Article

In September 2021, a community in Virginia experienced an outbreak of hepatitis A virus (HAV) that was ultimately linked to an infected food handler.¹ A total of 149 cases were reported over the next 12 months; 51 were directly related to the food handler and the remainder were the result of sustained community transmission. Of the 51 people who were directly infected by the food handler, 31 were hospitalized and 3 died. This incident offers important reminders about public health surveillance and the role that family physicians can play.

Hepatitis A virus is transmitted through food and drinks that have been contaminated by small amounts of stool that contains the virus or through close contact (including sexual contact) with a person who is infected. The incubation period can range from 15 to 59 days.

HAV generally resolves in a few days to weeks, with no long-term effects. However, recent outbreaks have been associated with high hospitalization and mortality rates because of the underlying comorbidities of those infected.

An increase in incidence. The national rate of HAV infection reached a low of less than 1/100,000 in 2015 but has since increased to almost 6/100,000 in 2019. This increase is mostly due to outbreaks linked to spread among people without a fixed residence, those who use illicit drugs, and men who have sex with men.²

In the Virginia outbreak, the food handler had a risk factor for HAV and was unvaccinated. He worked at 3 different locations of a restaurant chain for a total of 16 days while infectious, preparing ready-to-eat food without using gloves. Furthermore, he delayed seeking medical care for more than 2 weeks—at which time, the nature of his employment was not disclosed.

Prevention is straightforward. HAV infection can be prevented by administration of either HAV vaccine or immune globulin within 2 weeks of exposure.³ During an HAV outbreak, vaccination is recommended for people considered to be at risk, including those without a fixed residence, those who use illicit drugs, those who travel internationally, and men who have sex with men.³

There are 3 HAV vaccines available in the United States: 2 single-antigen vaccines, Havrix and Vaqta, both approved for children and adults, and a combination vaccine (containing both HAV and hepatitis B antigens), Twinrix, which is approved for those ages 18 years and older. All are inactivated vaccines.

What you can do. The Virginia outbreak illustrates the important role that family physicians can and do play in public health. We should:

• Encourage adults with risk factors for HAV to be vaccinated.
• Ask those with an HAV diagnosis about the people they may have exposed through personal contact or occupational exposure.
• Promptly report infectious diseases that are designated “reportable” to the public health department.
• Immediately report (by telephone) when HAV and other enteric infections involve a food handler.

In September 2021, a community in Virginia experienced an outbreak of hepatitis A virus (HAV) that was ultimately linked to an infected food handler.¹ A total of 149 cases were reported over the next 12 months; 51 were directly related to the food handler and the remainder were the result of sustained community transmission. Of the 51 people who were directly infected by the food handler, 31 were hospitalized and 3 died. This incident offers important reminders about public health surveillance and the role that family physicians can play.

Hepatitis A virus is transmitted through food and drinks that have been contaminated by small amounts of stool that contains the virus or through close contact (including sexual contact) with a person who is infected. The incubation period can range from 15 to 59 days.

HAV generally resolves in a few days to weeks, with no long-term effects. However, recent outbreaks have been associated with high hospitalization and mortality rates because of the underlying comorbidities of those infected.

An increase in incidence. The national rate of HAV infection reached a low of less than 1/100,000 in 2015 but has since increased to almost 6/100,000 in 2019. This increase is mostly due to outbreaks linked to spread among people without a fixed residence, those who use illicit drugs, and men who have sex with men.²

In the Virginia outbreak, the food handler had a risk factor for HAV and was unvaccinated. He worked at 3 different locations of a restaurant chain for a total of 16 days while infectious, preparing ready-to-eat food without using gloves. Furthermore, he delayed seeking medical care for more than 2 weeks—at which time, the nature of his employment was not disclosed.

Prevention is straightforward. HAV infection can be prevented by administration of either HAV vaccine or immune globulin within 2 weeks of exposure.³ During an HAV outbreak, vaccination is recommended for people considered to be at risk, including those without a fixed residence, those who use illicit drugs, those who travel internationally, and men who have sex with men.³

There are 3 HAV vaccines available in the United States: 2 single-antigen vaccines, Havrix and Vaqta, both approved for children and adults, and a combination vaccine (containing both HAV and hepatitis B antigens), Twinrix, which is approved for those ages 18 years and older. All are inactivated vaccines.

What you can do. The Virginia outbreak illustrates the important role that family physicians can and do play in public health. We should:

• Encourage adults with risk factors for HAV to be vaccinated.
• Ask those with an HAV diagnosis about the people they may have exposed through personal contact or occupational exposure.
• Promptly report infectious diseases that are designated “reportable” to the public health department.
• Immediately report (by telephone) when HAV and other enteric infections involve a food handler.

In September 2021, a community in Virginia experienced an outbreak of hepatitis A virus (HAV) that was ultimately linked to an infected food handler.¹ A total of 149 cases were reported over the next 12 months; 51 were directly related to the food handler and the remainder were the result of sustained community transmission. Of the 51 people who were directly infected by the food handler, 31 were hospitalized and 3 died. This incident offers important reminders about public health surveillance and the role that family physicians can play.

Hepatitis A virus is transmitted through food and drinks that have been contaminated by small amounts of stool that contains the virus or through close contact (including sexual contact) with a person who is infected. The incubation period can range from 15 to 59 days.

HAV generally resolves in a few days to weeks, with no long-term effects. However, recent outbreaks have been associated with high hospitalization and mortality rates because of the underlying comorbidities of those infected.

An increase in incidence. The national rate of HAV infection reached a low of less than 1/100,000 in 2015 but has since increased to almost 6/100,000 in 2019. This increase is mostly due to outbreaks linked to spread among people without a fixed residence, those who use illicit drugs, and men who have sex with men.²

In the Virginia outbreak, the food handler had a risk factor for HAV and was unvaccinated. He worked at 3 different locations of a restaurant chain for a total of 16 days while infectious, preparing ready-to-eat food without using gloves. Furthermore, he delayed seeking medical care for more than 2 weeks—at which time, the nature of his employment was not disclosed.

Prevention is straightforward. HAV infection can be prevented by administration of either HAV vaccine or immune globulin within 2 weeks of exposure.³ During an HAV outbreak, vaccination is recommended for people considered to be at risk, including those without a fixed residence, those who use illicit drugs, those who travel internationally, and men who have sex with men.³

There are 3 HAV vaccines available in the United States: 2 single-antigen vaccines, Havrix and Vaqta, both approved for children and adults, and a combination vaccine (containing both HAV and hepatitis B antigens), Twinrix, which is approved for those ages 18 years and older. All are inactivated vaccines.

What you can do. The Virginia outbreak illustrates the important role that family physicians can and do play in public health. We should:

• Encourage adults with risk factors for HAV to be vaccinated.
• Ask those with an HAV diagnosis about the people they may have exposed through personal contact or occupational exposure.
• Promptly report infectious diseases that are designated “reportable” to the public health department.
• Immediately report (by telephone) when HAV and other enteric infections involve a food handler.

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.

Key clinical point: Rheumatoid arthritis (RA) is associated with a significant increase in the risk for ischemic heart disease (IHD) and myocardial infarction (MI), and managing RA activity may reduce the risk for cardiovascular diseases.

Major finding: RA is significantly associated with an increased risk for IHD (odds ratio [OR] 1.0006; P  =  .001551915) and MI (OR 1.0458; P  =  .001636), but not arrhythmia and atrial fibrillation.

Study details: Findings are from a two-sample Mendelian randomization study including patients and matched control individuals for RA (n = 14,361 and n = 43,923, respectively), MI (n = 12,801 and n = 187,840, respectively), IHD (n = 5861 and n = 457,149, respectively), atrial fibrillation (n = 60,620 and n = 970,216, respectively), and arrhythmia (n = 2545 and n = 460,388, respectively).

Disclosures: This study was supported by the Young Talent Development Plan of Changzhou Health Commission, China, and other sources. The authors declared no conflicts of interest.

Source: Wang M et al. Relationship between rheumatoid arthritis and cardiovascular comorbidity, causation or co-occurrence: A Mendelian randomization study. Front Cardiovasc Med. 2023;10:1099861 (Mar 17). Doi: 10.3389/fcvm.2023.1099861

Key clinical point: Rheumatoid arthritis (RA) is associated with a significant increase in the risk for ischemic heart disease (IHD) and myocardial infarction (MI), and managing RA activity may reduce the risk for cardiovascular diseases.

Major finding: RA is significantly associated with an increased risk for IHD (odds ratio [OR] 1.0006; P  =  .001551915) and MI (OR 1.0458; P  =  .001636), but not arrhythmia and atrial fibrillation.

Study details: Findings are from a two-sample Mendelian randomization study including patients and matched control individuals for RA (n = 14,361 and n = 43,923, respectively), MI (n = 12,801 and n = 187,840, respectively), IHD (n = 5861 and n = 457,149, respectively), atrial fibrillation (n = 60,620 and n = 970,216, respectively), and arrhythmia (n = 2545 and n = 460,388, respectively).

Disclosures: This study was supported by the Young Talent Development Plan of Changzhou Health Commission, China, and other sources. The authors declared no conflicts of interest.

Source: Wang M et al. Relationship between rheumatoid arthritis and cardiovascular comorbidity, causation or co-occurrence: A Mendelian randomization study. Front Cardiovasc Med. 2023;10:1099861 (Mar 17). Doi: 10.3389/fcvm.2023.1099861

Key clinical point: Rheumatoid arthritis (RA) is associated with a significant increase in the risk for ischemic heart disease (IHD) and myocardial infarction (MI), and managing RA activity may reduce the risk for cardiovascular diseases.

Major finding: RA is significantly associated with an increased risk for IHD (odds ratio [OR] 1.0006; P  =  .001551915) and MI (OR 1.0458; P  =  .001636), but not arrhythmia and atrial fibrillation.

Study details: Findings are from a two-sample Mendelian randomization study including patients and matched control individuals for RA (n = 14,361 and n = 43,923, respectively), MI (n = 12,801 and n = 187,840, respectively), IHD (n = 5861 and n = 457,149, respectively), atrial fibrillation (n = 60,620 and n = 970,216, respectively), and arrhythmia (n = 2545 and n = 460,388, respectively).

Disclosures: This study was supported by the Young Talent Development Plan of Changzhou Health Commission, China, and other sources. The authors declared no conflicts of interest.

Source: Wang M et al. Relationship between rheumatoid arthritis and cardiovascular comorbidity, causation or co-occurrence: A Mendelian randomization study. Front Cardiovasc Med. 2023;10:1099861 (Mar 17). Doi: 10.3389/fcvm.2023.1099861

Key clinical point: Mortality risk varied with time and increased only during the second not the first decade after the diagnosis of rheumatoid arthritis (RA), with respiratory diseases potentially surpassing cardiovascular diseases as major attributable factors.

Major finding: Increase in mortality was observed at 20 years (standardized mortality ratio [SMR] 1.49; P < .001) but not during the first 10 years (P  =  .44) after RA diagnosis, with pneumonia (cause-specific SMR 5.22; 95% CI 2.26-10.29) and interstitial lung disease (cause-specific SMR 7.64; 95% CI 2.98-14.69) being major contributors.

Study details: Findings are from an analysis of 1895 patients with RA from the Australian Rheumatology Association Database (ARAD) registry who received biologic, targeted synthetic, or conventional synthetic disease-modifying antirheumatic drugs.

Disclosures: ARAD received support through the Australian Rheumatology Association from various sources. Three authors declared receiving grants, funding, or honoraria from different sources unrelated to this study.

Source: Black RJ et al. Mortality estimates and excess mortality in rheumatoid arthritis. Rheumatology (Oxford). 2023 (Mar 15). Doi: 10.1093/rheumatology/kead106

Key clinical point: Mortality risk varied with time and increased only during the second not the first decade after the diagnosis of rheumatoid arthritis (RA), with respiratory diseases potentially surpassing cardiovascular diseases as major attributable factors.

Major finding: Increase in mortality was observed at 20 years (standardized mortality ratio [SMR] 1.49; P < .001) but not during the first 10 years (P  =  .44) after RA diagnosis, with pneumonia (cause-specific SMR 5.22; 95% CI 2.26-10.29) and interstitial lung disease (cause-specific SMR 7.64; 95% CI 2.98-14.69) being major contributors.

Study details: Findings are from an analysis of 1895 patients with RA from the Australian Rheumatology Association Database (ARAD) registry who received biologic, targeted synthetic, or conventional synthetic disease-modifying antirheumatic drugs.

Disclosures: ARAD received support through the Australian Rheumatology Association from various sources. Three authors declared receiving grants, funding, or honoraria from different sources unrelated to this study.

Source: Black RJ et al. Mortality estimates and excess mortality in rheumatoid arthritis. Rheumatology (Oxford). 2023 (Mar 15). Doi: 10.1093/rheumatology/kead106

Key clinical point: Mortality risk varied with time and increased only during the second not the first decade after the diagnosis of rheumatoid arthritis (RA), with respiratory diseases potentially surpassing cardiovascular diseases as major attributable factors.

Major finding: Increase in mortality was observed at 20 years (standardized mortality ratio [SMR] 1.49; P < .001) but not during the first 10 years (P  =  .44) after RA diagnosis, with pneumonia (cause-specific SMR 5.22; 95% CI 2.26-10.29) and interstitial lung disease (cause-specific SMR 7.64; 95% CI 2.98-14.69) being major contributors.

Study details: Findings are from an analysis of 1895 patients with RA from the Australian Rheumatology Association Database (ARAD) registry who received biologic, targeted synthetic, or conventional synthetic disease-modifying antirheumatic drugs.

Disclosures: ARAD received support through the Australian Rheumatology Association from various sources. Three authors declared receiving grants, funding, or honoraria from different sources unrelated to this study.

Source: Black RJ et al. Mortality estimates and excess mortality in rheumatoid arthritis. Rheumatology (Oxford). 2023 (Mar 15). Doi: 10.1093/rheumatology/kead106

Key clinical point: Rheumatoid arthritis (RA) was significantly associated with an increased risk for bronchial asthma, allergic rhinitis, and sinusitis, and a notable interrelation was observed between the presence of asthma and obesity in patients with RA.

Major finding: Presence of RA significantly increased the risk for asthma (odds ratio [OR] 2.32; 95% CI 1.51-3.57), allergic rhinitis (OR 1.51; 95% CI 1.08-2.10), and sinusitis (OR 1.64; 95% CI 1.08-2.50) in the whole cohort and the prevalence of obesity in patients with asthma (64.0% vs 40.2%; P  =  .034).

Study details: This population-based cross-sectional study included 14,272 participants, of which 334 had RA.

Disclosures: This study was supported by the National Research Foundation of Korea grant funded by the Korean Government. The authors declared no conflicts of interest.

Source: Kim JG et al. Association of rheumatoid arthritis with bronchial asthma and asthma-related comorbidities: A population-based national surveillance study. Front Med (Lausanne). 2023;10:1006290 (Mar 10). Doi: 10.3389/fmed.2023.1006290

Key clinical point: Rheumatoid arthritis (RA) was significantly associated with an increased risk for bronchial asthma, allergic rhinitis, and sinusitis, and a notable interrelation was observed between the presence of asthma and obesity in patients with RA.

Major finding: Presence of RA significantly increased the risk for asthma (odds ratio [OR] 2.32; 95% CI 1.51-3.57), allergic rhinitis (OR 1.51; 95% CI 1.08-2.10), and sinusitis (OR 1.64; 95% CI 1.08-2.50) in the whole cohort and the prevalence of obesity in patients with asthma (64.0% vs 40.2%; P  =  .034).

Study details: This population-based cross-sectional study included 14,272 participants, of which 334 had RA.

Disclosures: This study was supported by the National Research Foundation of Korea grant funded by the Korean Government. The authors declared no conflicts of interest.

Source: Kim JG et al. Association of rheumatoid arthritis with bronchial asthma and asthma-related comorbidities: A population-based national surveillance study. Front Med (Lausanne). 2023;10:1006290 (Mar 10). Doi: 10.3389/fmed.2023.1006290

Key clinical point: Rheumatoid arthritis (RA) was significantly associated with an increased risk for bronchial asthma, allergic rhinitis, and sinusitis, and a notable interrelation was observed between the presence of asthma and obesity in patients with RA.

Major finding: Presence of RA significantly increased the risk for asthma (odds ratio [OR] 2.32; 95% CI 1.51-3.57), allergic rhinitis (OR 1.51; 95% CI 1.08-2.10), and sinusitis (OR 1.64; 95% CI 1.08-2.50) in the whole cohort and the prevalence of obesity in patients with asthma (64.0% vs 40.2%; P  =  .034).

Study details: This population-based cross-sectional study included 14,272 participants, of which 334 had RA.

Disclosures: This study was supported by the National Research Foundation of Korea grant funded by the Korean Government. The authors declared no conflicts of interest.

Source: Kim JG et al. Association of rheumatoid arthritis with bronchial asthma and asthma-related comorbidities: A population-based national surveillance study. Front Med (Lausanne). 2023;10:1006290 (Mar 10). Doi: 10.3389/fmed.2023.1006290

Key clinical point: Abatacept with or without conventional synthetic disease-modifying antirheumatic drugs (csDMARD) demonstrated better efficacy and favorable safety outcomes compared with placebo, csDMARD, or other biologic DMARD (bDMARD) in patients with rheumatoid arthritis (RA).

Major finding: Patients treated with abatacept with or without csDMARD vs placebo, csDMARD, or other bDMARD were more likely to achieve American College of Rheumatology (ACR) 20 (relative risk [RR] 1.57; 95% CI 1.27-1.93), ACR50 (RR 1.84; 95% CI 1.38-2.44), and ACR70 (RR 2.36; 95% CI 1.60-3.47) responses, as well as were less likely to experience adverse events (RR 0.93; 95% CI 0.84-1.03).

Study details: Findings are from a systematic review and meta-analysis of 13 randomized controlled trials including 5978 patients with RA who were randomly assigned to receive abatacept alone, abatacept with csDMARD, placebo, csDMARD, or other bDMARD.

Disclosures: This study was supported by the National Key R&D Program of China. The authors did not report conflicts of interest.

Source: Ahamada MM and Wu X. Analysis of efficacy and safety of abatacept for rheumatoid arthritis: Systematic review and meta-analysis. Clin Exp Rheumatol. 2023 (Mar 7). Doi: 10.55563/clinexprheumatol/2xjg0d

Key clinical point: Abatacept with or without conventional synthetic disease-modifying antirheumatic drugs (csDMARD) demonstrated better efficacy and favorable safety outcomes compared with placebo, csDMARD, or other biologic DMARD (bDMARD) in patients with rheumatoid arthritis (RA).

Major finding: Patients treated with abatacept with or without csDMARD vs placebo, csDMARD, or other bDMARD were more likely to achieve American College of Rheumatology (ACR) 20 (relative risk [RR] 1.57; 95% CI 1.27-1.93), ACR50 (RR 1.84; 95% CI 1.38-2.44), and ACR70 (RR 2.36; 95% CI 1.60-3.47) responses, as well as were less likely to experience adverse events (RR 0.93; 95% CI 0.84-1.03).

Study details: Findings are from a systematic review and meta-analysis of 13 randomized controlled trials including 5978 patients with RA who were randomly assigned to receive abatacept alone, abatacept with csDMARD, placebo, csDMARD, or other bDMARD.

Disclosures: This study was supported by the National Key R&D Program of China. The authors did not report conflicts of interest.

Source: Ahamada MM and Wu X. Analysis of efficacy and safety of abatacept for rheumatoid arthritis: Systematic review and meta-analysis. Clin Exp Rheumatol. 2023 (Mar 7). Doi: 10.55563/clinexprheumatol/2xjg0d

Key clinical point: Abatacept with or without conventional synthetic disease-modifying antirheumatic drugs (csDMARD) demonstrated better efficacy and favorable safety outcomes compared with placebo, csDMARD, or other biologic DMARD (bDMARD) in patients with rheumatoid arthritis (RA).

Major finding: Patients treated with abatacept with or without csDMARD vs placebo, csDMARD, or other bDMARD were more likely to achieve American College of Rheumatology (ACR) 20 (relative risk [RR] 1.57; 95% CI 1.27-1.93), ACR50 (RR 1.84; 95% CI 1.38-2.44), and ACR70 (RR 2.36; 95% CI 1.60-3.47) responses, as well as were less likely to experience adverse events (RR 0.93; 95% CI 0.84-1.03).

Study details: Findings are from a systematic review and meta-analysis of 13 randomized controlled trials including 5978 patients with RA who were randomly assigned to receive abatacept alone, abatacept with csDMARD, placebo, csDMARD, or other bDMARD.

Disclosures: This study was supported by the National Key R&D Program of China. The authors did not report conflicts of interest.

Source: Ahamada MM and Wu X. Analysis of efficacy and safety of abatacept for rheumatoid arthritis: Systematic review and meta-analysis. Clin Exp Rheumatol. 2023 (Mar 7). Doi: 10.55563/clinexprheumatol/2xjg0d

Key clinical point: Factors like age ≥65 years or current or former smoking accounted for excess risk with tofacitinib vs tumor necrosis factor inhibitor (TNFi) use in patients with rheumatoid arthritis (RA).

Major finding: Tofacitinib vs TNFi significantly increased the risk for malignancies (hazard ratio [HR] 1.55; 95% CI 1.05-2.30), venous thromboembolism (HR 5.19; 95% CI 1.86-14.46), and all-cause death (HR 2.24; 95% CI 1.20-4.19) among patients who were ≥65 years old or ever smokers, but not among those aged <65 years and never smokers.

Study details: Findings are from a post hoc analysis of the ORAL Surveillance trial including patients with RA (n = 4362) treated with tofacitinib or TNFi and an exploratory analysis of RA, PsA, and ulcerative colitis (UC) development programs including tofacitinib-exposed patients with RA (n = 7964), psoriatic arthritis (n = 783), and UC (n = 1157).

Disclosures: This study was sponsored by Pfizer Inc. Six authors declared being employees and stockholders of Pfizer. Two authors declared receiving speaking, consulting, or lecture fees or research grants from Pfizer and other sources.

Source: Kristensen LE et al. Identification of two tofacitinib subpopulations with different relative risk versus TNF inhibitors: An analysis of the open label, randomised controlled study ORAL Surveillance. Ann Rheum Dis. 2023 (Mar 17). Doi: 10.1136/ard-2022-223715

Key clinical point: Factors like age ≥65 years or current or former smoking accounted for excess risk with tofacitinib vs tumor necrosis factor inhibitor (TNFi) use in patients with rheumatoid arthritis (RA).

Major finding: Tofacitinib vs TNFi significantly increased the risk for malignancies (hazard ratio [HR] 1.55; 95% CI 1.05-2.30), venous thromboembolism (HR 5.19; 95% CI 1.86-14.46), and all-cause death (HR 2.24; 95% CI 1.20-4.19) among patients who were ≥65 years old or ever smokers, but not among those aged <65 years and never smokers.

Study details: Findings are from a post hoc analysis of the ORAL Surveillance trial including patients with RA (n = 4362) treated with tofacitinib or TNFi and an exploratory analysis of RA, PsA, and ulcerative colitis (UC) development programs including tofacitinib-exposed patients with RA (n = 7964), psoriatic arthritis (n = 783), and UC (n = 1157).

Disclosures: This study was sponsored by Pfizer Inc. Six authors declared being employees and stockholders of Pfizer. Two authors declared receiving speaking, consulting, or lecture fees or research grants from Pfizer and other sources.

Source: Kristensen LE et al. Identification of two tofacitinib subpopulations with different relative risk versus TNF inhibitors: An analysis of the open label, randomised controlled study ORAL Surveillance. Ann Rheum Dis. 2023 (Mar 17). Doi: 10.1136/ard-2022-223715

Key clinical point: Factors like age ≥65 years or current or former smoking accounted for excess risk with tofacitinib vs tumor necrosis factor inhibitor (TNFi) use in patients with rheumatoid arthritis (RA).

Major finding: Tofacitinib vs TNFi significantly increased the risk for malignancies (hazard ratio [HR] 1.55; 95% CI 1.05-2.30), venous thromboembolism (HR 5.19; 95% CI 1.86-14.46), and all-cause death (HR 2.24; 95% CI 1.20-4.19) among patients who were ≥65 years old or ever smokers, but not among those aged <65 years and never smokers.

Study details: Findings are from a post hoc analysis of the ORAL Surveillance trial including patients with RA (n = 4362) treated with tofacitinib or TNFi and an exploratory analysis of RA, PsA, and ulcerative colitis (UC) development programs including tofacitinib-exposed patients with RA (n = 7964), psoriatic arthritis (n = 783), and UC (n = 1157).

Disclosures: This study was sponsored by Pfizer Inc. Six authors declared being employees and stockholders of Pfizer. Two authors declared receiving speaking, consulting, or lecture fees or research grants from Pfizer and other sources.

Source: Kristensen LE et al. Identification of two tofacitinib subpopulations with different relative risk versus TNF inhibitors: An analysis of the open label, randomised controlled study ORAL Surveillance. Ann Rheum Dis. 2023 (Mar 17). Doi: 10.1136/ard-2022-223715

Key clinical point: Risk for severe infections significantly increased in patients who were newly diagnosed with rheumatoid arthritis (RA) after initiating biologic disease-modifying antirheumatic drugs (bDMARD).

Major finding: Over a period of 8 years, severe infection rates significantly increased in patients who were newly diagnosed with RA after initiating bDMARD (adjusted difference between pre- and post-bDMARD rates [Δ] 1.85; P  =  .001), whereas no significant change was observed in control individuals from the general population (Δ 0.12; P  =  .29).

Study details: Findings are from a population-based retrospective cohort study including 60,226 patients with newly diagnosed RA and 588,499 age- and sex-matched control individuals without any inflammatory arthritis from the general population who initiated bDMARD.

Disclosures: This study was supported by the Canadian Institute of Health Research and other sources. The authors declared no conflicts of interest.

Source: Zhou VY et al. Risk of severe infections after the introduction of biologic DMARDs in people with newly diagnosed rheumatoid arthritis: A population-based interrupted time-series analysis. Rheumatology (Oxford). 2023 (Apr 4). Doi: 10.1093/rheumatology/kead158

Key clinical point: Risk for severe infections significantly increased in patients who were newly diagnosed with rheumatoid arthritis (RA) after initiating biologic disease-modifying antirheumatic drugs (bDMARD).

Major finding: Over a period of 8 years, severe infection rates significantly increased in patients who were newly diagnosed with RA after initiating bDMARD (adjusted difference between pre- and post-bDMARD rates [Δ] 1.85; P  =  .001), whereas no significant change was observed in control individuals from the general population (Δ 0.12; P  =  .29).

Study details: Findings are from a population-based retrospective cohort study including 60,226 patients with newly diagnosed RA and 588,499 age- and sex-matched control individuals without any inflammatory arthritis from the general population who initiated bDMARD.

Disclosures: This study was supported by the Canadian Institute of Health Research and other sources. The authors declared no conflicts of interest.

Source: Zhou VY et al. Risk of severe infections after the introduction of biologic DMARDs in people with newly diagnosed rheumatoid arthritis: A population-based interrupted time-series analysis. Rheumatology (Oxford). 2023 (Apr 4). Doi: 10.1093/rheumatology/kead158

Key clinical point: Risk for severe infections significantly increased in patients who were newly diagnosed with rheumatoid arthritis (RA) after initiating biologic disease-modifying antirheumatic drugs (bDMARD).

Major finding: Over a period of 8 years, severe infection rates significantly increased in patients who were newly diagnosed with RA after initiating bDMARD (adjusted difference between pre- and post-bDMARD rates [Δ] 1.85; P  =  .001), whereas no significant change was observed in control individuals from the general population (Δ 0.12; P  =  .29).

Study details: Findings are from a population-based retrospective cohort study including 60,226 patients with newly diagnosed RA and 588,499 age- and sex-matched control individuals without any inflammatory arthritis from the general population who initiated bDMARD.

Disclosures: This study was supported by the Canadian Institute of Health Research and other sources. The authors declared no conflicts of interest.

Source: Zhou VY et al. Risk of severe infections after the introduction of biologic DMARDs in people with newly diagnosed rheumatoid arthritis: A population-based interrupted time-series analysis. Rheumatology (Oxford). 2023 (Apr 4). Doi: 10.1093/rheumatology/kead158

Key clinical point: Patients with rheumatoid arthritis (RA) treated with tofacitinib had a 69% lower risk of developing interstitial lung disease (ILD) than those treated with adalimumab.

Major finding: Compared with adalimumab, tofacitinib resulted in the lowest incidence of ILD (incidence rate ratio 0.43; 95% CI 0.18-1.05), followed by abatacept, tocilizumab, and rituximab. Tofacitinib was associated with a significant 69% reduced risk of developing ILD compared with adalimumab (adjusted hazard ratio 0.31; P  =  .009).

Study details: Findings are from a retrospective cohort study including 28,559 patients with RA without preexisting ILD who were newly administered adalimumab, abatacept, rituximab, tocilizumab, or tofacitinib, of which 276 patients were diagnosed with incident ILD.

Disclosures: This study was supported by the US National Institutes of Health and other sources. The authors did not report conflicts of interest.

Source: Baker MC et al. Incidence of interstitial lung disease in patients with rheumatoid arthritis treated with biologic and targeted synthetic disease-modifying antirheumatic drugs. JAMA Netw Open. 2023;6(3):e233640 (Mar 20). Doi: 10.1001/jamanetworkopen.2023.3640

Key clinical point: Patients with rheumatoid arthritis (RA) treated with tofacitinib had a 69% lower risk of developing interstitial lung disease (ILD) than those treated with adalimumab.

Major finding: Compared with adalimumab, tofacitinib resulted in the lowest incidence of ILD (incidence rate ratio 0.43; 95% CI 0.18-1.05), followed by abatacept, tocilizumab, and rituximab. Tofacitinib was associated with a significant 69% reduced risk of developing ILD compared with adalimumab (adjusted hazard ratio 0.31; P  =  .009).

Study details: Findings are from a retrospective cohort study including 28,559 patients with RA without preexisting ILD who were newly administered adalimumab, abatacept, rituximab, tocilizumab, or tofacitinib, of which 276 patients were diagnosed with incident ILD.

Disclosures: This study was supported by the US National Institutes of Health and other sources. The authors did not report conflicts of interest.

Source: Baker MC et al. Incidence of interstitial lung disease in patients with rheumatoid arthritis treated with biologic and targeted synthetic disease-modifying antirheumatic drugs. JAMA Netw Open. 2023;6(3):e233640 (Mar 20). Doi: 10.1001/jamanetworkopen.2023.3640

Key clinical point: Patients with rheumatoid arthritis (RA) treated with tofacitinib had a 69% lower risk of developing interstitial lung disease (ILD) than those treated with adalimumab.

Major finding: Compared with adalimumab, tofacitinib resulted in the lowest incidence of ILD (incidence rate ratio 0.43; 95% CI 0.18-1.05), followed by abatacept, tocilizumab, and rituximab. Tofacitinib was associated with a significant 69% reduced risk of developing ILD compared with adalimumab (adjusted hazard ratio 0.31; P  =  .009).

Study details: Findings are from a retrospective cohort study including 28,559 patients with RA without preexisting ILD who were newly administered adalimumab, abatacept, rituximab, tocilizumab, or tofacitinib, of which 276 patients were diagnosed with incident ILD.

Disclosures: This study was supported by the US National Institutes of Health and other sources. The authors did not report conflicts of interest.

Source: Baker MC et al. Incidence of interstitial lung disease in patients with rheumatoid arthritis treated with biologic and targeted synthetic disease-modifying antirheumatic drugs. JAMA Netw Open. 2023;6(3):e233640 (Mar 20). Doi: 10.1001/jamanetworkopen.2023.3640