported dermatoses associated with SARS-CoV-2, and it is likely that they will continue to be observed while COVID-19 vaccination lasts. Hopefully the end of the COVID-19 pandemic is near. In January 2023, the International Health Regulations Emergency Committee of the World Health Organization acknowledged that the COVID-19 pandemic may be approaching an inflexion point, and even though the event continues to constitute a public health emergency of international concern, the higher levels of population immunity achieved globally through infection and/or vaccination may limit the impact of SARS-CoV-2 on morbidity and mortality. However, there is little doubt that this virus will remain a permanently established pathogen in humans and animals for the foreseeable future.⁹² Therefore, physicians—especially dermatologists—should be aware of the various skin manifestations associated with COVID-19 so they can more efficiently manage their patients.

COVID-19 is a potentially severe systemic disease caused by SARS-CoV-2. SARS-CoV and Middle East respiratory syndrome (MERS-CoV) caused fatal epidemics in Asia in 2002 to 2003 and in the Arabian Peninsula in 2012, respectively. In 2019, SARS-CoV-2 was detected in patients with severe, sometimes fatal pneumonia of previously unknown origin; it rapidly spread around the world, and the World Health Organization declared the disease a pandemic on March 11, 2020. SARS-CoV-2 is a β-coronavirus that is genetically related to the bat coronavirus and SARS-CoV; it is a single-stranded RNA virus of which several variants and subvariants exist. The SARS-CoV-2 viral particles bind via their surface spike protein (S protein) to the angiotensin-converting enzyme 2 receptor present on the membrane of several cell types, including epidermal and adnexal keratinocytes.^1,2 The α and δ variants, predominant from 2020 to 2021, mainly affected the lower respiratory tract and caused severe, potentially fatal pneumonia, especially in patients older than 65 years and/or with comorbidities, such as obesity, hypertension, diabetes, and (iatrogenic) immunosuppression. The ο variant, which appeared in late 2021, is more contagious than the initial variants, but it causes a less severe disease preferentially affecting the upper respiratory airways.³ As of April 5, 2023, more than 762,000,000 confirmed cases of COVID-19 have been recorded worldwide, causing more than 6,800,000 deaths.⁴

Early studies from China describing the symptoms of COVID-19 reported a low frequency of skin manifestations (0.2%), probably because they were focused on the most severe disease symptoms.⁵ Subsequently, when COVID-19 spread to the rest of the world, an increasing number of skin manifestations were reported in association with the disease. After the first publication from northern Italy in spring 2020, which was specifically devoted to skin manifestations of COVID-19,⁶ an explosive number of publications reported a large number of skin manifestations, and national registries were established in several countries to record these manifestations, such as the American Academy of Dermatology and the International League of Dermatological Societies registry,^7,8 the COVIDSKIN registry of the French Dermatology Society,⁹ and the Italian registry.¹⁰ Highlighting the unprecedented number of scientific articles published on this new disease, a PubMed search of articles indexed for MEDLINE search using the terms SARS-CoV-2 or COVID-19, on April 6, 2023, revealed 351,596 articles; that is more than 300 articles published every day in this database alone, with a large number of them concerning the skin.

SKIN DISEASSES ASSOCIATED WITH COVID-19

There are several types of COVID-19–related skin manifestations, depending on the circumstances of onset and the evolution of the pandemic.

Skin Manifestations Associated With SARS-CoV-2 Infection

The estimated incidence varies greatly according to the published series of patients, possibly depending on the geographic location. The estimated incidence seems lower in Asian countries, such as China (0.2%)⁵ and Japan (0.56%),¹¹ compared with Europe (up to 20%).⁶ Skin manifestations associated with SARS-CoV-2 infection affect individuals of all ages, slightly more females, and are clinically polymorphous; some of them are associated with the severity of the infection.¹² They may precede, accompany, or appear after the symptoms of COVID-19, most often within a month of the infection, of which they rarely are the only manifestation; however, their precise relationship to SARS-CoV-2 is not always well known. They have been classified according to their clinical presentation into several forms.^13-15

Morbilliform Maculopapular Eruption—Representing 16% to 53% of skin manifestations, morbilliform and maculopapular eruptions usually appear within 15 days of infection; they manifest with more or less confluent erythematous macules that may be hemorrhagic/petechial, and usually are asymptomatic and rarely pruritic. The rash mainly affects the trunk and limbs, sparing the face, palmoplantar regions, and mucous membranes; it appears concomitantly with or a few days after the first symptoms of COVID-19 (eg, fever, respiratory symptoms), regresses within a few days, and does not appear to be associated with disease severity. The distinction from maculopapular drug eruptions may be subtle. Histologically, the rash manifests with a spongiform dermatitis (ie, variable parakeratosis; spongiosis; and a mixed dermal perivascular infiltrate of lymphocytes, eosinophils and histiocytes, depending on the lesion age)(Figure 1). The etiopathogenesis is unknown; it may involve immune complexes to SARS-CoV-2 deposited on skin vessels. Treatment is not mandatory; if necessary, local or systemic corticosteroids may be used.

Vesicular (Pseudovaricella) Rash—This rash accounts for 11% to 18% of all skin manifestations and usually appears within 15 days of COVID-19 onset. It manifests with small monomorphous or varicellalike (pseudopolymorphic) vesicles appearing on the trunk, usually in young patients. The vesicles may be herpetiform, hemorrhagic, or pruritic, and appear before or within 3 days of the onset of mild COVID-19 symptoms; they regress within a few days without scarring. Histologically, the lesions show basal cell vacuolization; multinucleated, dyskeratotic/apoptotic or ballooning/acantholytic epidermal keratinocytes; reticular degeneration of the epidermis; intraepidermal vesicles sometimes resembling herpetic vesicular infections or Grover disease; and mild dermal inflammation. There is no specific treatment.

Urticaria—Urticarial rash, or urticaria, represents 5% to 16% of skin manifestations; usually appears within 15 days of disease onset; and manifests with pruritic, migratory, edematous papules appearing mainly on the trunk and occasionally the face and limbs. The urticarial rash tends to be associated with more severe forms of the disease and regresses within a week, responding to antihistamines. Of note, clinically similar rashes can be caused by drugs. Histologically, the lesions show dermal edema and a mild perivascular lymphocytic infiltrate, sometimes admixed with eosinophils.

Chilblainlike Lesions—Chilblainlike lesions (CBLLs) account for 19% of skin manifestations associated with COVID-19¹³ and present as erythematous-purplish, edematous lesions that can be mildly pruritic or painful, appearing on the toes—COVID toes—and more rarely the fingers (Figure 2). They were seen epidemically during the first pandemic wave (2020 lockdown) in several countries, and clinically are very similar to, if not indistinguishable from, idiopathic chilblains, but are not necessarily associated with cold exposure. They appear in young, generally healthy patients or those with mild COVID-19 symptoms 2 to 4 weeks after symptom onset. They regress spontaneously or under local corticosteroid treatment within a few days or weeks. Histologically, CBLLs are indistinguishable from chilblains of other origins, namely idiopathic (seasonal) ones. They manifest with necrosis of epidermal keratinocytes; dermal edema that may be severe, leading to the development of subepidermal pseudobullae; a rather dense perivascular and perieccrine gland lymphocytic infiltrate; and sometimes with vascular lesions (eg, edema of endothelial cells, microthromboses of dermal capillaries and venules, fibrinoid deposits within the wall of dermal venules)(Figure 3).^16-18 Most patients (>80%) with CBLLs have negative serologic or polymerase chain reaction tests for SARS-CoV-2,¹⁹ which generated a lively debate about the role of SARS-CoV-2 in the genesis of CBLLs. According to some authors, SARS-CoV-2 plays no direct role, and CBLLs would occur in young people who sit or walk barefoot on cold floors at home during confinement.^20-23 Remarkably, CBLLs appeared in patients with no history of chilblains during a season that was not particularly cold, namely in France or in southern California, where their incidence was much higher compared to the same time period of prior years. Some reports have supported a direct role for the virus based on questionable observations of the virus within skin lesions (eg, sweat glands, endothelial cells) by immunohistochemistry, electron microscopy, and/or in situ hybridization.^17,24,25 A more satisfactory hypothesis would involve the role of a strong innate immunity leading to elimination of the virus before the development of specific antibodies via the increased production of type 1 interferon (IFN-1); this would affect the vessels, causing CBLLs. This mechanism would be similar to the one observed in some interferonopathies (eg, Aicardi-Goutières syndrome), also characterized by IFN-1 hypersecretion and chilblains.^26-29 According to this hypothesis, CBLLs should be considered a paraviral rash similar to other skin manifestations associated with COVID-19.³⁰

Acro-ischemia—Acro-ischemia livedoid lesions account for 1% to 6% of skin manifestations and comprise lesions of livedo (either reticulated or racemosa); necrotic acral bullae; and gangrenous necrosis of the extremities, especially the toes. The livedoid lesions most often appear within 15 days of COVID-19 symptom onset, and the purpuric lesions somewhat later (2–4 weeks); they mainly affect adult patients, last about 10 days, and are the hallmark of severe infection, presumably related to microthromboses of the cutaneous capillaries (endothelial dysfunction, prothrombotic state, elevated D-dimers). Histologically, they show capillary thrombosis and dermoepidermal necrosis (Figure 4).

Other Reported Polymorphic or Atypical Rashes—Erythema multiforme–like eruptions may appear before other COVID-19 symptoms and manifest as reddish-purple, nearly symmetric, diffuse, occasionally targetoid bullous or necrotic macules. The eruptions mainly affect adults and most often are seen on the palms, elbows, knees, and sometimes the mucous membranes. The rash regresses in 1 to 3 weeks without scarring and represents a delayed cutaneous hypersensitivity reaction. Histologically, the lesions show vacuolization of basal epidermal keratinocytes, keratinocyte necrosis, dermoepidermal detachment, a variably dense dermal T-lymphocytic infiltrate, and red blood cell extravasation (Figure 5).

Leukocytoclastic vasculitis may be generalized or localized. It manifests clinically by petechial/purpuric maculopapules, especially on the legs, mainly in elderly patients with COVID-19. Histologically, the lesions show necrotizing changes of dermal postcapillary venules, neutrophilic perivascular inflammation, red blood cell extravasation, and occasionally vascular IgA deposits by direct immunofluorescence examination. The course usually is benign.

The incidence of pityriasis rosea and of clinically similar rashes (referred to as “pityriasis rosea–like”) increased 5-fold during the COVID-19 pandemic.^31,32 These dermatoses manifest with erythematous, scaly, circinate plaques, typically with an initial herald lesion followed a few days later by smaller erythematous macules. Histologically, the lesions comprise a spongiform dermatitis with intraepidermal exocytosis of red blood cells and a mild to moderate dermal lymphocytic infiltrate.

Erythrodysesthesia, or hand-foot syndrome, manifests with edematous erythema and palmoplantar desquamation accompanied by a burning sensation or pain. This syndrome is known as an adverse effect of some chemotherapies because of the associated drug toxicity and sweat gland inflammation; it was observed in 40% of 666 COVID-19–positive patients with mild to moderate pneumonitis.³³

“COVID nose” is a rare cutaneous manifestation characterized by nasal pigmentation comprising multiple coalescent frecklelike macules on the tip and wings of the nose and sometimes the malar areas. These lesions predominantly appear in women aged 25 to 65 years and show on average 23 days after onset of COVID-19, which is usually mild. This pigmentation is similar to pigmentary changes after infection with chikungunya; it can be treated with depigmenting products such as azelaic acid and hydroquinone cream with sunscreen use, and it regresses in 2 to 4 months.³⁴

Telogen effluvium (excessive and temporary shedding of normal telogen club hairs of the entire scalp due to the disturbance of the hair cycle) is reportedly frequent in patients (48%) 1 month after COVID-19 infection, but it may appear later (after 12 weeks).³⁵ Alopecia also is frequently reported during long (or postacute) COVID-19 (ie, the symptomatic disease phase past the acute 4 weeks’ stage of the infection) and shows a female predominance³⁶; it likely represents the telogen effluvium seen 90 days after a severe illness. Trichodynia (pruritus, burning, pain, or paresthesia of the scalp) also is reportedly common (developing in more than 58% of patients) and is associated with telogen effluvium in 44% of cases. Several cases of alopecia areata (AA) triggered or aggravated by COVID-19 also have been reported^37,38; they could be explained by the “cytokine storm” triggered by the infection, involving T and B lymphocytes; plasmacytoid dendritic cells; natural killer cells with oversecretion of IL-6, IL-4, tumor necrosis factor α, and IFN type I; and a cytotoxic reaction associated with loss of the immune privilege of hair follicles.

Nail Manifestations

The red half-moon nail sign is an asymptomatic purplish-red band around the distal margin of the lunula that affects some adult patients with COVID-19.³⁹ It appears shortly after onset of symptoms, likely the manifestation of vascular inflammation in the nail bed, and regresses slowly after approximately 1 week.⁴⁰ Beau lines are transverse grooves in the nail plate due to the temporary arrest of the proximal nail matrix growth accompanying systemic illnesses; they appear approximately 2 to 3 weeks after the onset of COVID-19.⁴¹ Furthermore, nail alterations can be caused by drugs used to treat COVID-19, such as longitudinal melanonychia due to treatment with hydroxychloroquine or fluorescence of the lunula or nail plate due to treatment with favipiravir.⁴²

Multisystem Inflammatory Syndrome

Multisystem inflammatory syndrome (MIS) is clinically similar to Kawasaki disease; it typically affects children⁴³ and more rarely adults with COVID-19. It manifests with fever, weakness, and biological inflammation and also frequently with skin lesions (72%), which are polymorphous and include morbilliform rash (27%); urticaria (24%); periorbital edema (24%); nonspecific erythema (21.2%); retiform purpura (18%); targetoid lesions (15%); malar rash (15.2%); and periareolar erythema (6%).⁴⁴ Compared to Kawasaki disease, MIS affects slightly older children (mean age, 8.5 vs 3 years) and more frequently includes cardiac and gastrointestinal manifestations; the mortality rate also is slightly higher (2% vs 0.17%).⁴⁵

Confirmed COVID-19 Infection

At the beginning of the pandemic, skin manifestations were reported in patients who were suspected of having COVID-19 but did not always have biological confirmation of SARS-CoV-2 infection due to the unavailability of diagnostic tests or the physical impossibility of testing. However, subsequent studies have confirmed that most of these dermatoses were indeed associated with COVID-19 infection.^9,46 For example, a study of 655 patients with confirmed COVID-19 infection reported maculopapular (38%), vascular (22%), urticarial (15%), and vesicular (15%) rashes; erythema multiforme or Stevens-Johnson–like syndrome (3%, often related to the use of hydroxychloroquine); generalized pruritus (1%); and MIS (0.5%). The study confirmed that CBLLs were mostly seen in young patients with mild disease, whereas livedo (fixed rash) and retiform purpura occurred in older patients with a guarded prognosis.⁴⁶

Remarkably, most dermatoses associated with SARS-CoV-2 infection were reported during the initial waves of the pandemic, which were due to the α and δ viral variants. These manifestations were reported more rarely when the ο variant was predominant, even though most patients (63%) who developed CBLLs in the first wave also developed them during the second pandemic wave.⁴⁷ This decrease in the incidence of COVID-19–associated dermatoses could be because of the lower pathogenicity of the o variant,³ a lower tropism for the skin, and variations in SARS-CoV-2 antigenicity that would induce a different immunologic response, combined with an increasingly stronger herd immunity compared to the first pandemic waves achieved through vaccination and spontaneous infections in the population. Additional reasons may include different baseline characteristics in patients hospitalized with COVID-19 (regarding comorbidities, disease severity, and received treatments), and the possibility that some of the initially reported COVID-19–associated skin manifestations could have been produced by different etiologic agents.⁴⁸ In the last 2 years, COVID-19–related skin manifestations have been reported mainly as adverse events to COVID-19 vaccination.

CUTANEOUS ADVERSE EFFECTS OF DRUGS USED TO TREAT COVID-19

Prior to the advent of vaccines and specific treatments for SARS-CoV-2, various drugs were used—namely hydroxychloroquine, ivermectin, and tocilizumab—that did not prove efficacious and caused diverse adverse effects, including cutaneous eruptions such as urticaria, maculopapular eruptions, erythema multiforme or Stevens-Johnson syndrome, vasculitis, longitudinal melanonychia, and acute generalized exanthematous pustulosis.^49,50 Nirmatrelvir 150 mg–ritonavir 100 mg, which was authorized for emergency use by the US Food and Drug Administration for the treatment of COVID-19, is a viral protease inhibitor blocking the replication of the virus. Ritonavir can induce pruritus, maculopapular rash, acne, Stevens-Johnson syndrome, and toxic epidermal necrolysis; of note, these effects have been observed following administration of ritonavir for treatment of HIV at higher daily doses and for much longer periods of time compared with treatment of COVID-19 (600–1200 mg vs 200 mg/d, respectively). These cutaneous drug side effects are clinically similar to the manifestations caused either directly or indirectly by SARS-CoV-2 infection; therefore, it may be difficult to differentiate them.

DERMATOSES DUE TO PROTECTIVE DEVICES

Dermatoses due to personal protective equipment such as masks or face shields affected the general population and mostly health care professionals⁵¹; 54.4% of 879 health care professionals in one study reported such events.⁵² These dermatoses mainly include contact dermatitis of the face (nose, forehead, and cheeks) of irritant or allergic nature (eg, from preservatives releasing formaldehyde contained in masks and protective goggles). They manifest with skin dryness; desquamation; maceration; fissures; or erosions or ulcerations of the cheeks, forehead, and nose. Cases of pressure urticaria also have been reported. Irritant dermatitis induced by the frequent use of disinfectants (eg, soaps, hydroalcoholic sanitizing gels) also can affect the hands. Allergic hand dermatitis can be caused by medical gloves.

The term maskne (or mask acne) refers to a variety of mechanical acne due to the prolonged use of surgical masks (>4 hours per day for ≥6 weeks); it includes cases of de novo acne and cases of pre-existing acne aggravated by wearing a mask. Maskne is characterized by acne lesions located on the facial area covered by the mask (Figure 6). It is caused by follicular occlusion; increased sebum secretion; mechanical stress (pressure, friction); and dysbiosis of the microbiome induced by changes in heat, pH, and humidity. Preventive measures include application of noncomedogenic moisturizers or gauze before wearing the mask as well as facial cleansing with appropriate nonalcoholic products. Similar to acne, rosacea often is aggravated by prolonged wearing of surgical masks (mask rosacea).^53,54

DERMATOSES REVEALED OR AGGRAVATED BY COVID-19

Exacerbation of various skin diseases has been reported after infection with SARS-CoV-2.⁵⁵ Psoriasis and acrodermatitis continua of Hallopeau,⁵⁶ which may progress into generalized, pustular, or erythrodermic forms,⁵⁷ have been reported; the role of hydroxychloroquine and oral corticosteroids used for the treatment of COVID-19 has been suspected.⁵⁷ Atopic dermatitis patients—26% to 43%—have experienced worsening of their disease after symptomatic COVID-19 infection.⁵⁸ The incidence of herpesvirus infections, including herpes zoster, increased during the pandemic.⁵⁹ Alopecia areata relapses occurred in 42.5% of 392 patients with preexisting disease within 2 months of COVID-19 onset in one study,⁶⁰ possibly favored by the psychological stress; however, some studies have not confirmed the aggravating role of COVID-19 on alopecia areata.⁶¹ Lupus erythematosus, which may relapse in the form of Rowell syndrome,⁶² and livedoid vasculopathy⁶³ also have been reported following COVID-19 infection.

SKIN MANIFESTATIONS ASSOCIATED WITH COVID-19 VACCINES

In parallel with the rapid spread of COVID-19 vaccination,⁴ an increasing number of skin manifestations has been observed following vaccination; these dermatoses now are more frequently reported than those related to natural SARS-CoV-2 infection.^64-70 Vaccine-induced skin manifestations have a reported incidence of approximately 4% and show a female predominance.⁶⁵ Most of them (79%) have been reported in association with messenger RNA (mRNA)–based vaccines, which have been the most widely used; however, the frequency of side effects would be lower after mRNA vaccines than after inactivated virus-based vaccines. Eighteen percent occurred after the adenoviral vector vaccine, and 3% after the inactivated virus vaccine.⁷⁰ Fifty-nine percent were observed after the first dose. They are clinically polymorphous and generally benign, regressing spontaneously after a few days, and they should not constitute a contraindication to vaccination.Interestingly, many skin manifestations are similar to those associated with natural SARS-CoV-2 infection; however, their frequency and severity does not seem to depend on whether the patients had developed skin reactions during prior SARS-CoV-2 infection. These reactions have been classified into several types:

• Immediate local reactions at the injection site: pain, erythema, or edema represent the vast majority (96%) of reactions to vaccines. They appear within 7 days after vaccination (average, 1 day), slightly more frequently (59%) after the first dose. They concern mostly young patients and are benign, regressing in 2 to 3 days.⁷⁰
 

• Delayed local reactions: characterized by pain or pruritus, erythema, and skin induration mimicking cellulitis (COVID arm) and represent 1.7% of postvaccination reactions. They correspond to a delayed hypersensitivity reaction and appear approximately 7 days after vaccination, most often after the first vaccine dose (75% of cases), which is almost invariably mRNA based.⁷⁰

• Urticarial reactions corresponding to an immediate (type 1) hypersensitivity reaction: constitute 1% of postvaccination reactions, probably due to an allergy to vaccine ingredients. They appear on average 1 day after vaccination, almost always with mRNA vaccines.⁷⁰

• Angioedema: characterized by mucosal or subcutaneous edema and constitutes 0.5% of postvaccination reactions. It is a potentially serious reaction that appears on average 12 hours after vaccination, always with an mRNA-based vaccine.⁷⁰

• Morbilliform rash: represents delayed hypersensitivity reactions (0.1% of postvaccination reactions) that appear mostly after the first dose (72%), on average 3 days after vaccination, always with an mRNA-based vaccine.⁷⁰

• Herpes zoster: usually develops after the first vaccine dose in elderly patients (69% of cases) on average 4 days after vaccination and constitutes 0.1% of postvaccination reactions.⁷¹

• Bullous diseases: mainly bullous pemphigoid (90%) and more rarely pemphigus (5%) or bullous erythema pigmentosum (5%). They appear in elderly patients on average 7 days after vaccination and constitute 0.04% of postvaccination reactions.⁷²

• Chilblainlike lesions: several such cases have been reported so far⁷³; they constitute 0.03% of postvaccination reactions.⁷⁰ Clinically, they are similar to those associated with natural COVID-19; they appear mostly after the first dose (64%), on average 5 days after vaccination with the mRNA or adenovirus vaccine, and show a female predominance. The appearance of these lesions in vaccinated patients, who are a priori not carriers of the virus, strongly suggests that CBLLs are due to the immune reaction against SARS-CoV-2 rather than to a direct effect of this virus on the skin, which also is a likely scenario with regards to other skin manifestations seen during the successive COVID-19 epidemic waves.^73-75

• Reactions to hyaluronic acid–containing cosmetic fillers: erythema, edema, and potentially painful induration at the filler injection sites. They constitute 0.04% of postvaccination skin reactions and appear 24 hours after vaccination with mRNA-based vaccines, equally after the first or second dose.⁷⁶

• Pityriasis rosea–like rash: most occur after the second dose of mRNA-based vaccines (0.023% of postvaccination skin reactions).⁷⁰

• Severe reactions: these include acute generalized exanthematous pustulosis⁷⁷ and Stevens-Johnson syndrome.⁷⁸ One case of each has been reported after the adenoviral vector vaccine 3 days after vaccination.

Other more rarely observed manifestations include reactivation/aggravation or de novo appearance of inflammatory dermatoses such as psoriasis,^79,80 leukocytoclastic vasculitis,^81,82 lymphocytic⁸³ or urticarial⁸⁴ vasculitis, Sweet syndrome,⁸⁵ lupus erythematosus, dermatomyositis,^86,87 alopecia,^37,88 infection with Trichophyton rubrum,⁸⁹ Grover disease,⁹⁰ and lymphomatoid reactions (such as recurrences of cutaneous T-cell lymphomas [CD30⁺], and de novo development of lymphomatoid papulosis).⁹¹

FINAL THOUGHTS

COVID-19 is associated with several skin manifestations, even though the causative role of SARS-CoV-2 has remained elusive. These dermatoses are highly polymorphous, mostly benign, and usually spontaneously regressive, but some of them reflect severe infection. They mostly were described during the first pandemic waves, reported in several national and international registries, which allowed for their morphological classification. Currently, cutaneous adverse effects of vaccines are the most frequently reported dermatoses associated with SARS-CoV-2, and it is likely that they will continue to be observed while COVID-19 vaccination lasts. Hopefully the end of the COVID-19 pandemic is near. In January 2023, the International Health Regulations Emergency Committee of the World Health Organization acknowledged that the COVID-19 pandemic may be approaching an inflexion point, and even though the event continues to constitute a public health emergency of international concern, the higher levels of population immunity achieved globally through infection and/or vaccination may limit the impact of SARS-CoV-2 on morbidity and mortality. However, there is little doubt that this virus will remain a permanently established pathogen in humans and animals for the foreseeable future.⁹² Therefore, physicians—especially dermatologists—should be aware of the various skin manifestations associated with COVID-19 so they can more efficiently manage their patients.

To the Editor:

Hailey-Hailey disease (HHD)(also known as familial benign chronic pemphigus) is an inherited autosomal-dominant condition in the family of chronic bullous diseases. It is characterized by flaccid blisters, erosions, and macerated vegetative plaques with a predilection for intertriginous sites. Lesions often are weeping, painful, pruritic, and malodorous, leading to decreased quality of life for patients. Complications of this chronic disease include an increased risk for secondary infection and malignant transformation to squamous cell carcinoma.¹

Treatment of HHD remains difficult. Topical steroids, oral steroids, and ablative techniques such as dermabrasion and ablative lasers are the most widely reported therapies. OnabotulinumtoxinA has been described as a successful treatment for patients with HHD, including for disease recalcitrant to other therapies.² We describe 2 patients with HHD who responded to treatment with intralesional onabotulinumtoxinA injections with and without adjuvant oral glycopyrrolate.

A 54-year-old woman presented with painful flaccid blisters under the breasts (Figure 1A) and in the axillae and groin of 3 weeks’ duration. Biopsy results from this initial visit were consistent with a diagnosis of HHD. The patient reported that the onset of blisters coincided with episodes of severe hyperhidrosis. Therapy with topical and oral steroids, antifungals, antibiotics, and topical aluminum chloride failed to achieve adequate disease control. After a discussion of the risks and benefits, the patient agreed to treatment with injections of onabotulinumtoxinA. At months 0, 3, and 6, the patient received 50 U of onabotulinumtoxinA under the breasts and in the axillae and the groin, for a total of 250 U each session. Each injection consisted of 2.5 U of onabotulinumtoxinA spaced 1-cm apart. Clinical improvement was noted within 2 weeks of initiating neuromodulator therapy. Follow-up at 9 months demonstrated improvement (Figure 1B); however, complete clearance was not achieved, and the patient required ongoing treatment with onabotulinumtoxinA every 3 months.

A 43-year-old woman presented with erythematous eroded plaques of the antecubital fossae, axillae, and chest (Figure 2A) of 10 years’ duration. A biopsy from an outside provider demonstrated findings consistent with a diagnosis of HHD. Prior therapies included topical and oral steroids. After a discussion of the risks and benefits, the patient was treated with onabotulinumtoxinA injections in combination with oral glycopyrrolate 5 mg daily. She received 30 U of onabotulinumtoxinA to each axilla, 10 U to each antecubital fossa, and 20 U to the central chest. At 1 month follow-up, the patient reported great improvement in lesion burden and active disease (Figure 2B). Nine months after treatment, her HHD was in complete remission with glycopyrrolate alone and she did not require further therapy with onabotulinumtoxinA.

Hailey-Hailey disease has been attributed to mutations of the ATPase secretory pathway Ca2+ transporting 1 gene, ATP2C1, that lead to aberrations in calcium signaling and subsequent impaired adhesion between keratinocytes.² These compromised cell-cell connections are worsened by the presence of humidity, causing further acantholysis. Chemical denervation of the sweat glands with botulinum toxin has been postulated to improve HHD by reducing moisture in vulnerable areas. Our 2 cases add to the existing literature documenting tangible clinical results that correlate with this hypothesis.^3-5

Our second case is unique in that the patient achieved rapid improvement using a combination of onabotulinumtoxinA and glycopyrrolate therapy. Both onabotulinumtoxinA and glycopyrrolate inhibit acetylcholine signaling that is required for sweat production; however, each drug exerts its effect on different zones of the cholinergic pathway, which may partially account for the synergistic effect of onabotulinumtoxinA and glycopyrrolate to improve HHD, as sweating is dually inhibited by the 2 drugs. Additionally, the combined local and systemic administration of these anticholinergic medications may further potentiate the sweat blockade, particularly in areas most prone to disease.

Botulinum toxin for the treatment of HHD is an effective monotherapy. The addition of an oral anticholinergic to local neuromodulator injections may speed symptom resolution and sustain disease remission. Further studies to evaluate this combination are warranted.

To the Editor:

Hailey-Hailey disease (HHD)(also known as familial benign chronic pemphigus) is an inherited autosomal-dominant condition in the family of chronic bullous diseases. It is characterized by flaccid blisters, erosions, and macerated vegetative plaques with a predilection for intertriginous sites. Lesions often are weeping, painful, pruritic, and malodorous, leading to decreased quality of life for patients. Complications of this chronic disease include an increased risk for secondary infection and malignant transformation to squamous cell carcinoma.¹

Treatment of HHD remains difficult. Topical steroids, oral steroids, and ablative techniques such as dermabrasion and ablative lasers are the most widely reported therapies. OnabotulinumtoxinA has been described as a successful treatment for patients with HHD, including for disease recalcitrant to other therapies.² We describe 2 patients with HHD who responded to treatment with intralesional onabotulinumtoxinA injections with and without adjuvant oral glycopyrrolate.

A 54-year-old woman presented with painful flaccid blisters under the breasts (Figure 1A) and in the axillae and groin of 3 weeks’ duration. Biopsy results from this initial visit were consistent with a diagnosis of HHD. The patient reported that the onset of blisters coincided with episodes of severe hyperhidrosis. Therapy with topical and oral steroids, antifungals, antibiotics, and topical aluminum chloride failed to achieve adequate disease control. After a discussion of the risks and benefits, the patient agreed to treatment with injections of onabotulinumtoxinA. At months 0, 3, and 6, the patient received 50 U of onabotulinumtoxinA under the breasts and in the axillae and the groin, for a total of 250 U each session. Each injection consisted of 2.5 U of onabotulinumtoxinA spaced 1-cm apart. Clinical improvement was noted within 2 weeks of initiating neuromodulator therapy. Follow-up at 9 months demonstrated improvement (Figure 1B); however, complete clearance was not achieved, and the patient required ongoing treatment with onabotulinumtoxinA every 3 months.

A 43-year-old woman presented with erythematous eroded plaques of the antecubital fossae, axillae, and chest (Figure 2A) of 10 years’ duration. A biopsy from an outside provider demonstrated findings consistent with a diagnosis of HHD. Prior therapies included topical and oral steroids. After a discussion of the risks and benefits, the patient was treated with onabotulinumtoxinA injections in combination with oral glycopyrrolate 5 mg daily. She received 30 U of onabotulinumtoxinA to each axilla, 10 U to each antecubital fossa, and 20 U to the central chest. At 1 month follow-up, the patient reported great improvement in lesion burden and active disease (Figure 2B). Nine months after treatment, her HHD was in complete remission with glycopyrrolate alone and she did not require further therapy with onabotulinumtoxinA.

Hailey-Hailey disease has been attributed to mutations of the ATPase secretory pathway Ca2+ transporting 1 gene, ATP2C1, that lead to aberrations in calcium signaling and subsequent impaired adhesion between keratinocytes.² These compromised cell-cell connections are worsened by the presence of humidity, causing further acantholysis. Chemical denervation of the sweat glands with botulinum toxin has been postulated to improve HHD by reducing moisture in vulnerable areas. Our 2 cases add to the existing literature documenting tangible clinical results that correlate with this hypothesis.^3-5

Our second case is unique in that the patient achieved rapid improvement using a combination of onabotulinumtoxinA and glycopyrrolate therapy. Both onabotulinumtoxinA and glycopyrrolate inhibit acetylcholine signaling that is required for sweat production; however, each drug exerts its effect on different zones of the cholinergic pathway, which may partially account for the synergistic effect of onabotulinumtoxinA and glycopyrrolate to improve HHD, as sweating is dually inhibited by the 2 drugs. Additionally, the combined local and systemic administration of these anticholinergic medications may further potentiate the sweat blockade, particularly in areas most prone to disease.

Botulinum toxin for the treatment of HHD is an effective monotherapy. The addition of an oral anticholinergic to local neuromodulator injections may speed symptom resolution and sustain disease remission. Further studies to evaluate this combination are warranted.

To the Editor:

Hailey-Hailey disease (HHD)(also known as familial benign chronic pemphigus) is an inherited autosomal-dominant condition in the family of chronic bullous diseases. It is characterized by flaccid blisters, erosions, and macerated vegetative plaques with a predilection for intertriginous sites. Lesions often are weeping, painful, pruritic, and malodorous, leading to decreased quality of life for patients. Complications of this chronic disease include an increased risk for secondary infection and malignant transformation to squamous cell carcinoma.¹

Treatment of HHD remains difficult. Topical steroids, oral steroids, and ablative techniques such as dermabrasion and ablative lasers are the most widely reported therapies. OnabotulinumtoxinA has been described as a successful treatment for patients with HHD, including for disease recalcitrant to other therapies.² We describe 2 patients with HHD who responded to treatment with intralesional onabotulinumtoxinA injections with and without adjuvant oral glycopyrrolate.

A 54-year-old woman presented with painful flaccid blisters under the breasts (Figure 1A) and in the axillae and groin of 3 weeks’ duration. Biopsy results from this initial visit were consistent with a diagnosis of HHD. The patient reported that the onset of blisters coincided with episodes of severe hyperhidrosis. Therapy with topical and oral steroids, antifungals, antibiotics, and topical aluminum chloride failed to achieve adequate disease control. After a discussion of the risks and benefits, the patient agreed to treatment with injections of onabotulinumtoxinA. At months 0, 3, and 6, the patient received 50 U of onabotulinumtoxinA under the breasts and in the axillae and the groin, for a total of 250 U each session. Each injection consisted of 2.5 U of onabotulinumtoxinA spaced 1-cm apart. Clinical improvement was noted within 2 weeks of initiating neuromodulator therapy. Follow-up at 9 months demonstrated improvement (Figure 1B); however, complete clearance was not achieved, and the patient required ongoing treatment with onabotulinumtoxinA every 3 months.

A 43-year-old woman presented with erythematous eroded plaques of the antecubital fossae, axillae, and chest (Figure 2A) of 10 years’ duration. A biopsy from an outside provider demonstrated findings consistent with a diagnosis of HHD. Prior therapies included topical and oral steroids. After a discussion of the risks and benefits, the patient was treated with onabotulinumtoxinA injections in combination with oral glycopyrrolate 5 mg daily. She received 30 U of onabotulinumtoxinA to each axilla, 10 U to each antecubital fossa, and 20 U to the central chest. At 1 month follow-up, the patient reported great improvement in lesion burden and active disease (Figure 2B). Nine months after treatment, her HHD was in complete remission with glycopyrrolate alone and she did not require further therapy with onabotulinumtoxinA.

Hailey-Hailey disease has been attributed to mutations of the ATPase secretory pathway Ca2+ transporting 1 gene, ATP2C1, that lead to aberrations in calcium signaling and subsequent impaired adhesion between keratinocytes.² These compromised cell-cell connections are worsened by the presence of humidity, causing further acantholysis. Chemical denervation of the sweat glands with botulinum toxin has been postulated to improve HHD by reducing moisture in vulnerable areas. Our 2 cases add to the existing literature documenting tangible clinical results that correlate with this hypothesis.^3-5

Our second case is unique in that the patient achieved rapid improvement using a combination of onabotulinumtoxinA and glycopyrrolate therapy. Both onabotulinumtoxinA and glycopyrrolate inhibit acetylcholine signaling that is required for sweat production; however, each drug exerts its effect on different zones of the cholinergic pathway, which may partially account for the synergistic effect of onabotulinumtoxinA and glycopyrrolate to improve HHD, as sweating is dually inhibited by the 2 drugs. Additionally, the combined local and systemic administration of these anticholinergic medications may further potentiate the sweat blockade, particularly in areas most prone to disease.

Botulinum toxin for the treatment of HHD is an effective monotherapy. The addition of an oral anticholinergic to local neuromodulator injections may speed symptom resolution and sustain disease remission. Further studies to evaluate this combination are warranted.

Torrelo and colleagues described the efficacy and safety of baricitinib in combination with topical corticosteroids in pediatric patients with moderate to severe atopic dermatitis. At the high dose of 4 mg daily, the IGA success rate was about 40%, similar to what we expect for adults treated with dupilumab and less than what we might expect with upadacitinib.

Studies have already been done on efficacy and safety of baricitinib in adults with atopic dermatitis. But baricitinib is indicated for the treatment of adult patients with severe alopecia areata and is not currently indicated as a treatment for anyone with atopic dermatitis, at least not in the United States. At this time, I think the most useful aspect of Torrelo and colleagues' findings is being able to tell our adult patients with alopecia areata that baricitinib was safe enough that they could test it in children as young as 2 years old with eczema.

Perälä and colleagues' report comparing topical tacrolimus and topical corticosteroids (1% hydrocortisone acetate or, if needed, 0.1% hydrocortisone butyrate ointment) in young children with atopic dermatitis is fascinating. They saw patients back at 1 week and followed them for 3 years. In just 1 week, both groups had massive and similar improvement in their atopic dermatitis, and that improvement continued throughout the study. Here are some take-home points:

• Atopic dermatitis responds rapidly to low-to-medium–strength topical steroids.
• Bringing patients back at 1 week may have been a critical aspect of this study, as adherence to topicals can be abysmal; bringing patients back at 1 week probably enables them to use their treatment much better than they would otherwise.
• If we need a nonsteroidal topical, we have an excellent one available at low cost in the form of topical tacrolimus.

Perälä and colleagues also did this study to see whether good treatment of atopic dermatitis in these young children would have long-term benefits on atopic airway issues. Because the researchers didn't have a placebo group (and considered it unethical to have one), we cannot tell whether the topical treatment provided any benefit in that regard.

Yamamoto-Hanada and colleaguesexamined whether "enhanced" topical steroid treatment would prevent food allergy in children with eczema compared with standard topical steroid treatment. Perhaps a better word than "enhanced" would be "aggressive." The enhanced treatment entailed having infants receive alclometasone dipropionate for the whole face and betamethasone valerate for the whole body except face and scalp. While the researchers saw a reduction in egg allergy (from roughly 40% to 30%), they also saw reduced body weight and height. A key take-home message is that with extensive use of topical steroids, we can see systemic effects.

Torrelo and colleagues described the efficacy and safety of baricitinib in combination with topical corticosteroids in pediatric patients with moderate to severe atopic dermatitis. At the high dose of 4 mg daily, the IGA success rate was about 40%, similar to what we expect for adults treated with dupilumab and less than what we might expect with upadacitinib.

Studies have already been done on efficacy and safety of baricitinib in adults with atopic dermatitis. But baricitinib is indicated for the treatment of adult patients with severe alopecia areata and is not currently indicated as a treatment for anyone with atopic dermatitis, at least not in the United States. At this time, I think the most useful aspect of Torrelo and colleagues' findings is being able to tell our adult patients with alopecia areata that baricitinib was safe enough that they could test it in children as young as 2 years old with eczema.

Perälä and colleagues' report comparing topical tacrolimus and topical corticosteroids (1% hydrocortisone acetate or, if needed, 0.1% hydrocortisone butyrate ointment) in young children with atopic dermatitis is fascinating. They saw patients back at 1 week and followed them for 3 years. In just 1 week, both groups had massive and similar improvement in their atopic dermatitis, and that improvement continued throughout the study. Here are some take-home points:

• Atopic dermatitis responds rapidly to low-to-medium–strength topical steroids.
• Bringing patients back at 1 week may have been a critical aspect of this study, as adherence to topicals can be abysmal; bringing patients back at 1 week probably enables them to use their treatment much better than they would otherwise.
• If we need a nonsteroidal topical, we have an excellent one available at low cost in the form of topical tacrolimus.

Perälä and colleagues also did this study to see whether good treatment of atopic dermatitis in these young children would have long-term benefits on atopic airway issues. Because the researchers didn't have a placebo group (and considered it unethical to have one), we cannot tell whether the topical treatment provided any benefit in that regard.

Yamamoto-Hanada and colleaguesexamined whether "enhanced" topical steroid treatment would prevent food allergy in children with eczema compared with standard topical steroid treatment. Perhaps a better word than "enhanced" would be "aggressive." The enhanced treatment entailed having infants receive alclometasone dipropionate for the whole face and betamethasone valerate for the whole body except face and scalp. While the researchers saw a reduction in egg allergy (from roughly 40% to 30%), they also saw reduced body weight and height. A key take-home message is that with extensive use of topical steroids, we can see systemic effects.

Torrelo and colleagues described the efficacy and safety of baricitinib in combination with topical corticosteroids in pediatric patients with moderate to severe atopic dermatitis. At the high dose of 4 mg daily, the IGA success rate was about 40%, similar to what we expect for adults treated with dupilumab and less than what we might expect with upadacitinib.

Studies have already been done on efficacy and safety of baricitinib in adults with atopic dermatitis. But baricitinib is indicated for the treatment of adult patients with severe alopecia areata and is not currently indicated as a treatment for anyone with atopic dermatitis, at least not in the United States. At this time, I think the most useful aspect of Torrelo and colleagues' findings is being able to tell our adult patients with alopecia areata that baricitinib was safe enough that they could test it in children as young as 2 years old with eczema.

Perälä and colleagues' report comparing topical tacrolimus and topical corticosteroids (1% hydrocortisone acetate or, if needed, 0.1% hydrocortisone butyrate ointment) in young children with atopic dermatitis is fascinating. They saw patients back at 1 week and followed them for 3 years. In just 1 week, both groups had massive and similar improvement in their atopic dermatitis, and that improvement continued throughout the study. Here are some take-home points:

• Atopic dermatitis responds rapidly to low-to-medium–strength topical steroids.
• Bringing patients back at 1 week may have been a critical aspect of this study, as adherence to topicals can be abysmal; bringing patients back at 1 week probably enables them to use their treatment much better than they would otherwise.
• If we need a nonsteroidal topical, we have an excellent one available at low cost in the form of topical tacrolimus.

Perälä and colleagues also did this study to see whether good treatment of atopic dermatitis in these young children would have long-term benefits on atopic airway issues. Because the researchers didn't have a placebo group (and considered it unethical to have one), we cannot tell whether the topical treatment provided any benefit in that regard.

Yamamoto-Hanada and colleaguesexamined whether "enhanced" topical steroid treatment would prevent food allergy in children with eczema compared with standard topical steroid treatment. Perhaps a better word than "enhanced" would be "aggressive." The enhanced treatment entailed having infants receive alclometasone dipropionate for the whole face and betamethasone valerate for the whole body except face and scalp. While the researchers saw a reduction in egg allergy (from roughly 40% to 30%), they also saw reduced body weight and height. A key take-home message is that with extensive use of topical steroids, we can see systemic effects.

Abdul Moiz Hafiz, MD, was flabbergasted when he received a phone call from his institution’s credentialing office telling him that he was not certified for interventional cardiology – even though he had passed that exam in 2016.

Dr. Hafiz, who directs the Advanced Structural Heart Disease Program at Southern Illinois University, phoned the American Board of Internal Medicine (ABIM), where he learned that to restore his credentials, he would need to pay $1,225 in maintenance of certification (MOC) fees.

Like Dr. Hafiz, many physicians have been dismayed to learn that the ABIM is now listing as “not certified” physicians who have passed board exams but have not paid annual MOC fees of $220 per year for the first certificate and $120 for each additional certificate.

Even doctors who are participating in mandatory continuing education outside the ABIM’s auspices are finding themselves listed as “not certified.” Some physicians learned of the policy change only after applying for hospital privileges or for jobs that require ABIM certification.

Now that increasing numbers of physicians are employed by hospitals and health care organizations that require ABIM certification, many doctors have no option but to pony up the fees if they want to continue to practice medicine.

“We have no say in the matter,” said Dr. Hafiz, “and there’s no appeal process.”

The change affects nearly 330,000 physicians. Responses to the policy on Twitter included accusations of extortion and denunciations of the ABIM’s “money grab policies.”

Sunil Rao, MD, director of interventional cardiology at NYU Langone Health and president of the Society for Cardiovascular Angiography and Interventions (SCAI), has heard from many SCAI members who had experiences similar to Dr. Hafiz’s. While Dr. Rao describes some of the Twitter outrage as “emotional,” he does acknowledge that the ABIM’s moves appear to be financially motivated.

“The issue here was that as soon as they paid the fee, all of a sudden, ABIM flipped the switch and said they were certified,” he said. “It certainly sounds like a purely financial kind of structure.”

Richard Baron, MD, president and CEO of the ABIM, said doctors are misunderstanding the policy change.

“No doctor loses certification solely for failure to pay fees,” Dr. Baron told this news organization. “What caused them to be reported as not certified was that we didn’t have evidence that they had met program requirements. They could say, ‘But I did meet program requirements, you just didn’t know it.’ To which our answer would be, for us to know it, we have to process them. And our policy is that we don’t process them unless you are current on your fees.”

This is not the first time ABIM policies have alienated physicians.

Last year, the ABIM raised its MOC fees from $165 to $220. That also prompted a wave of outrage. Other grievances go further back. At one time, being board certified was a lifetime credential. However, in 1990 the ABIM made periodic recertification mandatory.

The process, which came to be known as “maintenance of certification,” had to be completed every 10 years, and fees were charged for each certification. At that point, said Dr. Baron, the relationship between the ABIM and physicians changed from a one-time interaction to a career-long relationship. He advises doctors to check in periodically on their portal page at the ABIM or download the app so they will always know their status.

Many physicians would prefer not to be bound to a lifetime relationship with the ABIM. There is an alternative licensing board, the National Board of Physicians and Surgeons (NBPAS), but it is accepted by only a limited number of hospitals.

“Until the NBPAS gains wide recognition,” said Dr. Hafiz, “the ABIM is going to continue to have basically a monopoly over the market.”

The value of MOC itself has been called into question. “There are no direct data supporting the value of the MOC process in either improving care, making patient care safer, or making patient care higher quality,” said Dr. Rao. This feeds frustration in a clinical community already dealing with onerous training requirements and expensive board certification exams and adds to the perception that it is a purely financial transaction, he said. (Studies examining whether the MOC system improves patient care have shown mixed results.)

The true value of the ABIM to physicians, Dr. Baron contends, is that the organization is an independent third party that differentiates those doctors from people who don’t have their skills, training, and expertise. “In these days, where anyone can be an ‘expert’ on the Internet, that’s more valuable than ever before,” he said.
 

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

Abdul Moiz Hafiz, MD, was flabbergasted when he received a phone call from his institution’s credentialing office telling him that he was not certified for interventional cardiology – even though he had passed that exam in 2016.

Dr. Hafiz, who directs the Advanced Structural Heart Disease Program at Southern Illinois University, phoned the American Board of Internal Medicine (ABIM), where he learned that to restore his credentials, he would need to pay $1,225 in maintenance of certification (MOC) fees.

Like Dr. Hafiz, many physicians have been dismayed to learn that the ABIM is now listing as “not certified” physicians who have passed board exams but have not paid annual MOC fees of $220 per year for the first certificate and $120 for each additional certificate.

Even doctors who are participating in mandatory continuing education outside the ABIM’s auspices are finding themselves listed as “not certified.” Some physicians learned of the policy change only after applying for hospital privileges or for jobs that require ABIM certification.

Now that increasing numbers of physicians are employed by hospitals and health care organizations that require ABIM certification, many doctors have no option but to pony up the fees if they want to continue to practice medicine.

“We have no say in the matter,” said Dr. Hafiz, “and there’s no appeal process.”

The change affects nearly 330,000 physicians. Responses to the policy on Twitter included accusations of extortion and denunciations of the ABIM’s “money grab policies.”

Sunil Rao, MD, director of interventional cardiology at NYU Langone Health and president of the Society for Cardiovascular Angiography and Interventions (SCAI), has heard from many SCAI members who had experiences similar to Dr. Hafiz’s. While Dr. Rao describes some of the Twitter outrage as “emotional,” he does acknowledge that the ABIM’s moves appear to be financially motivated.

“The issue here was that as soon as they paid the fee, all of a sudden, ABIM flipped the switch and said they were certified,” he said. “It certainly sounds like a purely financial kind of structure.”

Richard Baron, MD, president and CEO of the ABIM, said doctors are misunderstanding the policy change.

“No doctor loses certification solely for failure to pay fees,” Dr. Baron told this news organization. “What caused them to be reported as not certified was that we didn’t have evidence that they had met program requirements. They could say, ‘But I did meet program requirements, you just didn’t know it.’ To which our answer would be, for us to know it, we have to process them. And our policy is that we don’t process them unless you are current on your fees.”

This is not the first time ABIM policies have alienated physicians.

Last year, the ABIM raised its MOC fees from $165 to $220. That also prompted a wave of outrage. Other grievances go further back. At one time, being board certified was a lifetime credential. However, in 1990 the ABIM made periodic recertification mandatory.

The process, which came to be known as “maintenance of certification,” had to be completed every 10 years, and fees were charged for each certification. At that point, said Dr. Baron, the relationship between the ABIM and physicians changed from a one-time interaction to a career-long relationship. He advises doctors to check in periodically on their portal page at the ABIM or download the app so they will always know their status.

Many physicians would prefer not to be bound to a lifetime relationship with the ABIM. There is an alternative licensing board, the National Board of Physicians and Surgeons (NBPAS), but it is accepted by only a limited number of hospitals.

“Until the NBPAS gains wide recognition,” said Dr. Hafiz, “the ABIM is going to continue to have basically a monopoly over the market.”

The value of MOC itself has been called into question. “There are no direct data supporting the value of the MOC process in either improving care, making patient care safer, or making patient care higher quality,” said Dr. Rao. This feeds frustration in a clinical community already dealing with onerous training requirements and expensive board certification exams and adds to the perception that it is a purely financial transaction, he said. (Studies examining whether the MOC system improves patient care have shown mixed results.)

The true value of the ABIM to physicians, Dr. Baron contends, is that the organization is an independent third party that differentiates those doctors from people who don’t have their skills, training, and expertise. “In these days, where anyone can be an ‘expert’ on the Internet, that’s more valuable than ever before,” he said.
 

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

Abdul Moiz Hafiz, MD, was flabbergasted when he received a phone call from his institution’s credentialing office telling him that he was not certified for interventional cardiology – even though he had passed that exam in 2016.

Dr. Hafiz, who directs the Advanced Structural Heart Disease Program at Southern Illinois University, phoned the American Board of Internal Medicine (ABIM), where he learned that to restore his credentials, he would need to pay $1,225 in maintenance of certification (MOC) fees.

Like Dr. Hafiz, many physicians have been dismayed to learn that the ABIM is now listing as “not certified” physicians who have passed board exams but have not paid annual MOC fees of $220 per year for the first certificate and $120 for each additional certificate.

Even doctors who are participating in mandatory continuing education outside the ABIM’s auspices are finding themselves listed as “not certified.” Some physicians learned of the policy change only after applying for hospital privileges or for jobs that require ABIM certification.

Now that increasing numbers of physicians are employed by hospitals and health care organizations that require ABIM certification, many doctors have no option but to pony up the fees if they want to continue to practice medicine.

“We have no say in the matter,” said Dr. Hafiz, “and there’s no appeal process.”

The change affects nearly 330,000 physicians. Responses to the policy on Twitter included accusations of extortion and denunciations of the ABIM’s “money grab policies.”

Sunil Rao, MD, director of interventional cardiology at NYU Langone Health and president of the Society for Cardiovascular Angiography and Interventions (SCAI), has heard from many SCAI members who had experiences similar to Dr. Hafiz’s. While Dr. Rao describes some of the Twitter outrage as “emotional,” he does acknowledge that the ABIM’s moves appear to be financially motivated.

“The issue here was that as soon as they paid the fee, all of a sudden, ABIM flipped the switch and said they were certified,” he said. “It certainly sounds like a purely financial kind of structure.”

Richard Baron, MD, president and CEO of the ABIM, said doctors are misunderstanding the policy change.

“No doctor loses certification solely for failure to pay fees,” Dr. Baron told this news organization. “What caused them to be reported as not certified was that we didn’t have evidence that they had met program requirements. They could say, ‘But I did meet program requirements, you just didn’t know it.’ To which our answer would be, for us to know it, we have to process them. And our policy is that we don’t process them unless you are current on your fees.”

This is not the first time ABIM policies have alienated physicians.

Last year, the ABIM raised its MOC fees from $165 to $220. That also prompted a wave of outrage. Other grievances go further back. At one time, being board certified was a lifetime credential. However, in 1990 the ABIM made periodic recertification mandatory.

The process, which came to be known as “maintenance of certification,” had to be completed every 10 years, and fees were charged for each certification. At that point, said Dr. Baron, the relationship between the ABIM and physicians changed from a one-time interaction to a career-long relationship. He advises doctors to check in periodically on their portal page at the ABIM or download the app so they will always know their status.

Many physicians would prefer not to be bound to a lifetime relationship with the ABIM. There is an alternative licensing board, the National Board of Physicians and Surgeons (NBPAS), but it is accepted by only a limited number of hospitals.

“Until the NBPAS gains wide recognition,” said Dr. Hafiz, “the ABIM is going to continue to have basically a monopoly over the market.”

The value of MOC itself has been called into question. “There are no direct data supporting the value of the MOC process in either improving care, making patient care safer, or making patient care higher quality,” said Dr. Rao. This feeds frustration in a clinical community already dealing with onerous training requirements and expensive board certification exams and adds to the perception that it is a purely financial transaction, he said. (Studies examining whether the MOC system improves patient care have shown mixed results.)

The true value of the ABIM to physicians, Dr. Baron contends, is that the organization is an independent third party that differentiates those doctors from people who don’t have their skills, training, and expertise. “In these days, where anyone can be an ‘expert’ on the Internet, that’s more valuable than ever before,” he said.
 

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

“BMI is trash. Full stop.” This controversial tweet, which received thousands of likes and retweets, was cited in a recent article by one doctor on when physicians might stop using body mass index (BMI) to diagnose obesity.

BMI has for years been the consensus default method for assessing whether a person is overweight or has obesity, and is still widely used as the gatekeeper metric for treatment eligibility for certain weight-loss agents and bariatric surgery.

But growing appreciation of the limitations of BMI is causing many clinicians to consider alternative measures of obesity that can better assess both the amount of adiposity as well as its body location, an important determinant of the cardiometabolic consequences of fat.

Alternative metrics include waist circumference and/or waist-to-height ratio (WHtR); imaging methods such as CT, MRI, and dual-energy x-ray absorptiometry (DXA); and bioelectrical impedance to assess fat volume and location. All have made some inroads on the tight grip BMI has had on obesity assessment.

Chances are, however, that BMI will not fade away anytime soon given how entrenched it has become in clinical practice and for insurance coverage, as well as its relative simplicity and precision.

“BMI is embedded in a wide range of guidelines on the use of medications and surgery. It’s embedded in Food and Drug Administration regulations and for billing and insurance coverage. It would take extremely strong data and years of work to undo the infrastructure built around BMI and replace it with something else. I don’t see that happening [anytime soon],” commented Daniel H. Bessesen, MD, a professor at the University of Colorado at Denver, Aurora, and chief of endocrinology for Denver Health.

“It would be almost impossible to replace all the studies that have used BMI with investigations using some other measure,” he said.
 

BMI Is ‘imperfect’

The entrenched position of BMI as the go-to metric doesn’t keep detractors from weighing in. As noted in a commentary on current clinical challenges surrounding obesity recently published in Annals of Internal Medicine, the journal’s editor-in-chief, Christine Laine, MD, and senior deputy editor Christina C. Wee, MD, listed six top issues clinicians must deal with, one of which, they say, is the need for a better measure of obesity than BMI.

“Unfortunately, BMI is an imperfect measure of body composition that differs with ethnicity, sex, body frame, and muscle mass,” noted Dr. Laine and Dr. Wee.

BMI is based on a person’s weight in kilograms divided by the square of their height in meters. A “healthy” BMI is between 18.5 and 24.9 kg/m2, overweight is 25-29.9, and 30 or greater is considered to represent obesity. However, certain ethnic groups have lower cutoffs for overweight or obesity because of evidence that such individuals can be at higher risk of obesity-related comorbidities at lower BMIs.

“BMI was chosen as the initial screening tool [for obesity] not because anyone thought it was perfect or the best measure but because of its simplicity. All you need is height, weight, and a calculator,” Dr. Wee said in an interview.

Numerous online calculators are available, including one from the Centers for Disease Control and Prevention where height in feet and inches and weight in pounds can be entered to generate the BMI.

BMI is also inherently limited by being “a proxy for adiposity” and not a direct measure, added Dr. Wee, who is also director of the Obesity Research Program of Beth Israel Deaconess Medical Center, Boston.

As such, BMI can’t distinguish between fat and muscle because it relies on weight only to gauge adiposity, noted Tiffany Powell-Wiley, MD, an obesity researcher at the National Heart, Lung, and Blood Institute in Bethesda, Md. Another shortcoming of BMI is that it “is good for distinguishing population-level risk for cardiovascular disease and other chronic diseases, but it does not help as much for distinguishing risk at an individual level,” she said in an interview.

These and other drawbacks have prompted researchers to look for other useful metrics. WHtR, for example, has recently made headway as a potential BMI alternative or complement.
 

The case for WHtR

Concern about overreliance on BMI despite its limitations is not new. In 2015, an American Heart Association scientific statement from the group’s Obesity Committee concluded that “BMI alone, even with lower thresholds, is a useful but not an ideal tool for identification of obesity or assessment of cardiovascular risk,” especially for people from Asian, Black, Hispanic, and Pacific Islander populations.

The writing panel also recommended that clinicians measure waist circumference annually and use that information along with BMI “to better gauge cardiovascular risk in diverse populations.”

Momentum for moving beyond BMI alone has continued to build following the AHA statement.

In September 2022, the National Institute for Health and Care Excellence, which sets policies for the United Kingdom’s National Health Service, revised its guidancefor assessment and management of people with obesity. The updated guidance recommends that when clinicians assess “adults with BMI below 35 kg/m2, measure and use their WHtR, as well as their BMI, as a practical estimate of central adiposity and use these measurements to help to assess and predict health risks.”

NICE released an extensive literature review with the revision, and based on the evidence, said that “using waist-to-height ratio as well as BMI would help give a practical estimate of central adiposity in adults with BMI under 35 kg/m². This would in turn help professionals assess and predict health risks.”

However, the review added that, “because people with a BMI over 35 kg/m² are always likely to have a high WHtR, the committee recognized that it may not be a useful addition for predicting health risks in this group.” The 2022 NICE review also said that it is “important to estimate central adiposity when assessing future health risks, including for people whose BMI is in the healthy-weight category.”

This new emphasis by NICE on measuring and using WHtR as part of obesity assessment “represents an important change in population health policy,” commented Dr. Powell-Wiley. “I expect more professional organizations will endorse use of waist circumference or waist-to-height ratio now that NICE has taken this step,” she predicted.

Waist circumference and WHtR may become standard measures of adiposity in clinical practice over the next 5-10 years.

The recent move by NICE to highlight a complementary role for WHtR “is another acknowledgment that BMI is an imperfect tool for stratifying cardiometabolic risk in a diverse population, especially in people with lower BMIs” because of its variability, commented Jamie Almandoz, MD, medical director of the weight wellness program at UT Southwestern Medical Center, Dallas.
 

WHtR vs. BMI

Another recent step forward for WHtR came with the publication of a post hoc analysis of data collected in the PARADIGM-HF trial, a study that had the primary purpose of comparing two medications for improving outcomes in more than 8,000 patients with heart failure with reduced ejection fraction.

The new analysis showed that “two indices that incorporate waist circumference and height, but not weight, showed a clearer association between greater adiposity and a higher risk of heart failure hospitalization,” compared with BMI.

WHtR was one of the two indices identified as being a better correlate for the adverse effect of excess adiposity compared with BMI.

The authors of the post hoc analysis did not design their analysis to compare WHtR with BMI. Instead, their goal was to better understand what’s known as the “obesity paradox” in people with heart failure with reduced ejection fraction: The recurring observation that, when these patients with heart failure have lower BMIs they fare worse, with higher rates of mortality and adverse cardiovascular outcomes, compared with patients with higher BMIs.

The new analysis showed that this paradox disappeared when WHtR was substituted for BMI as the obesity metric.

This “provides meaningful data about the superiority of WHtR, compared with BMI, for predicting heart failure outcomes,” said Dr. Powell-Wiley, although she cautioned that the analysis was limited by scant data in diverse populations and did not look at other important cardiovascular disease outcomes. While Dr. Powell-Wiley does not think that WHtR needs assessment in a prospective, controlled trial, she called for analysis of pooled prospective studies with more diverse populations to better document the advantages of WHtR over BMI.

The PARADIGM-HF post hoc analysis shows again how flawed BMI is for health assessment and the relative importance of an individualized understanding of a person’s body composition, Dr. Almandoz said in an interview. “As we collect more data, there is increasing awareness of how imperfect BMI is.”
 

Measuring waist circumference is tricky

Although WHtR looks promising as a substitute for or add-on to BMI, it has its own limitations, particularly the challenge of accurately measuring waist circumference.

Measuring waist circumference “not only takes more time but requires the assessor to be well trained about where to put the tape measure and making sure it’s measured at the same place each time,” even when different people take serial measurements from individual patients, noted Dr. Wee. Determining waist circumference can also be technically difficult when done on larger people, she added, and collectively these challenges make waist circumference “less reproducible from measurement to measurement.”

“It’s relatively clear how to standardize measurement of weight and height, but there is a huge amount of variability when the waist is measured,” agreed Dr. Almandoz. “And waist circumference also differs by ethnicity, race, sex, and body frame. There are significant differences in waist circumference levels that associate with increased health risks” between, for example, White and South Asian people.

Another limitation of waist circumference and WHtR is that they “cannot differentiate between visceral and abdominal subcutaneous adipose tissue, which are vastly different regarding cardiometabolic risk, commented Ian Neeland, MD, director of cardiovascular prevention at the University Hospitals Harrington Heart & Vascular Institute, Cleveland.
 

The imaging option

“Waist-to-height ratio is not the ultimate answer,” Dr. Neeland said in an interview. He instead endorsed “advanced imaging for body fat distribution,” such as CT or MRI scans, as his pick for what should be the standard obesity metric, “given that it is much more specific and actionable for both risk assessment and response to therapy. I expect slow but steady advancements that move away from BMI cutoffs, for example for bariatric surgery, given that BMI is an imprecise and crude tool.”

But although imaging with methods like CT and MRI may provide the best accuracy and precision for tracking the volume of a person’s cardiometabolically dangerous fat, they are also hampered by relatively high cost and, for CT and DXA, the issue of radiation exposure.

“CT, MRI, and DXA scans give more in-depth assessment of body composition, but should we expose people to the radiation and the cost?” Dr. Almandoz wondered.

“Height, weight, and waist circumference cost nothing to obtain,” creating a big relative disadvantage for imaging, said Naveed Sattar, MD, professor of metabolic medicine at the University of Glasgow.

“Data would need to show that imaging gives clinicians substantially more information about future risk” to justify its price, Dr. Sattar emphasized.
 

BMI’s limits mean adding on

Regardless of whichever alternatives to BMI end up getting used most, experts generally agree that BMI alone is looking increasingly inadequate.

“Over the next 5 years, BMI will come to be seen as a screening tool that categorizes people into general risk groups” that also needs “other metrics and variables, such as age, race, ethnicity, family history, blood glucose, and blood pressure to better describe health risk in an individual,” predicted Dr. Bessesen.

The endorsement of WHtR by NICE “will lead to more research into how to incorporate WHtR into routine practice. We need more evidence to translate what NICE said into practice,” said Dr. Sattar. “I don’t think we’ll see a shift away from BMI, but we’ll add alternative measures that are particularly useful in certain patients.”

“Because we live in diverse societies, we need to individualize risk assessment and couple that with technology that makes analysis of body composition more accessible,” agreed Dr. Almandoz. He noted that the UT Southwestern weight wellness program where he practices has, for about the past decade, routinely collected waist circumference and bioelectrical impedance data as well as BMI on all people seen in the practice for obesity concerns. Making these additional measurements on a routine basis also helps strengthen patient engagement.

“We get into trouble when we make rigid health policy and clinical decisions based on BMI alone without looking at the patient holistically,” said Dr. Wee. “Patients are more than arbitrary numbers, and clinicians should make clinical decisions based on the totality of evidence for each individual patient.”

Dr. Bessesen, Dr. Wee, Dr. Powell-Wiley, and Dr. Almandoz reported no relevant financial relationships. Dr. Neeland has reported being a consultant for Merck. Dr. Sattar has reported being a consultant or speaker for Abbott Laboratories, Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, MSD, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, and Sanofi.

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

“BMI is trash. Full stop.” This controversial tweet, which received thousands of likes and retweets, was cited in a recent article by one doctor on when physicians might stop using body mass index (BMI) to diagnose obesity.

BMI has for years been the consensus default method for assessing whether a person is overweight or has obesity, and is still widely used as the gatekeeper metric for treatment eligibility for certain weight-loss agents and bariatric surgery.

But growing appreciation of the limitations of BMI is causing many clinicians to consider alternative measures of obesity that can better assess both the amount of adiposity as well as its body location, an important determinant of the cardiometabolic consequences of fat.

Alternative metrics include waist circumference and/or waist-to-height ratio (WHtR); imaging methods such as CT, MRI, and dual-energy x-ray absorptiometry (DXA); and bioelectrical impedance to assess fat volume and location. All have made some inroads on the tight grip BMI has had on obesity assessment.

Chances are, however, that BMI will not fade away anytime soon given how entrenched it has become in clinical practice and for insurance coverage, as well as its relative simplicity and precision.

“BMI is embedded in a wide range of guidelines on the use of medications and surgery. It’s embedded in Food and Drug Administration regulations and for billing and insurance coverage. It would take extremely strong data and years of work to undo the infrastructure built around BMI and replace it with something else. I don’t see that happening [anytime soon],” commented Daniel H. Bessesen, MD, a professor at the University of Colorado at Denver, Aurora, and chief of endocrinology for Denver Health.

“It would be almost impossible to replace all the studies that have used BMI with investigations using some other measure,” he said.
 

BMI Is ‘imperfect’

The entrenched position of BMI as the go-to metric doesn’t keep detractors from weighing in. As noted in a commentary on current clinical challenges surrounding obesity recently published in Annals of Internal Medicine, the journal’s editor-in-chief, Christine Laine, MD, and senior deputy editor Christina C. Wee, MD, listed six top issues clinicians must deal with, one of which, they say, is the need for a better measure of obesity than BMI.

“Unfortunately, BMI is an imperfect measure of body composition that differs with ethnicity, sex, body frame, and muscle mass,” noted Dr. Laine and Dr. Wee.

BMI is based on a person’s weight in kilograms divided by the square of their height in meters. A “healthy” BMI is between 18.5 and 24.9 kg/m2, overweight is 25-29.9, and 30 or greater is considered to represent obesity. However, certain ethnic groups have lower cutoffs for overweight or obesity because of evidence that such individuals can be at higher risk of obesity-related comorbidities at lower BMIs.

“BMI was chosen as the initial screening tool [for obesity] not because anyone thought it was perfect or the best measure but because of its simplicity. All you need is height, weight, and a calculator,” Dr. Wee said in an interview.

Numerous online calculators are available, including one from the Centers for Disease Control and Prevention where height in feet and inches and weight in pounds can be entered to generate the BMI.

BMI is also inherently limited by being “a proxy for adiposity” and not a direct measure, added Dr. Wee, who is also director of the Obesity Research Program of Beth Israel Deaconess Medical Center, Boston.

As such, BMI can’t distinguish between fat and muscle because it relies on weight only to gauge adiposity, noted Tiffany Powell-Wiley, MD, an obesity researcher at the National Heart, Lung, and Blood Institute in Bethesda, Md. Another shortcoming of BMI is that it “is good for distinguishing population-level risk for cardiovascular disease and other chronic diseases, but it does not help as much for distinguishing risk at an individual level,” she said in an interview.

These and other drawbacks have prompted researchers to look for other useful metrics. WHtR, for example, has recently made headway as a potential BMI alternative or complement.
 

The case for WHtR

Concern about overreliance on BMI despite its limitations is not new. In 2015, an American Heart Association scientific statement from the group’s Obesity Committee concluded that “BMI alone, even with lower thresholds, is a useful but not an ideal tool for identification of obesity or assessment of cardiovascular risk,” especially for people from Asian, Black, Hispanic, and Pacific Islander populations.

The writing panel also recommended that clinicians measure waist circumference annually and use that information along with BMI “to better gauge cardiovascular risk in diverse populations.”

Momentum for moving beyond BMI alone has continued to build following the AHA statement.

In September 2022, the National Institute for Health and Care Excellence, which sets policies for the United Kingdom’s National Health Service, revised its guidancefor assessment and management of people with obesity. The updated guidance recommends that when clinicians assess “adults with BMI below 35 kg/m2, measure and use their WHtR, as well as their BMI, as a practical estimate of central adiposity and use these measurements to help to assess and predict health risks.”

NICE released an extensive literature review with the revision, and based on the evidence, said that “using waist-to-height ratio as well as BMI would help give a practical estimate of central adiposity in adults with BMI under 35 kg/m². This would in turn help professionals assess and predict health risks.”

However, the review added that, “because people with a BMI over 35 kg/m² are always likely to have a high WHtR, the committee recognized that it may not be a useful addition for predicting health risks in this group.” The 2022 NICE review also said that it is “important to estimate central adiposity when assessing future health risks, including for people whose BMI is in the healthy-weight category.”

This new emphasis by NICE on measuring and using WHtR as part of obesity assessment “represents an important change in population health policy,” commented Dr. Powell-Wiley. “I expect more professional organizations will endorse use of waist circumference or waist-to-height ratio now that NICE has taken this step,” she predicted.

Waist circumference and WHtR may become standard measures of adiposity in clinical practice over the next 5-10 years.

The recent move by NICE to highlight a complementary role for WHtR “is another acknowledgment that BMI is an imperfect tool for stratifying cardiometabolic risk in a diverse population, especially in people with lower BMIs” because of its variability, commented Jamie Almandoz, MD, medical director of the weight wellness program at UT Southwestern Medical Center, Dallas.
 

WHtR vs. BMI

Another recent step forward for WHtR came with the publication of a post hoc analysis of data collected in the PARADIGM-HF trial, a study that had the primary purpose of comparing two medications for improving outcomes in more than 8,000 patients with heart failure with reduced ejection fraction.

The new analysis showed that “two indices that incorporate waist circumference and height, but not weight, showed a clearer association between greater adiposity and a higher risk of heart failure hospitalization,” compared with BMI.

WHtR was one of the two indices identified as being a better correlate for the adverse effect of excess adiposity compared with BMI.

The authors of the post hoc analysis did not design their analysis to compare WHtR with BMI. Instead, their goal was to better understand what’s known as the “obesity paradox” in people with heart failure with reduced ejection fraction: The recurring observation that, when these patients with heart failure have lower BMIs they fare worse, with higher rates of mortality and adverse cardiovascular outcomes, compared with patients with higher BMIs.

The new analysis showed that this paradox disappeared when WHtR was substituted for BMI as the obesity metric.

This “provides meaningful data about the superiority of WHtR, compared with BMI, for predicting heart failure outcomes,” said Dr. Powell-Wiley, although she cautioned that the analysis was limited by scant data in diverse populations and did not look at other important cardiovascular disease outcomes. While Dr. Powell-Wiley does not think that WHtR needs assessment in a prospective, controlled trial, she called for analysis of pooled prospective studies with more diverse populations to better document the advantages of WHtR over BMI.

The PARADIGM-HF post hoc analysis shows again how flawed BMI is for health assessment and the relative importance of an individualized understanding of a person’s body composition, Dr. Almandoz said in an interview. “As we collect more data, there is increasing awareness of how imperfect BMI is.”
 

Measuring waist circumference is tricky

Although WHtR looks promising as a substitute for or add-on to BMI, it has its own limitations, particularly the challenge of accurately measuring waist circumference.

Measuring waist circumference “not only takes more time but requires the assessor to be well trained about where to put the tape measure and making sure it’s measured at the same place each time,” even when different people take serial measurements from individual patients, noted Dr. Wee. Determining waist circumference can also be technically difficult when done on larger people, she added, and collectively these challenges make waist circumference “less reproducible from measurement to measurement.”

“It’s relatively clear how to standardize measurement of weight and height, but there is a huge amount of variability when the waist is measured,” agreed Dr. Almandoz. “And waist circumference also differs by ethnicity, race, sex, and body frame. There are significant differences in waist circumference levels that associate with increased health risks” between, for example, White and South Asian people.

Another limitation of waist circumference and WHtR is that they “cannot differentiate between visceral and abdominal subcutaneous adipose tissue, which are vastly different regarding cardiometabolic risk, commented Ian Neeland, MD, director of cardiovascular prevention at the University Hospitals Harrington Heart & Vascular Institute, Cleveland.
 

The imaging option

“Waist-to-height ratio is not the ultimate answer,” Dr. Neeland said in an interview. He instead endorsed “advanced imaging for body fat distribution,” such as CT or MRI scans, as his pick for what should be the standard obesity metric, “given that it is much more specific and actionable for both risk assessment and response to therapy. I expect slow but steady advancements that move away from BMI cutoffs, for example for bariatric surgery, given that BMI is an imprecise and crude tool.”

But although imaging with methods like CT and MRI may provide the best accuracy and precision for tracking the volume of a person’s cardiometabolically dangerous fat, they are also hampered by relatively high cost and, for CT and DXA, the issue of radiation exposure.

“CT, MRI, and DXA scans give more in-depth assessment of body composition, but should we expose people to the radiation and the cost?” Dr. Almandoz wondered.

“Height, weight, and waist circumference cost nothing to obtain,” creating a big relative disadvantage for imaging, said Naveed Sattar, MD, professor of metabolic medicine at the University of Glasgow.

“Data would need to show that imaging gives clinicians substantially more information about future risk” to justify its price, Dr. Sattar emphasized.
 

BMI’s limits mean adding on

Regardless of whichever alternatives to BMI end up getting used most, experts generally agree that BMI alone is looking increasingly inadequate.

“Over the next 5 years, BMI will come to be seen as a screening tool that categorizes people into general risk groups” that also needs “other metrics and variables, such as age, race, ethnicity, family history, blood glucose, and blood pressure to better describe health risk in an individual,” predicted Dr. Bessesen.

The endorsement of WHtR by NICE “will lead to more research into how to incorporate WHtR into routine practice. We need more evidence to translate what NICE said into practice,” said Dr. Sattar. “I don’t think we’ll see a shift away from BMI, but we’ll add alternative measures that are particularly useful in certain patients.”

“Because we live in diverse societies, we need to individualize risk assessment and couple that with technology that makes analysis of body composition more accessible,” agreed Dr. Almandoz. He noted that the UT Southwestern weight wellness program where he practices has, for about the past decade, routinely collected waist circumference and bioelectrical impedance data as well as BMI on all people seen in the practice for obesity concerns. Making these additional measurements on a routine basis also helps strengthen patient engagement.

“We get into trouble when we make rigid health policy and clinical decisions based on BMI alone without looking at the patient holistically,” said Dr. Wee. “Patients are more than arbitrary numbers, and clinicians should make clinical decisions based on the totality of evidence for each individual patient.”

Dr. Bessesen, Dr. Wee, Dr. Powell-Wiley, and Dr. Almandoz reported no relevant financial relationships. Dr. Neeland has reported being a consultant for Merck. Dr. Sattar has reported being a consultant or speaker for Abbott Laboratories, Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, MSD, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, and Sanofi.

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

“BMI is trash. Full stop.” This controversial tweet, which received thousands of likes and retweets, was cited in a recent article by one doctor on when physicians might stop using body mass index (BMI) to diagnose obesity.

BMI has for years been the consensus default method for assessing whether a person is overweight or has obesity, and is still widely used as the gatekeeper metric for treatment eligibility for certain weight-loss agents and bariatric surgery.

But growing appreciation of the limitations of BMI is causing many clinicians to consider alternative measures of obesity that can better assess both the amount of adiposity as well as its body location, an important determinant of the cardiometabolic consequences of fat.

Alternative metrics include waist circumference and/or waist-to-height ratio (WHtR); imaging methods such as CT, MRI, and dual-energy x-ray absorptiometry (DXA); and bioelectrical impedance to assess fat volume and location. All have made some inroads on the tight grip BMI has had on obesity assessment.

Chances are, however, that BMI will not fade away anytime soon given how entrenched it has become in clinical practice and for insurance coverage, as well as its relative simplicity and precision.

“BMI is embedded in a wide range of guidelines on the use of medications and surgery. It’s embedded in Food and Drug Administration regulations and for billing and insurance coverage. It would take extremely strong data and years of work to undo the infrastructure built around BMI and replace it with something else. I don’t see that happening [anytime soon],” commented Daniel H. Bessesen, MD, a professor at the University of Colorado at Denver, Aurora, and chief of endocrinology for Denver Health.

“It would be almost impossible to replace all the studies that have used BMI with investigations using some other measure,” he said.
 

BMI Is ‘imperfect’

The entrenched position of BMI as the go-to metric doesn’t keep detractors from weighing in. As noted in a commentary on current clinical challenges surrounding obesity recently published in Annals of Internal Medicine, the journal’s editor-in-chief, Christine Laine, MD, and senior deputy editor Christina C. Wee, MD, listed six top issues clinicians must deal with, one of which, they say, is the need for a better measure of obesity than BMI.

“Unfortunately, BMI is an imperfect measure of body composition that differs with ethnicity, sex, body frame, and muscle mass,” noted Dr. Laine and Dr. Wee.

BMI is based on a person’s weight in kilograms divided by the square of their height in meters. A “healthy” BMI is between 18.5 and 24.9 kg/m2, overweight is 25-29.9, and 30 or greater is considered to represent obesity. However, certain ethnic groups have lower cutoffs for overweight or obesity because of evidence that such individuals can be at higher risk of obesity-related comorbidities at lower BMIs.

“BMI was chosen as the initial screening tool [for obesity] not because anyone thought it was perfect or the best measure but because of its simplicity. All you need is height, weight, and a calculator,” Dr. Wee said in an interview.

Numerous online calculators are available, including one from the Centers for Disease Control and Prevention where height in feet and inches and weight in pounds can be entered to generate the BMI.

BMI is also inherently limited by being “a proxy for adiposity” and not a direct measure, added Dr. Wee, who is also director of the Obesity Research Program of Beth Israel Deaconess Medical Center, Boston.

As such, BMI can’t distinguish between fat and muscle because it relies on weight only to gauge adiposity, noted Tiffany Powell-Wiley, MD, an obesity researcher at the National Heart, Lung, and Blood Institute in Bethesda, Md. Another shortcoming of BMI is that it “is good for distinguishing population-level risk for cardiovascular disease and other chronic diseases, but it does not help as much for distinguishing risk at an individual level,” she said in an interview.

These and other drawbacks have prompted researchers to look for other useful metrics. WHtR, for example, has recently made headway as a potential BMI alternative or complement.
 

The case for WHtR

Concern about overreliance on BMI despite its limitations is not new. In 2015, an American Heart Association scientific statement from the group’s Obesity Committee concluded that “BMI alone, even with lower thresholds, is a useful but not an ideal tool for identification of obesity or assessment of cardiovascular risk,” especially for people from Asian, Black, Hispanic, and Pacific Islander populations.

The writing panel also recommended that clinicians measure waist circumference annually and use that information along with BMI “to better gauge cardiovascular risk in diverse populations.”

Momentum for moving beyond BMI alone has continued to build following the AHA statement.

In September 2022, the National Institute for Health and Care Excellence, which sets policies for the United Kingdom’s National Health Service, revised its guidancefor assessment and management of people with obesity. The updated guidance recommends that when clinicians assess “adults with BMI below 35 kg/m2, measure and use their WHtR, as well as their BMI, as a practical estimate of central adiposity and use these measurements to help to assess and predict health risks.”

NICE released an extensive literature review with the revision, and based on the evidence, said that “using waist-to-height ratio as well as BMI would help give a practical estimate of central adiposity in adults with BMI under 35 kg/m². This would in turn help professionals assess and predict health risks.”

However, the review added that, “because people with a BMI over 35 kg/m² are always likely to have a high WHtR, the committee recognized that it may not be a useful addition for predicting health risks in this group.” The 2022 NICE review also said that it is “important to estimate central adiposity when assessing future health risks, including for people whose BMI is in the healthy-weight category.”

This new emphasis by NICE on measuring and using WHtR as part of obesity assessment “represents an important change in population health policy,” commented Dr. Powell-Wiley. “I expect more professional organizations will endorse use of waist circumference or waist-to-height ratio now that NICE has taken this step,” she predicted.

Waist circumference and WHtR may become standard measures of adiposity in clinical practice over the next 5-10 years.

The recent move by NICE to highlight a complementary role for WHtR “is another acknowledgment that BMI is an imperfect tool for stratifying cardiometabolic risk in a diverse population, especially in people with lower BMIs” because of its variability, commented Jamie Almandoz, MD, medical director of the weight wellness program at UT Southwestern Medical Center, Dallas.
 

WHtR vs. BMI

Another recent step forward for WHtR came with the publication of a post hoc analysis of data collected in the PARADIGM-HF trial, a study that had the primary purpose of comparing two medications for improving outcomes in more than 8,000 patients with heart failure with reduced ejection fraction.

The new analysis showed that “two indices that incorporate waist circumference and height, but not weight, showed a clearer association between greater adiposity and a higher risk of heart failure hospitalization,” compared with BMI.

WHtR was one of the two indices identified as being a better correlate for the adverse effect of excess adiposity compared with BMI.

The authors of the post hoc analysis did not design their analysis to compare WHtR with BMI. Instead, their goal was to better understand what’s known as the “obesity paradox” in people with heart failure with reduced ejection fraction: The recurring observation that, when these patients with heart failure have lower BMIs they fare worse, with higher rates of mortality and adverse cardiovascular outcomes, compared with patients with higher BMIs.

The new analysis showed that this paradox disappeared when WHtR was substituted for BMI as the obesity metric.

This “provides meaningful data about the superiority of WHtR, compared with BMI, for predicting heart failure outcomes,” said Dr. Powell-Wiley, although she cautioned that the analysis was limited by scant data in diverse populations and did not look at other important cardiovascular disease outcomes. While Dr. Powell-Wiley does not think that WHtR needs assessment in a prospective, controlled trial, she called for analysis of pooled prospective studies with more diverse populations to better document the advantages of WHtR over BMI.

The PARADIGM-HF post hoc analysis shows again how flawed BMI is for health assessment and the relative importance of an individualized understanding of a person’s body composition, Dr. Almandoz said in an interview. “As we collect more data, there is increasing awareness of how imperfect BMI is.”
 

Measuring waist circumference is tricky

Although WHtR looks promising as a substitute for or add-on to BMI, it has its own limitations, particularly the challenge of accurately measuring waist circumference.

Measuring waist circumference “not only takes more time but requires the assessor to be well trained about where to put the tape measure and making sure it’s measured at the same place each time,” even when different people take serial measurements from individual patients, noted Dr. Wee. Determining waist circumference can also be technically difficult when done on larger people, she added, and collectively these challenges make waist circumference “less reproducible from measurement to measurement.”

“It’s relatively clear how to standardize measurement of weight and height, but there is a huge amount of variability when the waist is measured,” agreed Dr. Almandoz. “And waist circumference also differs by ethnicity, race, sex, and body frame. There are significant differences in waist circumference levels that associate with increased health risks” between, for example, White and South Asian people.

Another limitation of waist circumference and WHtR is that they “cannot differentiate between visceral and abdominal subcutaneous adipose tissue, which are vastly different regarding cardiometabolic risk, commented Ian Neeland, MD, director of cardiovascular prevention at the University Hospitals Harrington Heart & Vascular Institute, Cleveland.
 

The imaging option

“Waist-to-height ratio is not the ultimate answer,” Dr. Neeland said in an interview. He instead endorsed “advanced imaging for body fat distribution,” such as CT or MRI scans, as his pick for what should be the standard obesity metric, “given that it is much more specific and actionable for both risk assessment and response to therapy. I expect slow but steady advancements that move away from BMI cutoffs, for example for bariatric surgery, given that BMI is an imprecise and crude tool.”

But although imaging with methods like CT and MRI may provide the best accuracy and precision for tracking the volume of a person’s cardiometabolically dangerous fat, they are also hampered by relatively high cost and, for CT and DXA, the issue of radiation exposure.

“CT, MRI, and DXA scans give more in-depth assessment of body composition, but should we expose people to the radiation and the cost?” Dr. Almandoz wondered.

“Height, weight, and waist circumference cost nothing to obtain,” creating a big relative disadvantage for imaging, said Naveed Sattar, MD, professor of metabolic medicine at the University of Glasgow.

“Data would need to show that imaging gives clinicians substantially more information about future risk” to justify its price, Dr. Sattar emphasized.
 

BMI’s limits mean adding on

Regardless of whichever alternatives to BMI end up getting used most, experts generally agree that BMI alone is looking increasingly inadequate.

“Over the next 5 years, BMI will come to be seen as a screening tool that categorizes people into general risk groups” that also needs “other metrics and variables, such as age, race, ethnicity, family history, blood glucose, and blood pressure to better describe health risk in an individual,” predicted Dr. Bessesen.

The endorsement of WHtR by NICE “will lead to more research into how to incorporate WHtR into routine practice. We need more evidence to translate what NICE said into practice,” said Dr. Sattar. “I don’t think we’ll see a shift away from BMI, but we’ll add alternative measures that are particularly useful in certain patients.”

“Because we live in diverse societies, we need to individualize risk assessment and couple that with technology that makes analysis of body composition more accessible,” agreed Dr. Almandoz. He noted that the UT Southwestern weight wellness program where he practices has, for about the past decade, routinely collected waist circumference and bioelectrical impedance data as well as BMI on all people seen in the practice for obesity concerns. Making these additional measurements on a routine basis also helps strengthen patient engagement.

“We get into trouble when we make rigid health policy and clinical decisions based on BMI alone without looking at the patient holistically,” said Dr. Wee. “Patients are more than arbitrary numbers, and clinicians should make clinical decisions based on the totality of evidence for each individual patient.”

Dr. Bessesen, Dr. Wee, Dr. Powell-Wiley, and Dr. Almandoz reported no relevant financial relationships. Dr. Neeland has reported being a consultant for Merck. Dr. Sattar has reported being a consultant or speaker for Abbott Laboratories, Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, MSD, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, and Sanofi.

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