Article

The sun often is rising in the rearview mirror as I travel with the University of New Mexico dermatology team from Albuquerque to our satellite clinic in Gallup, New Mexico. This twice-monthly trip—with a group usually comprising an attending physician, residents, and medical students—provides an invaluable opportunity for me to take part in delivering care to a majority Native American population and connects our institution and its trainees to the state’s rural and indigenous cultures and communities.

Community outreach is an important initiative for many dermatology residency training programs. Engaging with the community outside the clinic setting allows residents to hone their clinical skills, interact with and meet new people, and help to improve access to health care, especially for members of underserved populations.

Limited access to health care remains a pressing issue in the United States, especially for underserved and rural communities. There currently is no standardized way to measure access to care, but multiple contributing factors have been identified, including but not limited to patient wait times and throughput, provider turnover, ratio of dermatologists to patient population, insurance type, and patient outcomes.¹ Fortunately, there are many ways for dermatology residents to get involved and improve access to dermatologic services in their communities, including skin cancer screenings, free clinics, and teledermatology.

Skin Cancer Screenings

More than 40% of community outreach initiatives offered by dermatology residency programs are related to skin cancer screening and prevention.² The American Academy of Dermatology’s free skin cancer check program (https://www.aad.org/member/career/volunteer/spot) offers a way to participate in or even host a skin cancer screening in your community. Since 1985, this program has identified nearly 300,000 suspicious lesions and more than 30,000 suspected melanomas. Resources for setting up a skin cancer screening in your community are available on the program’s website. Residents may take this opportunity to teach medical students how to perform full-body skin examinations and/or practice making independent decisions as the supervisor for medical trainees. Skin cancer screening events not only expand access to care in underserved communities but also help residents feel more connected to the local community, especially if they have moved to a new location for their residency training.

Free Clinics

Engaging in educational opportunities offered through residency programs is another way to participate in community outreach. In particular, many programs are affiliated with a School of Medicine within their institution that allows residents to spearhead volunteer opportunities such as working at a free clinic. In fact, more than 30% of initiatives offered at dermatology residency programs are free general dermatology clinics.² Residents are in the unique position of being both learners themselves as well as educators to trainees.³ As part of our role, we can provide crucial specialty care to the community by working in concert with medical students and while also familiarizing ourselves with treating populations that we may not reach in our daily clinical work. For example, by participating in free clinics, we can provide care to vulnerable populations who typically may have financial or time barriers that prevent them from seeking care at the institution-associated clinic, including individuals experiencing homelessness, patients who are uninsured, and individuals who cannot take time off work to pursue medical care. Our presence in the community helps to reduce barriers to specialty care, particularly in the field of dermatology where the access shortage in the context of rising skin cancer rates prompts public health concerns.⁴

Teledermatology

Teledermatology became a way to extend our reach in the community more than ever before during the COVID-19 pandemic. Advances in audio, visual, and data telecommunication have been particularly helpful in dermatology, a specialty that relies heavily on visual cues for diagnosis. Synchronous, asynchronous, and hybrid teledermatology services implemented during the pandemic have gained favor among patients and dermatologists and are still applied in current practice.^5,6

For example, in the state of New Mexico (where there is a severe shortage of board-certified dermatologists to care for the state’s population), teledermatology has allowed rural providers of all specialties to consult University of New Mexico dermatologists by sending clinical photographs along with patient information and history via secure messaging. Instead of having the patient travel hundreds of miles to see the nearest dermatologist for their skin condition or endure long wait times to get in to see a specialist, primary providers now can initiate treatment or work-up for their patient’s skin issue in a timely manner with the use of teledermatology to consult specialists.

Teledermatology has demonstrated cost-effectiveness, accuracy, and efficiency in conveniently expanding access to care. It offers patients and dermatologists flexibility in receiving and delivering health care, respectively.⁷ As residents, learning how to navigate this technologic frontier in health care delivery is imperative, as it will remain a prevalent tool in the future care of our communities, particularly in underserved areas.

Final Thoughts

Through community outreach initiatives, dermatology residents have an opportunity not only to enrich our education but also to connect with and become closer to our patients. Skin cancer screenings, free clinics, and teledermatology have provided ways to reach more communities and remain important aspects of dermatology residency.

The sun often is rising in the rearview mirror as I travel with the University of New Mexico dermatology team from Albuquerque to our satellite clinic in Gallup, New Mexico. This twice-monthly trip—with a group usually comprising an attending physician, residents, and medical students—provides an invaluable opportunity for me to take part in delivering care to a majority Native American population and connects our institution and its trainees to the state’s rural and indigenous cultures and communities.

Community outreach is an important initiative for many dermatology residency training programs. Engaging with the community outside the clinic setting allows residents to hone their clinical skills, interact with and meet new people, and help to improve access to health care, especially for members of underserved populations.

Limited access to health care remains a pressing issue in the United States, especially for underserved and rural communities. There currently is no standardized way to measure access to care, but multiple contributing factors have been identified, including but not limited to patient wait times and throughput, provider turnover, ratio of dermatologists to patient population, insurance type, and patient outcomes.¹ Fortunately, there are many ways for dermatology residents to get involved and improve access to dermatologic services in their communities, including skin cancer screenings, free clinics, and teledermatology.

Skin Cancer Screenings

More than 40% of community outreach initiatives offered by dermatology residency programs are related to skin cancer screening and prevention.² The American Academy of Dermatology’s free skin cancer check program (https://www.aad.org/member/career/volunteer/spot) offers a way to participate in or even host a skin cancer screening in your community. Since 1985, this program has identified nearly 300,000 suspicious lesions and more than 30,000 suspected melanomas. Resources for setting up a skin cancer screening in your community are available on the program’s website. Residents may take this opportunity to teach medical students how to perform full-body skin examinations and/or practice making independent decisions as the supervisor for medical trainees. Skin cancer screening events not only expand access to care in underserved communities but also help residents feel more connected to the local community, especially if they have moved to a new location for their residency training.

Free Clinics

Engaging in educational opportunities offered through residency programs is another way to participate in community outreach. In particular, many programs are affiliated with a School of Medicine within their institution that allows residents to spearhead volunteer opportunities such as working at a free clinic. In fact, more than 30% of initiatives offered at dermatology residency programs are free general dermatology clinics.² Residents are in the unique position of being both learners themselves as well as educators to trainees.³ As part of our role, we can provide crucial specialty care to the community by working in concert with medical students and while also familiarizing ourselves with treating populations that we may not reach in our daily clinical work. For example, by participating in free clinics, we can provide care to vulnerable populations who typically may have financial or time barriers that prevent them from seeking care at the institution-associated clinic, including individuals experiencing homelessness, patients who are uninsured, and individuals who cannot take time off work to pursue medical care. Our presence in the community helps to reduce barriers to specialty care, particularly in the field of dermatology where the access shortage in the context of rising skin cancer rates prompts public health concerns.⁴

Teledermatology

Teledermatology became a way to extend our reach in the community more than ever before during the COVID-19 pandemic. Advances in audio, visual, and data telecommunication have been particularly helpful in dermatology, a specialty that relies heavily on visual cues for diagnosis. Synchronous, asynchronous, and hybrid teledermatology services implemented during the pandemic have gained favor among patients and dermatologists and are still applied in current practice.^5,6

For example, in the state of New Mexico (where there is a severe shortage of board-certified dermatologists to care for the state’s population), teledermatology has allowed rural providers of all specialties to consult University of New Mexico dermatologists by sending clinical photographs along with patient information and history via secure messaging. Instead of having the patient travel hundreds of miles to see the nearest dermatologist for their skin condition or endure long wait times to get in to see a specialist, primary providers now can initiate treatment or work-up for their patient’s skin issue in a timely manner with the use of teledermatology to consult specialists.

Teledermatology has demonstrated cost-effectiveness, accuracy, and efficiency in conveniently expanding access to care. It offers patients and dermatologists flexibility in receiving and delivering health care, respectively.⁷ As residents, learning how to navigate this technologic frontier in health care delivery is imperative, as it will remain a prevalent tool in the future care of our communities, particularly in underserved areas.

Final Thoughts

Through community outreach initiatives, dermatology residents have an opportunity not only to enrich our education but also to connect with and become closer to our patients. Skin cancer screenings, free clinics, and teledermatology have provided ways to reach more communities and remain important aspects of dermatology residency.

The sun often is rising in the rearview mirror as I travel with the University of New Mexico dermatology team from Albuquerque to our satellite clinic in Gallup, New Mexico. This twice-monthly trip—with a group usually comprising an attending physician, residents, and medical students—provides an invaluable opportunity for me to take part in delivering care to a majority Native American population and connects our institution and its trainees to the state’s rural and indigenous cultures and communities.

Community outreach is an important initiative for many dermatology residency training programs. Engaging with the community outside the clinic setting allows residents to hone their clinical skills, interact with and meet new people, and help to improve access to health care, especially for members of underserved populations.

Limited access to health care remains a pressing issue in the United States, especially for underserved and rural communities. There currently is no standardized way to measure access to care, but multiple contributing factors have been identified, including but not limited to patient wait times and throughput, provider turnover, ratio of dermatologists to patient population, insurance type, and patient outcomes.¹ Fortunately, there are many ways for dermatology residents to get involved and improve access to dermatologic services in their communities, including skin cancer screenings, free clinics, and teledermatology.

Skin Cancer Screenings

More than 40% of community outreach initiatives offered by dermatology residency programs are related to skin cancer screening and prevention.² The American Academy of Dermatology’s free skin cancer check program (https://www.aad.org/member/career/volunteer/spot) offers a way to participate in or even host a skin cancer screening in your community. Since 1985, this program has identified nearly 300,000 suspicious lesions and more than 30,000 suspected melanomas. Resources for setting up a skin cancer screening in your community are available on the program’s website. Residents may take this opportunity to teach medical students how to perform full-body skin examinations and/or practice making independent decisions as the supervisor for medical trainees. Skin cancer screening events not only expand access to care in underserved communities but also help residents feel more connected to the local community, especially if they have moved to a new location for their residency training.

Free Clinics

Engaging in educational opportunities offered through residency programs is another way to participate in community outreach. In particular, many programs are affiliated with a School of Medicine within their institution that allows residents to spearhead volunteer opportunities such as working at a free clinic. In fact, more than 30% of initiatives offered at dermatology residency programs are free general dermatology clinics.² Residents are in the unique position of being both learners themselves as well as educators to trainees.³ As part of our role, we can provide crucial specialty care to the community by working in concert with medical students and while also familiarizing ourselves with treating populations that we may not reach in our daily clinical work. For example, by participating in free clinics, we can provide care to vulnerable populations who typically may have financial or time barriers that prevent them from seeking care at the institution-associated clinic, including individuals experiencing homelessness, patients who are uninsured, and individuals who cannot take time off work to pursue medical care. Our presence in the community helps to reduce barriers to specialty care, particularly in the field of dermatology where the access shortage in the context of rising skin cancer rates prompts public health concerns.⁴

Teledermatology

Teledermatology became a way to extend our reach in the community more than ever before during the COVID-19 pandemic. Advances in audio, visual, and data telecommunication have been particularly helpful in dermatology, a specialty that relies heavily on visual cues for diagnosis. Synchronous, asynchronous, and hybrid teledermatology services implemented during the pandemic have gained favor among patients and dermatologists and are still applied in current practice.^5,6

For example, in the state of New Mexico (where there is a severe shortage of board-certified dermatologists to care for the state’s population), teledermatology has allowed rural providers of all specialties to consult University of New Mexico dermatologists by sending clinical photographs along with patient information and history via secure messaging. Instead of having the patient travel hundreds of miles to see the nearest dermatologist for their skin condition or endure long wait times to get in to see a specialist, primary providers now can initiate treatment or work-up for their patient’s skin issue in a timely manner with the use of teledermatology to consult specialists.

Teledermatology has demonstrated cost-effectiveness, accuracy, and efficiency in conveniently expanding access to care. It offers patients and dermatologists flexibility in receiving and delivering health care, respectively.⁷ As residents, learning how to navigate this technologic frontier in health care delivery is imperative, as it will remain a prevalent tool in the future care of our communities, particularly in underserved areas.

Final Thoughts

Through community outreach initiatives, dermatology residents have an opportunity not only to enrich our education but also to connect with and become closer to our patients. Skin cancer screenings, free clinics, and teledermatology have provided ways to reach more communities and remain important aspects of dermatology residency.

THE DIAGNOSIS: Chemotherapy-Induced Flagellate Dermatitis

Based on the clinical presentation and temporal relation with chemotherapy, a diagnosis of bleomycininduced flagellate dermatitis (FD) was made, as bleomycin is the only chemotherapeutic agent from this regimen that has been linked with FD.^1,2 Laboratory findings revealed eosinophilia, further supporting a druginduced dermatitis. The patient was treated with oral steroids and diphenhydramine to alleviate itching and discomfort. The chemotherapy was temporarily discontinued until symptomatic improvement was observed within 2 to 3 days.

Flagellate dermatitis is characterized by unique erythematous, linear, intermingled streaks of adjoining firm papules—often preceded by a prodrome of global pruritus—that eventually become hyperpigmented as the erythema subsides. The clinical manifestation of FD can be idiopathic; true/mechanical (dermatitis artefacta, abuse, sadomasochism); chemotherapy induced (peplomycin, trastuzumab, cisplatin, docetaxel, bendamustine); toxin induced (shiitake mushroom, cnidarian stings, Paederus insects); related to rheumatologic diseases (dermatomyositis, adult-onset Still disease), dermatographism, phytophotodermatitis, or poison ivy dermatitis; or induced by chikungunya fever.¹

The term flagellate originates from the Latin word flagellum, which pertains to the distinctive whiplike pattern. It was first described by Moulin et al³ in 1970 in reference to bleomycin-induced linear hyperpigmentation. Bleomycin, a glycopeptide antibiotic derived from Streptomyces verticillus, is used to treat Hodgkin lymphoma, squamous cell carcinoma, and germ cell tumors. The worldwide incidence of bleomycin-induced FD is 8% to 22% and commonly is associated with a cumulative dose greater than 100 U.² Clinical presentation is variable in terms of onset, distribution, and morphology of the eruption and could be independent of dose, route of administration, or type of malignancy being treated. The flagellate rash commonly involves the trunk, arms, and legs; can develop within hours to 6 months of starting bleomycin therapy; often is preceded by generalized itching; and eventually heals with hyperpigmentation.

Possible mechanisms of bleomycin-induced FD include localized melanogenesis, inflammatory pigmentary incontinence, alterations to normal pigmentation patterns, cytotoxic effects of the drug itself, minor trauma/ scratching leading to increased blood flow and causing local accumulation of bleomycin, heat recall, and reduced epidermal turnover leading to extended interaction between keratinocytes and melanocytes.² Heat exposure can act as a trigger for bleomycin-induced skin rash recall even months after the treatment is stopped.

Apart from discontinuing the drug, there is no specific treatment available for bleomycin-induced FD. The primary objective of treatment is to alleviate pruritus, which often involves the use of topical or systemic corticosteroids and oral antihistamines. The duration of treatment depends on the patient’s clinical response. Once treatment is discontinued, FD typically resolves within 6 to 8 months. However, there can be a permanent postinflammatory hyperpigmentation in the affected area.⁴ Although there is a concern for increased mortality after postponement of chemotherapy,⁵ the decision to proceed with or discontinue the chemotherapy regimen necessitates a comprehensive interdisciplinary discussion and a meticulous assessment of the risks and benefits that is customized to each individual patient. Flagellate dermatitis can reoccur with bleomycin re-exposure; a combined approach of proactive topical and systemic steroid treatment seems to diminish the likelihood of FD recurrence.⁵

Our case underscores the importance of recognizing, detecting, and managing FD promptly in individuals undergoing bleomycin-based chemotherapy. Medical professionals should familiarize themselves with this distinct adverse effect linked to bleomycin, enabling prompt discontinuation if necessary, and educate patients about the condition’s typically temporary nature, thereby alleviating their concerns.

THE DIAGNOSIS: Chemotherapy-Induced Flagellate Dermatitis

Based on the clinical presentation and temporal relation with chemotherapy, a diagnosis of bleomycininduced flagellate dermatitis (FD) was made, as bleomycin is the only chemotherapeutic agent from this regimen that has been linked with FD.^1,2 Laboratory findings revealed eosinophilia, further supporting a druginduced dermatitis. The patient was treated with oral steroids and diphenhydramine to alleviate itching and discomfort. The chemotherapy was temporarily discontinued until symptomatic improvement was observed within 2 to 3 days.

Flagellate dermatitis is characterized by unique erythematous, linear, intermingled streaks of adjoining firm papules—often preceded by a prodrome of global pruritus—that eventually become hyperpigmented as the erythema subsides. The clinical manifestation of FD can be idiopathic; true/mechanical (dermatitis artefacta, abuse, sadomasochism); chemotherapy induced (peplomycin, trastuzumab, cisplatin, docetaxel, bendamustine); toxin induced (shiitake mushroom, cnidarian stings, Paederus insects); related to rheumatologic diseases (dermatomyositis, adult-onset Still disease), dermatographism, phytophotodermatitis, or poison ivy dermatitis; or induced by chikungunya fever.¹

The term flagellate originates from the Latin word flagellum, which pertains to the distinctive whiplike pattern. It was first described by Moulin et al³ in 1970 in reference to bleomycin-induced linear hyperpigmentation. Bleomycin, a glycopeptide antibiotic derived from Streptomyces verticillus, is used to treat Hodgkin lymphoma, squamous cell carcinoma, and germ cell tumors. The worldwide incidence of bleomycin-induced FD is 8% to 22% and commonly is associated with a cumulative dose greater than 100 U.² Clinical presentation is variable in terms of onset, distribution, and morphology of the eruption and could be independent of dose, route of administration, or type of malignancy being treated. The flagellate rash commonly involves the trunk, arms, and legs; can develop within hours to 6 months of starting bleomycin therapy; often is preceded by generalized itching; and eventually heals with hyperpigmentation.

Possible mechanisms of bleomycin-induced FD include localized melanogenesis, inflammatory pigmentary incontinence, alterations to normal pigmentation patterns, cytotoxic effects of the drug itself, minor trauma/ scratching leading to increased blood flow and causing local accumulation of bleomycin, heat recall, and reduced epidermal turnover leading to extended interaction between keratinocytes and melanocytes.² Heat exposure can act as a trigger for bleomycin-induced skin rash recall even months after the treatment is stopped.

Apart from discontinuing the drug, there is no specific treatment available for bleomycin-induced FD. The primary objective of treatment is to alleviate pruritus, which often involves the use of topical or systemic corticosteroids and oral antihistamines. The duration of treatment depends on the patient’s clinical response. Once treatment is discontinued, FD typically resolves within 6 to 8 months. However, there can be a permanent postinflammatory hyperpigmentation in the affected area.⁴ Although there is a concern for increased mortality after postponement of chemotherapy,⁵ the decision to proceed with or discontinue the chemotherapy regimen necessitates a comprehensive interdisciplinary discussion and a meticulous assessment of the risks and benefits that is customized to each individual patient. Flagellate dermatitis can reoccur with bleomycin re-exposure; a combined approach of proactive topical and systemic steroid treatment seems to diminish the likelihood of FD recurrence.⁵

Our case underscores the importance of recognizing, detecting, and managing FD promptly in individuals undergoing bleomycin-based chemotherapy. Medical professionals should familiarize themselves with this distinct adverse effect linked to bleomycin, enabling prompt discontinuation if necessary, and educate patients about the condition’s typically temporary nature, thereby alleviating their concerns.

THE DIAGNOSIS: Chemotherapy-Induced Flagellate Dermatitis

Based on the clinical presentation and temporal relation with chemotherapy, a diagnosis of bleomycininduced flagellate dermatitis (FD) was made, as bleomycin is the only chemotherapeutic agent from this regimen that has been linked with FD.^1,2 Laboratory findings revealed eosinophilia, further supporting a druginduced dermatitis. The patient was treated with oral steroids and diphenhydramine to alleviate itching and discomfort. The chemotherapy was temporarily discontinued until symptomatic improvement was observed within 2 to 3 days.

Flagellate dermatitis is characterized by unique erythematous, linear, intermingled streaks of adjoining firm papules—often preceded by a prodrome of global pruritus—that eventually become hyperpigmented as the erythema subsides. The clinical manifestation of FD can be idiopathic; true/mechanical (dermatitis artefacta, abuse, sadomasochism); chemotherapy induced (peplomycin, trastuzumab, cisplatin, docetaxel, bendamustine); toxin induced (shiitake mushroom, cnidarian stings, Paederus insects); related to rheumatologic diseases (dermatomyositis, adult-onset Still disease), dermatographism, phytophotodermatitis, or poison ivy dermatitis; or induced by chikungunya fever.¹

The term flagellate originates from the Latin word flagellum, which pertains to the distinctive whiplike pattern. It was first described by Moulin et al³ in 1970 in reference to bleomycin-induced linear hyperpigmentation. Bleomycin, a glycopeptide antibiotic derived from Streptomyces verticillus, is used to treat Hodgkin lymphoma, squamous cell carcinoma, and germ cell tumors. The worldwide incidence of bleomycin-induced FD is 8% to 22% and commonly is associated with a cumulative dose greater than 100 U.² Clinical presentation is variable in terms of onset, distribution, and morphology of the eruption and could be independent of dose, route of administration, or type of malignancy being treated. The flagellate rash commonly involves the trunk, arms, and legs; can develop within hours to 6 months of starting bleomycin therapy; often is preceded by generalized itching; and eventually heals with hyperpigmentation.

Possible mechanisms of bleomycin-induced FD include localized melanogenesis, inflammatory pigmentary incontinence, alterations to normal pigmentation patterns, cytotoxic effects of the drug itself, minor trauma/ scratching leading to increased blood flow and causing local accumulation of bleomycin, heat recall, and reduced epidermal turnover leading to extended interaction between keratinocytes and melanocytes.² Heat exposure can act as a trigger for bleomycin-induced skin rash recall even months after the treatment is stopped.

Apart from discontinuing the drug, there is no specific treatment available for bleomycin-induced FD. The primary objective of treatment is to alleviate pruritus, which often involves the use of topical or systemic corticosteroids and oral antihistamines. The duration of treatment depends on the patient’s clinical response. Once treatment is discontinued, FD typically resolves within 6 to 8 months. However, there can be a permanent postinflammatory hyperpigmentation in the affected area.⁴ Although there is a concern for increased mortality after postponement of chemotherapy,⁵ the decision to proceed with or discontinue the chemotherapy regimen necessitates a comprehensive interdisciplinary discussion and a meticulous assessment of the risks and benefits that is customized to each individual patient. Flagellate dermatitis can reoccur with bleomycin re-exposure; a combined approach of proactive topical and systemic steroid treatment seems to diminish the likelihood of FD recurrence.⁵

Our case underscores the importance of recognizing, detecting, and managing FD promptly in individuals undergoing bleomycin-based chemotherapy. Medical professionals should familiarize themselves with this distinct adverse effect linked to bleomycin, enabling prompt discontinuation if necessary, and educate patients about the condition’s typically temporary nature, thereby alleviating their concerns.

The Asteraceae (formerly Compositae) family of plants is derived from the ancient Greek word aster, meaning “star,” referring to the starlike arrangement of flower petals around a central disc known as a capitulum. What initially appears as a single flower is actually a composite of several smaller flowers, hence the former name Compositae.¹ Well-known members of the Asteraceae family include ornamental annuals (eg, sunflowers, marigolds, cosmos), herbaceous ­perennials (eg, chrysanthemums, dandelions), vegetables (eg, lettuce, chicory, artichokes), herbs (eg, chamomile, tarragon), and weeds (eg, ragweed, horseweed, capeweed)(Figure 1).²

There are more than 25,000 species of Asteraceae plants that thrive in a wide range of climates worldwide. Cases of Asteraceae-induced skin reactions have been reported in North America, Europe, Asia, and Australia.³ Members of the Asteraceae family are ubiquitous in gardens, along roadsides, and in the wilderness. Occupational exposure commonly affects gardeners, florists, farmers, and forestry workers through either direct contact with plants or via airborne pollen. Furthermore, plants of the Asteraceae family are used in various products, including pediculicides (eg, insect repellents), cosmetics (eg, eye creams, body washes), and food products (eg, cooking oils, sweetening agents, coffee substitutes, herbal teas).^4-6 These plants have substantial allergic potential, resulting in numerous cutaneous reactions.

Allergic Potential

Asteraceae plants can elicit both immediate and delayed hypersensitivity reactions (HSRs); for instance, exposure to ragweed pollen may cause an IgE-mediated type 1 HSR manifesting as allergic rhinitis or a type IV HSR manifesting as airborne allergic contact dermatitis.^7,8 The main contact allergens present in Asteraceae plants are sesquiterpene lactones, which are found in the leaves, stems, flowers, and pollen.^9-11 Sesquiterpene lactones consist of an α-methyl group attached to a lactone ring combined with a sesquiterpene.¹² Patch testing can be used to diagnose Asteraceae allergy; however, the results are not consistently reliable because there is no perfect screening allergen. Patch test preparations commonly used to detect Asteraceae allergy include Compositae mix (consisting of Anthemis nobilis extract, Chamomilla recutita extract, Achillea millefolium extract, Tanacetum vulgare extract, Arnica montana extract, and parthenolide) and sesquiterpene lactone mix (consisting of alantolactone, dehydrocostus lactone, and costunolide). In North America, the prevalence of positive patch tests to Compositae mix and sesquiterpene lactone mix is approximately 2% and 0.5%, respectively.¹³ When patch testing is performed, both Compositae mix and sesquiterpene lactone mix should be utilized to minimize the risk of missing Asteraceae allergy, as sesquiterpene lactone mix alone does not detect all Compositae-sensitized patients. Additionally, it may be necessary to test supplemental Asteraceae allergens, including preparations from specific plants to which the patient has been exposed. Exposure to Asteraceae-containing cosmetic products may lead to dermatitis, though this is highly dependent on the particular plant species involved. For instance, the prevalence of sensitization is high in arnica (tincture) and elecampane but low with more commonly used species such as German chamomile.¹⁴

Cutaneous Manifestations

Asteraceae dermatitis, which also is known as Australian bush dermatitis, weed dermatitis, and chrysanthemum dermatitis,² can manifest on any area of the body that directly contacts the plant or is exposed to the pollen. Asteraceae dermatitis historically was reported in older adults with a recent history of plant exposure.^6,15 However, recent data have shown a female preponderance and a younger mean age of onset (46–49 years).¹⁶

There are multiple distinct clinical manifestations of Asteraceae dermatitis. The most common cutaneous finding is localized vesicular or eczematous patches on the hands or wrists. Other variations include eczematous rashes on the exposed skin of the hands, arms, face, and neck; generalized eczema; and isolated facial eczema.^16,17 These variations can be attributed to contact dermatitis caused by airborne pollen, which may mimic photodermatitis. However, airborne Asteraceae dermatitis can be distinguished clinically from photodermatitis by the involvement of sun-protected areas such as the skinfolds of the eyelids, retroauricular sulci, and nasolabial folds (Figure 2).^2,9 In rare cases, systemic allergic contact dermatitis can occur if the Asteraceae allergen is ingested.^2,18

Management

While complete avoidance of Asteraceae plants is ideal, it often is unrealistic due to their abundance in nature. Therefore, minimizing exposure to the causative plants is recommended. Primary preventive measures such as wearing protective gloves and clothing and applying bentonite clay prior to exposure should be taken when working outdoors. Promptly showering after contact with plants also can reduce the risk for Asteraceae dermatitis.

Symptomatic treatment is appropriate for mild cases and includes topical corticosteroids and calcineurin inhibitors. For severe cases, systemic corticosteroids may be needed for acute flares, with azathioprine, mycophenolate, cyclosporine, or methotrexate available for recalcitrant disease. Verma et al²⁵ found that treatment with azathioprine for 6 months resulted in greater than 60% clearance in all 12 patients, with a majority achieving 80% to 100% clearance. Methotrexate has been used at doses of 15 mg once weekly.²⁶ Narrowband UVB and psoralen plus UVA have been effective in extensive cases; however, care should be exercised in patients with photosensitive dermatitis, who instead should practice strict photoprotection.^27-29 Lakshmi et al³⁰ reported the use of cyclosporine during the acute phase of Asteraceae dermatitis at a dose of 2.5 mg/kg daily for 4 to 8 weeks. There have been several case reports of dupilumab treating allergic contact dermatitis; however, there have been 3 cases of patients with atopic dermatitis developing Asteraceae dermatitis while taking dupilumab.^31,32 Recently, oral Janus kinase inhibitors have shown success in treating refractory cases of airborne Asteraceae dermatitis.^33,34 Further research is needed to determine the safety and efficacy of dupilumab and Janus kinase inhibitors for treatment of Asteraceae dermatitis.

Final Thoughts

The Asteraceae plant family is vast and diverse, with more than 200 species reported to cause allergic contact dermatitis.¹² Common modes of contact include gardening, occupational exposure, airborne pollen, and use of pediculicides and cosmetics that contain components of Asteraceae plants. Educating patients on how to minimize contact with Asteraceae plants is the most effective management strategy; topical agents and oral immunosuppressives can be used for symptomatic treatment.

The Asteraceae (formerly Compositae) family of plants is derived from the ancient Greek word aster, meaning “star,” referring to the starlike arrangement of flower petals around a central disc known as a capitulum. What initially appears as a single flower is actually a composite of several smaller flowers, hence the former name Compositae.¹ Well-known members of the Asteraceae family include ornamental annuals (eg, sunflowers, marigolds, cosmos), herbaceous ­perennials (eg, chrysanthemums, dandelions), vegetables (eg, lettuce, chicory, artichokes), herbs (eg, chamomile, tarragon), and weeds (eg, ragweed, horseweed, capeweed)(Figure 1).²

There are more than 25,000 species of Asteraceae plants that thrive in a wide range of climates worldwide. Cases of Asteraceae-induced skin reactions have been reported in North America, Europe, Asia, and Australia.³ Members of the Asteraceae family are ubiquitous in gardens, along roadsides, and in the wilderness. Occupational exposure commonly affects gardeners, florists, farmers, and forestry workers through either direct contact with plants or via airborne pollen. Furthermore, plants of the Asteraceae family are used in various products, including pediculicides (eg, insect repellents), cosmetics (eg, eye creams, body washes), and food products (eg, cooking oils, sweetening agents, coffee substitutes, herbal teas).^4-6 These plants have substantial allergic potential, resulting in numerous cutaneous reactions.

Allergic Potential

Asteraceae plants can elicit both immediate and delayed hypersensitivity reactions (HSRs); for instance, exposure to ragweed pollen may cause an IgE-mediated type 1 HSR manifesting as allergic rhinitis or a type IV HSR manifesting as airborne allergic contact dermatitis.^7,8 The main contact allergens present in Asteraceae plants are sesquiterpene lactones, which are found in the leaves, stems, flowers, and pollen.^9-11 Sesquiterpene lactones consist of an α-methyl group attached to a lactone ring combined with a sesquiterpene.¹² Patch testing can be used to diagnose Asteraceae allergy; however, the results are not consistently reliable because there is no perfect screening allergen. Patch test preparations commonly used to detect Asteraceae allergy include Compositae mix (consisting of Anthemis nobilis extract, Chamomilla recutita extract, Achillea millefolium extract, Tanacetum vulgare extract, Arnica montana extract, and parthenolide) and sesquiterpene lactone mix (consisting of alantolactone, dehydrocostus lactone, and costunolide). In North America, the prevalence of positive patch tests to Compositae mix and sesquiterpene lactone mix is approximately 2% and 0.5%, respectively.¹³ When patch testing is performed, both Compositae mix and sesquiterpene lactone mix should be utilized to minimize the risk of missing Asteraceae allergy, as sesquiterpene lactone mix alone does not detect all Compositae-sensitized patients. Additionally, it may be necessary to test supplemental Asteraceae allergens, including preparations from specific plants to which the patient has been exposed. Exposure to Asteraceae-containing cosmetic products may lead to dermatitis, though this is highly dependent on the particular plant species involved. For instance, the prevalence of sensitization is high in arnica (tincture) and elecampane but low with more commonly used species such as German chamomile.¹⁴

Cutaneous Manifestations

Asteraceae dermatitis, which also is known as Australian bush dermatitis, weed dermatitis, and chrysanthemum dermatitis,² can manifest on any area of the body that directly contacts the plant or is exposed to the pollen. Asteraceae dermatitis historically was reported in older adults with a recent history of plant exposure.^6,15 However, recent data have shown a female preponderance and a younger mean age of onset (46–49 years).¹⁶

There are multiple distinct clinical manifestations of Asteraceae dermatitis. The most common cutaneous finding is localized vesicular or eczematous patches on the hands or wrists. Other variations include eczematous rashes on the exposed skin of the hands, arms, face, and neck; generalized eczema; and isolated facial eczema.^16,17 These variations can be attributed to contact dermatitis caused by airborne pollen, which may mimic photodermatitis. However, airborne Asteraceae dermatitis can be distinguished clinically from photodermatitis by the involvement of sun-protected areas such as the skinfolds of the eyelids, retroauricular sulci, and nasolabial folds (Figure 2).^2,9 In rare cases, systemic allergic contact dermatitis can occur if the Asteraceae allergen is ingested.^2,18

Management

While complete avoidance of Asteraceae plants is ideal, it often is unrealistic due to their abundance in nature. Therefore, minimizing exposure to the causative plants is recommended. Primary preventive measures such as wearing protective gloves and clothing and applying bentonite clay prior to exposure should be taken when working outdoors. Promptly showering after contact with plants also can reduce the risk for Asteraceae dermatitis.

Symptomatic treatment is appropriate for mild cases and includes topical corticosteroids and calcineurin inhibitors. For severe cases, systemic corticosteroids may be needed for acute flares, with azathioprine, mycophenolate, cyclosporine, or methotrexate available for recalcitrant disease. Verma et al²⁵ found that treatment with azathioprine for 6 months resulted in greater than 60% clearance in all 12 patients, with a majority achieving 80% to 100% clearance. Methotrexate has been used at doses of 15 mg once weekly.²⁶ Narrowband UVB and psoralen plus UVA have been effective in extensive cases; however, care should be exercised in patients with photosensitive dermatitis, who instead should practice strict photoprotection.^27-29 Lakshmi et al³⁰ reported the use of cyclosporine during the acute phase of Asteraceae dermatitis at a dose of 2.5 mg/kg daily for 4 to 8 weeks. There have been several case reports of dupilumab treating allergic contact dermatitis; however, there have been 3 cases of patients with atopic dermatitis developing Asteraceae dermatitis while taking dupilumab.^31,32 Recently, oral Janus kinase inhibitors have shown success in treating refractory cases of airborne Asteraceae dermatitis.^33,34 Further research is needed to determine the safety and efficacy of dupilumab and Janus kinase inhibitors for treatment of Asteraceae dermatitis.

Final Thoughts

The Asteraceae plant family is vast and diverse, with more than 200 species reported to cause allergic contact dermatitis.¹² Common modes of contact include gardening, occupational exposure, airborne pollen, and use of pediculicides and cosmetics that contain components of Asteraceae plants. Educating patients on how to minimize contact with Asteraceae plants is the most effective management strategy; topical agents and oral immunosuppressives can be used for symptomatic treatment.

The Asteraceae (formerly Compositae) family of plants is derived from the ancient Greek word aster, meaning “star,” referring to the starlike arrangement of flower petals around a central disc known as a capitulum. What initially appears as a single flower is actually a composite of several smaller flowers, hence the former name Compositae.¹ Well-known members of the Asteraceae family include ornamental annuals (eg, sunflowers, marigolds, cosmos), herbaceous ­perennials (eg, chrysanthemums, dandelions), vegetables (eg, lettuce, chicory, artichokes), herbs (eg, chamomile, tarragon), and weeds (eg, ragweed, horseweed, capeweed)(Figure 1).²

There are more than 25,000 species of Asteraceae plants that thrive in a wide range of climates worldwide. Cases of Asteraceae-induced skin reactions have been reported in North America, Europe, Asia, and Australia.³ Members of the Asteraceae family are ubiquitous in gardens, along roadsides, and in the wilderness. Occupational exposure commonly affects gardeners, florists, farmers, and forestry workers through either direct contact with plants or via airborne pollen. Furthermore, plants of the Asteraceae family are used in various products, including pediculicides (eg, insect repellents), cosmetics (eg, eye creams, body washes), and food products (eg, cooking oils, sweetening agents, coffee substitutes, herbal teas).^4-6 These plants have substantial allergic potential, resulting in numerous cutaneous reactions.

Allergic Potential

Asteraceae plants can elicit both immediate and delayed hypersensitivity reactions (HSRs); for instance, exposure to ragweed pollen may cause an IgE-mediated type 1 HSR manifesting as allergic rhinitis or a type IV HSR manifesting as airborne allergic contact dermatitis.^7,8 The main contact allergens present in Asteraceae plants are sesquiterpene lactones, which are found in the leaves, stems, flowers, and pollen.^9-11 Sesquiterpene lactones consist of an α-methyl group attached to a lactone ring combined with a sesquiterpene.¹² Patch testing can be used to diagnose Asteraceae allergy; however, the results are not consistently reliable because there is no perfect screening allergen. Patch test preparations commonly used to detect Asteraceae allergy include Compositae mix (consisting of Anthemis nobilis extract, Chamomilla recutita extract, Achillea millefolium extract, Tanacetum vulgare extract, Arnica montana extract, and parthenolide) and sesquiterpene lactone mix (consisting of alantolactone, dehydrocostus lactone, and costunolide). In North America, the prevalence of positive patch tests to Compositae mix and sesquiterpene lactone mix is approximately 2% and 0.5%, respectively.¹³ When patch testing is performed, both Compositae mix and sesquiterpene lactone mix should be utilized to minimize the risk of missing Asteraceae allergy, as sesquiterpene lactone mix alone does not detect all Compositae-sensitized patients. Additionally, it may be necessary to test supplemental Asteraceae allergens, including preparations from specific plants to which the patient has been exposed. Exposure to Asteraceae-containing cosmetic products may lead to dermatitis, though this is highly dependent on the particular plant species involved. For instance, the prevalence of sensitization is high in arnica (tincture) and elecampane but low with more commonly used species such as German chamomile.¹⁴

Cutaneous Manifestations

Asteraceae dermatitis, which also is known as Australian bush dermatitis, weed dermatitis, and chrysanthemum dermatitis,² can manifest on any area of the body that directly contacts the plant or is exposed to the pollen. Asteraceae dermatitis historically was reported in older adults with a recent history of plant exposure.^6,15 However, recent data have shown a female preponderance and a younger mean age of onset (46–49 years).¹⁶

There are multiple distinct clinical manifestations of Asteraceae dermatitis. The most common cutaneous finding is localized vesicular or eczematous patches on the hands or wrists. Other variations include eczematous rashes on the exposed skin of the hands, arms, face, and neck; generalized eczema; and isolated facial eczema.^16,17 These variations can be attributed to contact dermatitis caused by airborne pollen, which may mimic photodermatitis. However, airborne Asteraceae dermatitis can be distinguished clinically from photodermatitis by the involvement of sun-protected areas such as the skinfolds of the eyelids, retroauricular sulci, and nasolabial folds (Figure 2).^2,9 In rare cases, systemic allergic contact dermatitis can occur if the Asteraceae allergen is ingested.^2,18

Management

While complete avoidance of Asteraceae plants is ideal, it often is unrealistic due to their abundance in nature. Therefore, minimizing exposure to the causative plants is recommended. Primary preventive measures such as wearing protective gloves and clothing and applying bentonite clay prior to exposure should be taken when working outdoors. Promptly showering after contact with plants also can reduce the risk for Asteraceae dermatitis.

Symptomatic treatment is appropriate for mild cases and includes topical corticosteroids and calcineurin inhibitors. For severe cases, systemic corticosteroids may be needed for acute flares, with azathioprine, mycophenolate, cyclosporine, or methotrexate available for recalcitrant disease. Verma et al²⁵ found that treatment with azathioprine for 6 months resulted in greater than 60% clearance in all 12 patients, with a majority achieving 80% to 100% clearance. Methotrexate has been used at doses of 15 mg once weekly.²⁶ Narrowband UVB and psoralen plus UVA have been effective in extensive cases; however, care should be exercised in patients with photosensitive dermatitis, who instead should practice strict photoprotection.^27-29 Lakshmi et al³⁰ reported the use of cyclosporine during the acute phase of Asteraceae dermatitis at a dose of 2.5 mg/kg daily for 4 to 8 weeks. There have been several case reports of dupilumab treating allergic contact dermatitis; however, there have been 3 cases of patients with atopic dermatitis developing Asteraceae dermatitis while taking dupilumab.^31,32 Recently, oral Janus kinase inhibitors have shown success in treating refractory cases of airborne Asteraceae dermatitis.^33,34 Further research is needed to determine the safety and efficacy of dupilumab and Janus kinase inhibitors for treatment of Asteraceae dermatitis.

Final Thoughts

The Asteraceae plant family is vast and diverse, with more than 200 species reported to cause allergic contact dermatitis.¹² Common modes of contact include gardening, occupational exposure, airborne pollen, and use of pediculicides and cosmetics that contain components of Asteraceae plants. Educating patients on how to minimize contact with Asteraceae plants is the most effective management strategy; topical agents and oral immunosuppressives can be used for symptomatic treatment.

Hot Topics in Primary Care 2024 is a resource that explores the newest developments in primary care topics that impact your daily clinical practice.

Click on the link below to access the entire supplement. 

• Case Studies in Continuous Glucose Monitoring
• Detection and Diagnosis of Early Symptomatic 
  Alzheimer’s Disease in Primary Care
• Elevating the Importance of Asthma Care in the United States
• Hypercortisolism is More Common Than You Think – 
  Here’s How to Find It
• Improving COPD Management at Transitions of Care
• Improving Patient-Centric COPD Management 
• The Role of Finerenone in Optimizing Cardiovascular-
  Kidney-Metabolic Health: Everything PCPs Should Know
• What Primary Care Clinicians Need to Know About Once-Weekly Insulins

This supplement offers the opportunity to earn a total of 3 continuing medical education (CME) credits. Credit is awarded for the successful completion of the evaluation after reading the article. The links can be found within the supplement on the first page of each article where CME credits are offered.

Click here to read the 2024 Hot Topics in Primary Care

Hot Topics in Primary Care 2024 is a resource that explores the newest developments in primary care topics that impact your daily clinical practice.

Click on the link below to access the entire supplement. 

• Case Studies in Continuous Glucose Monitoring
• Detection and Diagnosis of Early Symptomatic 
  Alzheimer’s Disease in Primary Care
• Elevating the Importance of Asthma Care in the United States
• Hypercortisolism is More Common Than You Think – 
  Here’s How to Find It
• Improving COPD Management at Transitions of Care
• Improving Patient-Centric COPD Management 
• The Role of Finerenone in Optimizing Cardiovascular-
  Kidney-Metabolic Health: Everything PCPs Should Know
• What Primary Care Clinicians Need to Know About Once-Weekly Insulins

This supplement offers the opportunity to earn a total of 3 continuing medical education (CME) credits. Credit is awarded for the successful completion of the evaluation after reading the article. The links can be found within the supplement on the first page of each article where CME credits are offered.

Click here to read the 2024 Hot Topics in Primary Care

Hot Topics in Primary Care 2024 is a resource that explores the newest developments in primary care topics that impact your daily clinical practice.

Click on the link below to access the entire supplement. 

• Case Studies in Continuous Glucose Monitoring
• Detection and Diagnosis of Early Symptomatic 
  Alzheimer’s Disease in Primary Care
• Elevating the Importance of Asthma Care in the United States
• Hypercortisolism is More Common Than You Think – 
  Here’s How to Find It
• Improving COPD Management at Transitions of Care
• Improving Patient-Centric COPD Management 
• The Role of Finerenone in Optimizing Cardiovascular-
  Kidney-Metabolic Health: Everything PCPs Should Know
• What Primary Care Clinicians Need to Know About Once-Weekly Insulins

This supplement offers the opportunity to earn a total of 3 continuing medical education (CME) credits. Credit is awarded for the successful completion of the evaluation after reading the article. The links can be found within the supplement on the first page of each article where CME credits are offered.

Click here to read the 2024 Hot Topics in Primary Care

What is the world’s most dangerous tree? According to Guinness World Records¹ (and one unlucky contestant on the wilderness survival reality show Naked and Afraid,² who got its sap in his eyes and needed to be evacuated for treatment), the manchineel tree (Hippomane mancinella) has earned this designation.^1-3 Manchineel trees are part of the strand vegetation of islands in the West Indies and along the Caribbean coasts of South and Central America, where their copious root systems help reduce coastal erosion. In the United States, this poisonous tree grows along the southern edge of Florida’s Everglades National Park; the Florida Keys; and the US Virgin Islands, especially Virgin Islands National Park. Although the manchineel tree appears on several endangered species lists,^4-6 there are places within its distribution where it is locally abundant and thus poses a risk to residents and visitors.

The first European description of manchineel toxicity was by Peter Martyr d’Anghiera, a court historian and geographer of Christopher Columbus’s patroness, Isabella I, Queen of Castile and Léon. In the early 1500s, Peter Martyr wrote that on Columbus’s second New World voyage in 1493, the crew encountered a mysterious tree that burned the skin and eyes of anyone who had contact with it.⁷ Columbus called the tree’s fruit manzanilla de la muerte (“little apple of death”) after several sailors became severely ill from eating the fruit.^8,9 Manchineel lore is rife with tales of agonizing death after eating the applelike fruit, and several contemporaneous accounts describe indigenous Caribbean islanders using manchineel’s toxic sap as an arrow poison.¹⁰

Eating manchineel fruit is known to cause abdominal pain, burning sensations in the oropharynx, and esophageal spasms.¹¹ Several case reports mention that consuming the fruit can create an exaggerated parasympathomimetic syndrome due to suspected anticholinesteraselike compounds.^3,11,12 Ophthalmologic injuries include severe conjunctivitis—sometimes extensive enough to cause superficial punctate epithelial keratitis.⁵ Dermatologic injuries have been described, but reports on its histopathologic features are limited. We present a case of manchineel dermatitis in a patient who subsequently underwent a skin biopsy.

Case Report

A 64-year-old physician (S.A.N.) came across a stand of manchineel trees while camping in the Virgin Islands National Park on St. John in the US Virgin Islands (Figure 1). The patient—who was knowledgeable about tropical ecology and was familiar with the tree—was curious about its purported cutaneous toxicity and applied the viscous white sap of a broken branchlet (Figure 2) to a patch of skin measuring 4 cm in diameter on the medial left calf. He took serial photographs of the site on days 2, 4 (Figure 3), 6, and 10 (Figure 4), showing the onset of erythema and the subsequent development of follicular pustules. On day 6, a 4-mm punch biopsy specimen was taken of the most prominent pustule. Histopathology showed a subcorneal acantholytic blister and epidermal spongiosis overlying a mixed perivascular infiltrate and follicular necrosis, which was consistent with irritant contact dermatitis (Figure 5). On day 8, the region became indurated and tender to pressure; however, there was no warmth, edema, purulent drainage, lymphangitic streaks, or other signs of infection. The region was never itchy; it was uncomfortable only with firm direct pressure. The patient applied hot compresses to the site for 10 minutes 1 to 2 times daily for roughly 2 weeks, and the affected area healed fully (without any additional intervention) in approximately 6 weeks.

Comment

Manchineel is a member of the Euphorbiaceae (also known as the euphorb or spurge) family, a mainly tropical or subtropical plant family that includes many useful as well as many toxic species. Examples of useful plants include cassava (Manihot esculenta) and the rubber tree (Hevea brasiliensis). Many euphorbs have well-described toxicities, and many (eg, castor bean, Ricinus communis) are useful in some circumstances and toxic in others.^6,12-14 Many euphorbs are known to cause skin reactions, usually due to toxins in the milky sap that directly irritate the skin or to latex compounds that can induce IgE-mediated contact dermatitis.^9,14

Manchineel contains a complex mix of toxins, though no specific one has been identified as the main cause of the associated irritant contact dermatitis. Manchineel sap (and sap of many other euphorbs) contains phorbol esters that may cause direct pH-induced cytotoxicity leading to keratinocyte necrosis. Diterpenes may augment this cytotoxic effect via induction of proinflammatory cytokines.¹² Pitts et al⁵ pointed to a mixture of oxygenated diterpene esters as the primary cause of toxicity and suggested that their water solubility explained occurrences of keratoconjunctivitis after contact with rainwater or dew from the manchineel tree.

All parts of the manchineel tree—fruit, leaves, wood, and sap—are poisonous. In a retrospective series of 97 cases of manchineel fruit ingestion, the most common symptoms were oropharyngeal pain (68% [66/97]), abdominal pain (42% [41/97]), and diarrhea (37% [36/97]). The same series identified 1 (1%) case of bradycardia and hypotension.³ Contact with the wood, exposure to sawdust, and inhalation of smoke from burning the wood can irritate the skin, conjunctivae, or nasopharynx. Rainwater or dew dripping from the leaves onto the skin can cause dermatitis and ophthalmitis, even without direct contact with the tree.^4,5

Management—There is no specific treatment for manchineel dermatitis. Because it is an irritant reaction and not a type IV hypersensitivity reaction, topical corticosteroids have minimal benefit. A regimen consisting of a thorough cleansing, wet compresses, and observation, as most symptoms resolve spontaneously within a few days, has been recommended.⁴ Our patient used hot compresses, which he believes helped heal the site, although his symptoms lasted for several weeks.

Given that there is no specific treatment for manchineel dermatitis, the wisest approach is strict avoidance. On many Caribbean islands, visitors are warned about the manchineel tree, advised to avoid direct contact, and reminded to avoid standing beneath it during a rainstorm (Figure 6).

Conclusion

This article begins with a question: “What is the world’s most dangerous tree?” Many sources from the indexed medical literature as well as the popular press and social media state that it is the manchineel. Although all parts of the manchineel tree are highly toxic, human exposures are uncommon, and deaths are more apocryphal than actual.

What is the world’s most dangerous tree? According to Guinness World Records¹ (and one unlucky contestant on the wilderness survival reality show Naked and Afraid,² who got its sap in his eyes and needed to be evacuated for treatment), the manchineel tree (Hippomane mancinella) has earned this designation.^1-3 Manchineel trees are part of the strand vegetation of islands in the West Indies and along the Caribbean coasts of South and Central America, where their copious root systems help reduce coastal erosion. In the United States, this poisonous tree grows along the southern edge of Florida’s Everglades National Park; the Florida Keys; and the US Virgin Islands, especially Virgin Islands National Park. Although the manchineel tree appears on several endangered species lists,^4-6 there are places within its distribution where it is locally abundant and thus poses a risk to residents and visitors.

The first European description of manchineel toxicity was by Peter Martyr d’Anghiera, a court historian and geographer of Christopher Columbus’s patroness, Isabella I, Queen of Castile and Léon. In the early 1500s, Peter Martyr wrote that on Columbus’s second New World voyage in 1493, the crew encountered a mysterious tree that burned the skin and eyes of anyone who had contact with it.⁷ Columbus called the tree’s fruit manzanilla de la muerte (“little apple of death”) after several sailors became severely ill from eating the fruit.^8,9 Manchineel lore is rife with tales of agonizing death after eating the applelike fruit, and several contemporaneous accounts describe indigenous Caribbean islanders using manchineel’s toxic sap as an arrow poison.¹⁰

Eating manchineel fruit is known to cause abdominal pain, burning sensations in the oropharynx, and esophageal spasms.¹¹ Several case reports mention that consuming the fruit can create an exaggerated parasympathomimetic syndrome due to suspected anticholinesteraselike compounds.^3,11,12 Ophthalmologic injuries include severe conjunctivitis—sometimes extensive enough to cause superficial punctate epithelial keratitis.⁵ Dermatologic injuries have been described, but reports on its histopathologic features are limited. We present a case of manchineel dermatitis in a patient who subsequently underwent a skin biopsy.

Case Report

A 64-year-old physician (S.A.N.) came across a stand of manchineel trees while camping in the Virgin Islands National Park on St. John in the US Virgin Islands (Figure 1). The patient—who was knowledgeable about tropical ecology and was familiar with the tree—was curious about its purported cutaneous toxicity and applied the viscous white sap of a broken branchlet (Figure 2) to a patch of skin measuring 4 cm in diameter on the medial left calf. He took serial photographs of the site on days 2, 4 (Figure 3), 6, and 10 (Figure 4), showing the onset of erythema and the subsequent development of follicular pustules. On day 6, a 4-mm punch biopsy specimen was taken of the most prominent pustule. Histopathology showed a subcorneal acantholytic blister and epidermal spongiosis overlying a mixed perivascular infiltrate and follicular necrosis, which was consistent with irritant contact dermatitis (Figure 5). On day 8, the region became indurated and tender to pressure; however, there was no warmth, edema, purulent drainage, lymphangitic streaks, or other signs of infection. The region was never itchy; it was uncomfortable only with firm direct pressure. The patient applied hot compresses to the site for 10 minutes 1 to 2 times daily for roughly 2 weeks, and the affected area healed fully (without any additional intervention) in approximately 6 weeks.

Comment

Manchineel is a member of the Euphorbiaceae (also known as the euphorb or spurge) family, a mainly tropical or subtropical plant family that includes many useful as well as many toxic species. Examples of useful plants include cassava (Manihot esculenta) and the rubber tree (Hevea brasiliensis). Many euphorbs have well-described toxicities, and many (eg, castor bean, Ricinus communis) are useful in some circumstances and toxic in others.^6,12-14 Many euphorbs are known to cause skin reactions, usually due to toxins in the milky sap that directly irritate the skin or to latex compounds that can induce IgE-mediated contact dermatitis.^9,14

Manchineel contains a complex mix of toxins, though no specific one has been identified as the main cause of the associated irritant contact dermatitis. Manchineel sap (and sap of many other euphorbs) contains phorbol esters that may cause direct pH-induced cytotoxicity leading to keratinocyte necrosis. Diterpenes may augment this cytotoxic effect via induction of proinflammatory cytokines.¹² Pitts et al⁵ pointed to a mixture of oxygenated diterpene esters as the primary cause of toxicity and suggested that their water solubility explained occurrences of keratoconjunctivitis after contact with rainwater or dew from the manchineel tree.

All parts of the manchineel tree—fruit, leaves, wood, and sap—are poisonous. In a retrospective series of 97 cases of manchineel fruit ingestion, the most common symptoms were oropharyngeal pain (68% [66/97]), abdominal pain (42% [41/97]), and diarrhea (37% [36/97]). The same series identified 1 (1%) case of bradycardia and hypotension.³ Contact with the wood, exposure to sawdust, and inhalation of smoke from burning the wood can irritate the skin, conjunctivae, or nasopharynx. Rainwater or dew dripping from the leaves onto the skin can cause dermatitis and ophthalmitis, even without direct contact with the tree.^4,5

Management—There is no specific treatment for manchineel dermatitis. Because it is an irritant reaction and not a type IV hypersensitivity reaction, topical corticosteroids have minimal benefit. A regimen consisting of a thorough cleansing, wet compresses, and observation, as most symptoms resolve spontaneously within a few days, has been recommended.⁴ Our patient used hot compresses, which he believes helped heal the site, although his symptoms lasted for several weeks.

Given that there is no specific treatment for manchineel dermatitis, the wisest approach is strict avoidance. On many Caribbean islands, visitors are warned about the manchineel tree, advised to avoid direct contact, and reminded to avoid standing beneath it during a rainstorm (Figure 6).

Conclusion

This article begins with a question: “What is the world’s most dangerous tree?” Many sources from the indexed medical literature as well as the popular press and social media state that it is the manchineel. Although all parts of the manchineel tree are highly toxic, human exposures are uncommon, and deaths are more apocryphal than actual.

What is the world’s most dangerous tree? According to Guinness World Records¹ (and one unlucky contestant on the wilderness survival reality show Naked and Afraid,² who got its sap in his eyes and needed to be evacuated for treatment), the manchineel tree (Hippomane mancinella) has earned this designation.^1-3 Manchineel trees are part of the strand vegetation of islands in the West Indies and along the Caribbean coasts of South and Central America, where their copious root systems help reduce coastal erosion. In the United States, this poisonous tree grows along the southern edge of Florida’s Everglades National Park; the Florida Keys; and the US Virgin Islands, especially Virgin Islands National Park. Although the manchineel tree appears on several endangered species lists,^4-6 there are places within its distribution where it is locally abundant and thus poses a risk to residents and visitors.

The first European description of manchineel toxicity was by Peter Martyr d’Anghiera, a court historian and geographer of Christopher Columbus’s patroness, Isabella I, Queen of Castile and Léon. In the early 1500s, Peter Martyr wrote that on Columbus’s second New World voyage in 1493, the crew encountered a mysterious tree that burned the skin and eyes of anyone who had contact with it.⁷ Columbus called the tree’s fruit manzanilla de la muerte (“little apple of death”) after several sailors became severely ill from eating the fruit.^8,9 Manchineel lore is rife with tales of agonizing death after eating the applelike fruit, and several contemporaneous accounts describe indigenous Caribbean islanders using manchineel’s toxic sap as an arrow poison.¹⁰

Eating manchineel fruit is known to cause abdominal pain, burning sensations in the oropharynx, and esophageal spasms.¹¹ Several case reports mention that consuming the fruit can create an exaggerated parasympathomimetic syndrome due to suspected anticholinesteraselike compounds.^3,11,12 Ophthalmologic injuries include severe conjunctivitis—sometimes extensive enough to cause superficial punctate epithelial keratitis.⁵ Dermatologic injuries have been described, but reports on its histopathologic features are limited. We present a case of manchineel dermatitis in a patient who subsequently underwent a skin biopsy.

Case Report

A 64-year-old physician (S.A.N.) came across a stand of manchineel trees while camping in the Virgin Islands National Park on St. John in the US Virgin Islands (Figure 1). The patient—who was knowledgeable about tropical ecology and was familiar with the tree—was curious about its purported cutaneous toxicity and applied the viscous white sap of a broken branchlet (Figure 2) to a patch of skin measuring 4 cm in diameter on the medial left calf. He took serial photographs of the site on days 2, 4 (Figure 3), 6, and 10 (Figure 4), showing the onset of erythema and the subsequent development of follicular pustules. On day 6, a 4-mm punch biopsy specimen was taken of the most prominent pustule. Histopathology showed a subcorneal acantholytic blister and epidermal spongiosis overlying a mixed perivascular infiltrate and follicular necrosis, which was consistent with irritant contact dermatitis (Figure 5). On day 8, the region became indurated and tender to pressure; however, there was no warmth, edema, purulent drainage, lymphangitic streaks, or other signs of infection. The region was never itchy; it was uncomfortable only with firm direct pressure. The patient applied hot compresses to the site for 10 minutes 1 to 2 times daily for roughly 2 weeks, and the affected area healed fully (without any additional intervention) in approximately 6 weeks.

Comment

Manchineel is a member of the Euphorbiaceae (also known as the euphorb or spurge) family, a mainly tropical or subtropical plant family that includes many useful as well as many toxic species. Examples of useful plants include cassava (Manihot esculenta) and the rubber tree (Hevea brasiliensis). Many euphorbs have well-described toxicities, and many (eg, castor bean, Ricinus communis) are useful in some circumstances and toxic in others.^6,12-14 Many euphorbs are known to cause skin reactions, usually due to toxins in the milky sap that directly irritate the skin or to latex compounds that can induce IgE-mediated contact dermatitis.^9,14

Manchineel contains a complex mix of toxins, though no specific one has been identified as the main cause of the associated irritant contact dermatitis. Manchineel sap (and sap of many other euphorbs) contains phorbol esters that may cause direct pH-induced cytotoxicity leading to keratinocyte necrosis. Diterpenes may augment this cytotoxic effect via induction of proinflammatory cytokines.¹² Pitts et al⁵ pointed to a mixture of oxygenated diterpene esters as the primary cause of toxicity and suggested that their water solubility explained occurrences of keratoconjunctivitis after contact with rainwater or dew from the manchineel tree.

All parts of the manchineel tree—fruit, leaves, wood, and sap—are poisonous. In a retrospective series of 97 cases of manchineel fruit ingestion, the most common symptoms were oropharyngeal pain (68% [66/97]), abdominal pain (42% [41/97]), and diarrhea (37% [36/97]). The same series identified 1 (1%) case of bradycardia and hypotension.³ Contact with the wood, exposure to sawdust, and inhalation of smoke from burning the wood can irritate the skin, conjunctivae, or nasopharynx. Rainwater or dew dripping from the leaves onto the skin can cause dermatitis and ophthalmitis, even without direct contact with the tree.^4,5

Management—There is no specific treatment for manchineel dermatitis. Because it is an irritant reaction and not a type IV hypersensitivity reaction, topical corticosteroids have minimal benefit. A regimen consisting of a thorough cleansing, wet compresses, and observation, as most symptoms resolve spontaneously within a few days, has been recommended.⁴ Our patient used hot compresses, which he believes helped heal the site, although his symptoms lasted for several weeks.

Given that there is no specific treatment for manchineel dermatitis, the wisest approach is strict avoidance. On many Caribbean islands, visitors are warned about the manchineel tree, advised to avoid direct contact, and reminded to avoid standing beneath it during a rainstorm (Figure 6).

Conclusion

This article begins with a question: “What is the world’s most dangerous tree?” Many sources from the indexed medical literature as well as the popular press and social media state that it is the manchineel. Although all parts of the manchineel tree are highly toxic, human exposures are uncommon, and deaths are more apocryphal than actual.

To the Editor:

Although biologics provide major therapeutic benefits for dermatologic conditions, they also come with a substantial cost, making them among the most expensive medications available. Medicare and Medicaid spending on biologics for dermatologic conditions increased by 320% from 2012 to 2018, reaching a staggering $10.6 billion in 2018 alone.¹ Biosimilars show promise in reducing health care spending for dermatologic conditions; however, their utilization has been limited due to multiple factors, including delayed market entry from patent thickets, exclusionary formulary contracts, and prescriber skepticism regarding their safety and efficacy.² For instance, a national survey of 1201 US physicians in specialties that are high prescribers of biologics reported that 55% doubted the safety and appropriateness of biosimilars.³

US Food and Drug Administration approval of biosimilars for adalimumab and etanercept offers the potential to reduce health care spending for dermatologic conditions. However, this cost reduction is dependent on utilization rates among dermatologists. In this national cross-sectional review of Medicare data, we predicted the impact of these biosimilars on dermatologic Medicare costs and demonstrated how differing utilization rates among dermatologists can influence potential savings.

To model 2023 utilization and cost reduction from biosimilars, we analyzed Medicare Part D data from 2020 on existing biosimilars, including granulocyte colony–stimulating factors, erythropoiesis-stimulating agents, and tumor necrosis factor α inhibitors.⁴ Methods in line with a 2021 report from the US Department of Health and Human Services⁵ as well as those of Yazdany et al⁶ were used. For each class, we calculated the 2020 distribution of biosimilar and originator drug claims as well as biosimilar cost reduction per 30-day claim. We utilized 2018-2021 annual growth rates for branded adalimumab and etanercept to estimate 30-day claims for 2023 and the cost of these branded agents in the absence of biosimilars. The hypothetical 2023 cost reduction from adalimumab and etanercept biosimilars was estimated by assuming 2020 biosimilar utilization rates and mean cost reduction per claim. This study utilized publicly available or aggregate summary data (not attributable to specific patients) and did not qualify as human subject research; therefore, institutional review board approval was not required.

In 2020, biosimilar utilization proportions ranged from 6.4% (tumor necrosis factor α inhibitors) to 82.7% (granulocyte colony–stimulating factors), with a mean across all classes of 35.7%. On average, the cost per 30-day claim of biosimilars was 66.8% of originator agents (Table 1). In 2021, we identified 57,868 30-day claims for branded adalimumab and etanercept submitted by dermatologists. From 2018 to 2021, 30-day branded adalimumab claims increased by 1.27% annually (cost + 10.62% annually), while claims for branded etanercept decreased by 13.0% annually (cost + 5.68% annually). Assuming these trends, the cost of branded adalimumab and etanercept was estimated to be $539 million in 2023. Applying the aforementioned 35.7% utilization, the introduction of biosimilars in dermatology would yield a cost reduction of approximately $118 million (21.9%). A high utilization rate (82.7%) of biosimilars among dermatologists would increase cost savings to $199 million (36.9%)(Table 2).

We found that the extent of savings from biosimilars was dependent on the utilization rates among dermatologists, with the highest utilization rate almost doubling the total savings of average utilization rates. Given the impact of high utilization and the wide variation observed, understanding the factors that have influenced uptake of biosimilars is important to increasing utilization as these medications become integrated into dermatology. For instance, limited uptake of infliximab initially may have been influenced by concerns about efficacy and increased adverse events.^8,9 In contrast, the high utilization of filgrastim biosimilars (82.7%) may be attributed to its longevity in the market and familiarity to prescribers, as filgrastim was the first biosimilar to be approved in the United States.¹⁰

Promoting reasonable utilization of biosimilars may require prescriber education on their safety and approval processes, which could foster increased utilization and reduce skepticism.⁴ Under the Biologics Price Competition and Innovation Act, the US Food and Drug Administration approves biosimilars only when they exhibit “high similarity” and show no “clinically meaningful differences” compared to the reference biologic, with no added safety risks or reduced efficacy.¹¹ Moreover, a 2023 systematic review of 17 studies found no major difference in efficacy and safety between biosimilars and originators of etanercept, infliximab, and other biologics.¹² Understanding these findings may reassure dermatologists and patients about the reliability and safety of biosimilars.

A limitation of our study is that it solely assesses Medicare data and estimates derived from existing (separate) biologic classes. It also does not account for potential expenditure shifts to newer biologic agents (eg, IL-12/17/23 inhibitors) or changes in manufacturer behavior or promotions. Nevertheless, it indicates notable financial savings from new biosimilar agents in dermatology; along with their compelling efficacy and safety profiles, this could represent a substantial benefit to patients and the health care system.

To the Editor:

Although biologics provide major therapeutic benefits for dermatologic conditions, they also come with a substantial cost, making them among the most expensive medications available. Medicare and Medicaid spending on biologics for dermatologic conditions increased by 320% from 2012 to 2018, reaching a staggering $10.6 billion in 2018 alone.¹ Biosimilars show promise in reducing health care spending for dermatologic conditions; however, their utilization has been limited due to multiple factors, including delayed market entry from patent thickets, exclusionary formulary contracts, and prescriber skepticism regarding their safety and efficacy.² For instance, a national survey of 1201 US physicians in specialties that are high prescribers of biologics reported that 55% doubted the safety and appropriateness of biosimilars.³

US Food and Drug Administration approval of biosimilars for adalimumab and etanercept offers the potential to reduce health care spending for dermatologic conditions. However, this cost reduction is dependent on utilization rates among dermatologists. In this national cross-sectional review of Medicare data, we predicted the impact of these biosimilars on dermatologic Medicare costs and demonstrated how differing utilization rates among dermatologists can influence potential savings.

To model 2023 utilization and cost reduction from biosimilars, we analyzed Medicare Part D data from 2020 on existing biosimilars, including granulocyte colony–stimulating factors, erythropoiesis-stimulating agents, and tumor necrosis factor α inhibitors.⁴ Methods in line with a 2021 report from the US Department of Health and Human Services⁵ as well as those of Yazdany et al⁶ were used. For each class, we calculated the 2020 distribution of biosimilar and originator drug claims as well as biosimilar cost reduction per 30-day claim. We utilized 2018-2021 annual growth rates for branded adalimumab and etanercept to estimate 30-day claims for 2023 and the cost of these branded agents in the absence of biosimilars. The hypothetical 2023 cost reduction from adalimumab and etanercept biosimilars was estimated by assuming 2020 biosimilar utilization rates and mean cost reduction per claim. This study utilized publicly available or aggregate summary data (not attributable to specific patients) and did not qualify as human subject research; therefore, institutional review board approval was not required.

In 2020, biosimilar utilization proportions ranged from 6.4% (tumor necrosis factor α inhibitors) to 82.7% (granulocyte colony–stimulating factors), with a mean across all classes of 35.7%. On average, the cost per 30-day claim of biosimilars was 66.8% of originator agents (Table 1). In 2021, we identified 57,868 30-day claims for branded adalimumab and etanercept submitted by dermatologists. From 2018 to 2021, 30-day branded adalimumab claims increased by 1.27% annually (cost + 10.62% annually), while claims for branded etanercept decreased by 13.0% annually (cost + 5.68% annually). Assuming these trends, the cost of branded adalimumab and etanercept was estimated to be $539 million in 2023. Applying the aforementioned 35.7% utilization, the introduction of biosimilars in dermatology would yield a cost reduction of approximately $118 million (21.9%). A high utilization rate (82.7%) of biosimilars among dermatologists would increase cost savings to $199 million (36.9%)(Table 2).

We found that the extent of savings from biosimilars was dependent on the utilization rates among dermatologists, with the highest utilization rate almost doubling the total savings of average utilization rates. Given the impact of high utilization and the wide variation observed, understanding the factors that have influenced uptake of biosimilars is important to increasing utilization as these medications become integrated into dermatology. For instance, limited uptake of infliximab initially may have been influenced by concerns about efficacy and increased adverse events.^8,9 In contrast, the high utilization of filgrastim biosimilars (82.7%) may be attributed to its longevity in the market and familiarity to prescribers, as filgrastim was the first biosimilar to be approved in the United States.¹⁰

Promoting reasonable utilization of biosimilars may require prescriber education on their safety and approval processes, which could foster increased utilization and reduce skepticism.⁴ Under the Biologics Price Competition and Innovation Act, the US Food and Drug Administration approves biosimilars only when they exhibit “high similarity” and show no “clinically meaningful differences” compared to the reference biologic, with no added safety risks or reduced efficacy.¹¹ Moreover, a 2023 systematic review of 17 studies found no major difference in efficacy and safety between biosimilars and originators of etanercept, infliximab, and other biologics.¹² Understanding these findings may reassure dermatologists and patients about the reliability and safety of biosimilars.

A limitation of our study is that it solely assesses Medicare data and estimates derived from existing (separate) biologic classes. It also does not account for potential expenditure shifts to newer biologic agents (eg, IL-12/17/23 inhibitors) or changes in manufacturer behavior or promotions. Nevertheless, it indicates notable financial savings from new biosimilar agents in dermatology; along with their compelling efficacy and safety profiles, this could represent a substantial benefit to patients and the health care system.

To the Editor:

Although biologics provide major therapeutic benefits for dermatologic conditions, they also come with a substantial cost, making them among the most expensive medications available. Medicare and Medicaid spending on biologics for dermatologic conditions increased by 320% from 2012 to 2018, reaching a staggering $10.6 billion in 2018 alone.¹ Biosimilars show promise in reducing health care spending for dermatologic conditions; however, their utilization has been limited due to multiple factors, including delayed market entry from patent thickets, exclusionary formulary contracts, and prescriber skepticism regarding their safety and efficacy.² For instance, a national survey of 1201 US physicians in specialties that are high prescribers of biologics reported that 55% doubted the safety and appropriateness of biosimilars.³

US Food and Drug Administration approval of biosimilars for adalimumab and etanercept offers the potential to reduce health care spending for dermatologic conditions. However, this cost reduction is dependent on utilization rates among dermatologists. In this national cross-sectional review of Medicare data, we predicted the impact of these biosimilars on dermatologic Medicare costs and demonstrated how differing utilization rates among dermatologists can influence potential savings.

To model 2023 utilization and cost reduction from biosimilars, we analyzed Medicare Part D data from 2020 on existing biosimilars, including granulocyte colony–stimulating factors, erythropoiesis-stimulating agents, and tumor necrosis factor α inhibitors.⁴ Methods in line with a 2021 report from the US Department of Health and Human Services⁵ as well as those of Yazdany et al⁶ were used. For each class, we calculated the 2020 distribution of biosimilar and originator drug claims as well as biosimilar cost reduction per 30-day claim. We utilized 2018-2021 annual growth rates for branded adalimumab and etanercept to estimate 30-day claims for 2023 and the cost of these branded agents in the absence of biosimilars. The hypothetical 2023 cost reduction from adalimumab and etanercept biosimilars was estimated by assuming 2020 biosimilar utilization rates and mean cost reduction per claim. This study utilized publicly available or aggregate summary data (not attributable to specific patients) and did not qualify as human subject research; therefore, institutional review board approval was not required.

In 2020, biosimilar utilization proportions ranged from 6.4% (tumor necrosis factor α inhibitors) to 82.7% (granulocyte colony–stimulating factors), with a mean across all classes of 35.7%. On average, the cost per 30-day claim of biosimilars was 66.8% of originator agents (Table 1). In 2021, we identified 57,868 30-day claims for branded adalimumab and etanercept submitted by dermatologists. From 2018 to 2021, 30-day branded adalimumab claims increased by 1.27% annually (cost + 10.62% annually), while claims for branded etanercept decreased by 13.0% annually (cost + 5.68% annually). Assuming these trends, the cost of branded adalimumab and etanercept was estimated to be $539 million in 2023. Applying the aforementioned 35.7% utilization, the introduction of biosimilars in dermatology would yield a cost reduction of approximately $118 million (21.9%). A high utilization rate (82.7%) of biosimilars among dermatologists would increase cost savings to $199 million (36.9%)(Table 2).

We found that the extent of savings from biosimilars was dependent on the utilization rates among dermatologists, with the highest utilization rate almost doubling the total savings of average utilization rates. Given the impact of high utilization and the wide variation observed, understanding the factors that have influenced uptake of biosimilars is important to increasing utilization as these medications become integrated into dermatology. For instance, limited uptake of infliximab initially may have been influenced by concerns about efficacy and increased adverse events.^8,9 In contrast, the high utilization of filgrastim biosimilars (82.7%) may be attributed to its longevity in the market and familiarity to prescribers, as filgrastim was the first biosimilar to be approved in the United States.¹⁰

Promoting reasonable utilization of biosimilars may require prescriber education on their safety and approval processes, which could foster increased utilization and reduce skepticism.⁴ Under the Biologics Price Competition and Innovation Act, the US Food and Drug Administration approves biosimilars only when they exhibit “high similarity” and show no “clinically meaningful differences” compared to the reference biologic, with no added safety risks or reduced efficacy.¹¹ Moreover, a 2023 systematic review of 17 studies found no major difference in efficacy and safety between biosimilars and originators of etanercept, infliximab, and other biologics.¹² Understanding these findings may reassure dermatologists and patients about the reliability and safety of biosimilars.

A limitation of our study is that it solely assesses Medicare data and estimates derived from existing (separate) biologic classes. It also does not account for potential expenditure shifts to newer biologic agents (eg, IL-12/17/23 inhibitors) or changes in manufacturer behavior or promotions. Nevertheless, it indicates notable financial savings from new biosimilar agents in dermatology; along with their compelling efficacy and safety profiles, this could represent a substantial benefit to patients and the health care system.

To the Editor:

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome—a severe cutaneous adverse drug reaction—is characterized by a cutaneous rash and systemic upset in the form of various internal organ and hematologic disturbances. This delayed and idiosyncratic syndrome went by several names, including anticonvulsant hypersensitivity syndrome, before Bocquet et al¹ proposed the term DRESS syndrome.

Phenytoin, a hydantoin derivative used in neurology, was implicated in 41% of cases of DRESS syndrome in a study of 100 patients conducted in southern India.^2,3 While DRESS syndrome is a newer name, the clinical picture of DRESS secondary to phenytoin use remains similar in that it manifests with a morbilliform rash and systemic upset. We sought to describe the clinical and laboratory characteristics of phenytoin-induced DRESS syndrome in this case series.

The analysis included 23 patients with DRESS syndrome secondary to phenytoin use who presented to a tertiary care institution in North India between July 2021 and December 2022, satisfied the European Registry of Severe Cutaneous Adverse Reaction (RegiSCAR) criteria,⁴ and achieved a DRESS diagnostic score of more than 1. The mean age of the patients was 44 years (range, 14–74 years). There was a slight female predominance with a male to female ratio of 0.9:1. More than half of the patients (52.2% [12/23]) presented directly to the dermatology outpatient department; the remaining patients were referred from other departments (47.8% [11/23]). Patients primarily were receiving phenytoin for neurologic indications. Specific reasons included antiseizure prophylaxis following a traffic accident (34.8% [8/23]); epilepsy (26.1% [6/23]); and neoplastic (17.4% [4/23]), vascular (17.4% [4/23]), and infectious (4.3% [1/23]) causes. The mean latency period from drug intake to symptom onset was 29 days (range, 6–62 days), and the mean illness duration was 9 days (range, 1–45 days).

The majority of patients experienced pruritus (91.3% [21/23]) and fever (74.0% [17/23]), and all initially had a rash. Maculopapular morphology was seen in all patients. Erythema multiforme–like (17.4% [4/23]), erythrodermic (17.4% [4/23]), and vesicular (13.0% [3/23]) rashes also were documented (Figure 1). The trunk (100% [23/23]) and extremities (95.7% [22/23]) were involved most often, followed by the palms and soles (56.5% [13/23]). The mean total body surface area affected was 73.65%. Only 7 patients (30.4%) had mucosal ­involvement; nonhemorrhagic cheilitis was the most common manifestation.

To the Editor:

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome—a severe cutaneous adverse drug reaction—is characterized by a cutaneous rash and systemic upset in the form of various internal organ and hematologic disturbances. This delayed and idiosyncratic syndrome went by several names, including anticonvulsant hypersensitivity syndrome, before Bocquet et al¹ proposed the term DRESS syndrome.

Phenytoin, a hydantoin derivative used in neurology, was implicated in 41% of cases of DRESS syndrome in a study of 100 patients conducted in southern India.^2,3 While DRESS syndrome is a newer name, the clinical picture of DRESS secondary to phenytoin use remains similar in that it manifests with a morbilliform rash and systemic upset. We sought to describe the clinical and laboratory characteristics of phenytoin-induced DRESS syndrome in this case series.

The analysis included 23 patients with DRESS syndrome secondary to phenytoin use who presented to a tertiary care institution in North India between July 2021 and December 2022, satisfied the European Registry of Severe Cutaneous Adverse Reaction (RegiSCAR) criteria,⁴ and achieved a DRESS diagnostic score of more than 1. The mean age of the patients was 44 years (range, 14–74 years). There was a slight female predominance with a male to female ratio of 0.9:1. More than half of the patients (52.2% [12/23]) presented directly to the dermatology outpatient department; the remaining patients were referred from other departments (47.8% [11/23]). Patients primarily were receiving phenytoin for neurologic indications. Specific reasons included antiseizure prophylaxis following a traffic accident (34.8% [8/23]); epilepsy (26.1% [6/23]); and neoplastic (17.4% [4/23]), vascular (17.4% [4/23]), and infectious (4.3% [1/23]) causes. The mean latency period from drug intake to symptom onset was 29 days (range, 6–62 days), and the mean illness duration was 9 days (range, 1–45 days).

The majority of patients experienced pruritus (91.3% [21/23]) and fever (74.0% [17/23]), and all initially had a rash. Maculopapular morphology was seen in all patients. Erythema multiforme–like (17.4% [4/23]), erythrodermic (17.4% [4/23]), and vesicular (13.0% [3/23]) rashes also were documented (Figure 1). The trunk (100% [23/23]) and extremities (95.7% [22/23]) were involved most often, followed by the palms and soles (56.5% [13/23]). The mean total body surface area affected was 73.65%. Only 7 patients (30.4%) had mucosal ­involvement; nonhemorrhagic cheilitis was the most common manifestation.

To the Editor:

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome—a severe cutaneous adverse drug reaction—is characterized by a cutaneous rash and systemic upset in the form of various internal organ and hematologic disturbances. This delayed and idiosyncratic syndrome went by several names, including anticonvulsant hypersensitivity syndrome, before Bocquet et al¹ proposed the term DRESS syndrome.

Phenytoin, a hydantoin derivative used in neurology, was implicated in 41% of cases of DRESS syndrome in a study of 100 patients conducted in southern India.^2,3 While DRESS syndrome is a newer name, the clinical picture of DRESS secondary to phenytoin use remains similar in that it manifests with a morbilliform rash and systemic upset. We sought to describe the clinical and laboratory characteristics of phenytoin-induced DRESS syndrome in this case series.

The analysis included 23 patients with DRESS syndrome secondary to phenytoin use who presented to a tertiary care institution in North India between July 2021 and December 2022, satisfied the European Registry of Severe Cutaneous Adverse Reaction (RegiSCAR) criteria,⁴ and achieved a DRESS diagnostic score of more than 1. The mean age of the patients was 44 years (range, 14–74 years). There was a slight female predominance with a male to female ratio of 0.9:1. More than half of the patients (52.2% [12/23]) presented directly to the dermatology outpatient department; the remaining patients were referred from other departments (47.8% [11/23]). Patients primarily were receiving phenytoin for neurologic indications. Specific reasons included antiseizure prophylaxis following a traffic accident (34.8% [8/23]); epilepsy (26.1% [6/23]); and neoplastic (17.4% [4/23]), vascular (17.4% [4/23]), and infectious (4.3% [1/23]) causes. The mean latency period from drug intake to symptom onset was 29 days (range, 6–62 days), and the mean illness duration was 9 days (range, 1–45 days).

The majority of patients experienced pruritus (91.3% [21/23]) and fever (74.0% [17/23]), and all initially had a rash. Maculopapular morphology was seen in all patients. Erythema multiforme–like (17.4% [4/23]), erythrodermic (17.4% [4/23]), and vesicular (13.0% [3/23]) rashes also were documented (Figure 1). The trunk (100% [23/23]) and extremities (95.7% [22/23]) were involved most often, followed by the palms and soles (56.5% [13/23]). The mean total body surface area affected was 73.65%. Only 7 patients (30.4%) had mucosal ­involvement; nonhemorrhagic cheilitis was the most common manifestation.

THE DIAGNOSIS: Ectopic (Accessory) Breast Tissue

Ectopic (accessory) breast tissue (EBT) is a phenomenon caused by failed regression of one or more components of the embryonic mammary ridges— paired ectodermal thickenings that eventually develop into definitive breast tissue including the nipples, areolae, and parenchyma. Ectopic breast tissue is more common in women than men and is believed to be sporadic, although an autosomal-dominant inheritance mechanism with incomplete penetrance has been proposed for some cases.¹ The reported incidence of EBT varies greatly among racial and ethnic groups but is most common in individuals of Asian descent. The incidence across all types of EBT is estimated at 0.25% to 6% in the general population.²

Observed clinical variations of EBT range from simple polythelia (additional nipple[s] without associated parenchyma) to complete polymastia (organized and differentiated accessory breasts). Some types of EBT are rarer than others: One report of gynecologic cancer screenings in 1660 patients found polymastia and polythelia incidences of 0.12% and 5.48%, respectively.³ Of the symptomatic variations, isolated parenchymal EBT without a nipple or areolar complex is the most common and may manifest clinically as unilateral or bilateral tender, mildly erythematous nodules or masses often located in the axillae. Ectopic breast tissue generally is observed along the milk line, a developmental regional designation corresponding to the embryologic mammary ridge and extending linearly from the anterior axilla to the inguinal fold on both sides of the body; however, there have been rare reports of EBT manifesting in areas outside the milk line, such as the face, neck, back, vulva, and extremities.^2,3

Given that the underlying elements of EBT usually are hormone responsive (as with normal breast tissue), the initial symptom onset and subsequent manifestation frequently coincide with pubertal milestones, pregnancy, or lactation. Furthermore, some patients with EBT may experience symptom fluctuations in concordance with monthly menstrual phases. Many cases of EBT are selflimited and resolve within weeks to months after the end of a pregnancy or lactation, but some cases may persist. Continued observation and follow-up are advisable in all patients, as EBT symptoms often recur and the tissue is susceptible to the same disease processes that affect normal breasts, the most concerning of which is malignancy.⁴ Although the true incidence is limited by available data, primary ectopic breast malignancy has been estimated to account for 0.3% to 3.8% of diagnosed breast malignancies.² Cases of malignancy arising from EBT often are of higher grade and poorer prognosis, a finding that may be attributable to diagnostic delays caused by oversight or misdiagnosis of EBT rather than inherent differences in the biologic profile of the tumors.^2,4 Patients with a documented history of EBT may benefit from having their routine breast cancer screenings expanded to include areas with EBT foci.

Potential misdiagnoses for EBT include subcutaneous lipoma, axillary lymphadenopathy, abscess, hidradenitis suppurativa, or malignancy. Features that are suggestive of EBT include symptom association with hormone fluctuations (eg, menstrual phases), absence of fever, and lactescent rather than purulent drainage. Among reported EBT cases, spontaneous lactation rarely is described and, if present, often is associated with a history of prior trauma (eg, core needle biopsy or local abscess formation).⁵ This trauma creates an aberrant connection known as a milk fistula between the underlying parenchyma and the skin surface. Interestingly, our patient denied any history of axillary trauma, but she was noted to be lactating from an apparent milk fistula rather than an organized secretory duct system.

Though a patient history and clinical examination may be sufficient to diagnose EBT cases that are more physically apparent and well correlated with hormone fluctuations, many cases require additional diagnostic studies for confirmation. Of the tools available, ultrasonography generally is considered first-line due to its noninvasive nature, low cost, minimal risk, and high diagnostic value.² Ultrasonography quickly differentiates between abscesses and cystlike processes, which may appear as discrete areas of decreased echogenicity, and breast tissue, which manifests with fibroglandular tissue and lobules of fat.^2,6 Additionally, ultrasonography may demonstrate the secretion of milk through ducts or fistulae, if present. Should examination with ultrasonography prove inconclusive, follow-up studies using conventional radiographic mammography or magnetic resonance imaging may be warranted. Biopsy of EBT foci generally is not indicated unless first-line noninvasive studies fail to yield a conclusive diagnosis; however, biopsy also may be warranted if initial imaging is suggestive of malignancy arising from EBT.²

Management of EBT generally is conservative, and symptoms often resolve without intervention.⁴ Symptomatic relief may be achieved through techniques such as application of warm/cold compresses, avoidance of mechanical stimulation, and use of over-the-counter pain medicine. In cases that are persistent, frequently recurrent, or associated with severe symptoms or that cause considerable cosmetic impact, management with surgical excision and/or liposuction may be warranted.⁷ In our patient, the symptoms were not bothersome enough to warrant surgical intervention, so she was managed conservatively and did not return for follow-up.

THE DIAGNOSIS: Ectopic (Accessory) Breast Tissue

Ectopic (accessory) breast tissue (EBT) is a phenomenon caused by failed regression of one or more components of the embryonic mammary ridges— paired ectodermal thickenings that eventually develop into definitive breast tissue including the nipples, areolae, and parenchyma. Ectopic breast tissue is more common in women than men and is believed to be sporadic, although an autosomal-dominant inheritance mechanism with incomplete penetrance has been proposed for some cases.¹ The reported incidence of EBT varies greatly among racial and ethnic groups but is most common in individuals of Asian descent. The incidence across all types of EBT is estimated at 0.25% to 6% in the general population.²

Observed clinical variations of EBT range from simple polythelia (additional nipple[s] without associated parenchyma) to complete polymastia (organized and differentiated accessory breasts). Some types of EBT are rarer than others: One report of gynecologic cancer screenings in 1660 patients found polymastia and polythelia incidences of 0.12% and 5.48%, respectively.³ Of the symptomatic variations, isolated parenchymal EBT without a nipple or areolar complex is the most common and may manifest clinically as unilateral or bilateral tender, mildly erythematous nodules or masses often located in the axillae. Ectopic breast tissue generally is observed along the milk line, a developmental regional designation corresponding to the embryologic mammary ridge and extending linearly from the anterior axilla to the inguinal fold on both sides of the body; however, there have been rare reports of EBT manifesting in areas outside the milk line, such as the face, neck, back, vulva, and extremities.^2,3

Given that the underlying elements of EBT usually are hormone responsive (as with normal breast tissue), the initial symptom onset and subsequent manifestation frequently coincide with pubertal milestones, pregnancy, or lactation. Furthermore, some patients with EBT may experience symptom fluctuations in concordance with monthly menstrual phases. Many cases of EBT are selflimited and resolve within weeks to months after the end of a pregnancy or lactation, but some cases may persist. Continued observation and follow-up are advisable in all patients, as EBT symptoms often recur and the tissue is susceptible to the same disease processes that affect normal breasts, the most concerning of which is malignancy.⁴ Although the true incidence is limited by available data, primary ectopic breast malignancy has been estimated to account for 0.3% to 3.8% of diagnosed breast malignancies.² Cases of malignancy arising from EBT often are of higher grade and poorer prognosis, a finding that may be attributable to diagnostic delays caused by oversight or misdiagnosis of EBT rather than inherent differences in the biologic profile of the tumors.^2,4 Patients with a documented history of EBT may benefit from having their routine breast cancer screenings expanded to include areas with EBT foci.

Potential misdiagnoses for EBT include subcutaneous lipoma, axillary lymphadenopathy, abscess, hidradenitis suppurativa, or malignancy. Features that are suggestive of EBT include symptom association with hormone fluctuations (eg, menstrual phases), absence of fever, and lactescent rather than purulent drainage. Among reported EBT cases, spontaneous lactation rarely is described and, if present, often is associated with a history of prior trauma (eg, core needle biopsy or local abscess formation).⁵ This trauma creates an aberrant connection known as a milk fistula between the underlying parenchyma and the skin surface. Interestingly, our patient denied any history of axillary trauma, but she was noted to be lactating from an apparent milk fistula rather than an organized secretory duct system.

Though a patient history and clinical examination may be sufficient to diagnose EBT cases that are more physically apparent and well correlated with hormone fluctuations, many cases require additional diagnostic studies for confirmation. Of the tools available, ultrasonography generally is considered first-line due to its noninvasive nature, low cost, minimal risk, and high diagnostic value.² Ultrasonography quickly differentiates between abscesses and cystlike processes, which may appear as discrete areas of decreased echogenicity, and breast tissue, which manifests with fibroglandular tissue and lobules of fat.^2,6 Additionally, ultrasonography may demonstrate the secretion of milk through ducts or fistulae, if present. Should examination with ultrasonography prove inconclusive, follow-up studies using conventional radiographic mammography or magnetic resonance imaging may be warranted. Biopsy of EBT foci generally is not indicated unless first-line noninvasive studies fail to yield a conclusive diagnosis; however, biopsy also may be warranted if initial imaging is suggestive of malignancy arising from EBT.²

Management of EBT generally is conservative, and symptoms often resolve without intervention.⁴ Symptomatic relief may be achieved through techniques such as application of warm/cold compresses, avoidance of mechanical stimulation, and use of over-the-counter pain medicine. In cases that are persistent, frequently recurrent, or associated with severe symptoms or that cause considerable cosmetic impact, management with surgical excision and/or liposuction may be warranted.⁷ In our patient, the symptoms were not bothersome enough to warrant surgical intervention, so she was managed conservatively and did not return for follow-up.

THE DIAGNOSIS: Ectopic (Accessory) Breast Tissue

Ectopic (accessory) breast tissue (EBT) is a phenomenon caused by failed regression of one or more components of the embryonic mammary ridges— paired ectodermal thickenings that eventually develop into definitive breast tissue including the nipples, areolae, and parenchyma. Ectopic breast tissue is more common in women than men and is believed to be sporadic, although an autosomal-dominant inheritance mechanism with incomplete penetrance has been proposed for some cases.¹ The reported incidence of EBT varies greatly among racial and ethnic groups but is most common in individuals of Asian descent. The incidence across all types of EBT is estimated at 0.25% to 6% in the general population.²

Observed clinical variations of EBT range from simple polythelia (additional nipple[s] without associated parenchyma) to complete polymastia (organized and differentiated accessory breasts). Some types of EBT are rarer than others: One report of gynecologic cancer screenings in 1660 patients found polymastia and polythelia incidences of 0.12% and 5.48%, respectively.³ Of the symptomatic variations, isolated parenchymal EBT without a nipple or areolar complex is the most common and may manifest clinically as unilateral or bilateral tender, mildly erythematous nodules or masses often located in the axillae. Ectopic breast tissue generally is observed along the milk line, a developmental regional designation corresponding to the embryologic mammary ridge and extending linearly from the anterior axilla to the inguinal fold on both sides of the body; however, there have been rare reports of EBT manifesting in areas outside the milk line, such as the face, neck, back, vulva, and extremities.^2,3

Given that the underlying elements of EBT usually are hormone responsive (as with normal breast tissue), the initial symptom onset and subsequent manifestation frequently coincide with pubertal milestones, pregnancy, or lactation. Furthermore, some patients with EBT may experience symptom fluctuations in concordance with monthly menstrual phases. Many cases of EBT are selflimited and resolve within weeks to months after the end of a pregnancy or lactation, but some cases may persist. Continued observation and follow-up are advisable in all patients, as EBT symptoms often recur and the tissue is susceptible to the same disease processes that affect normal breasts, the most concerning of which is malignancy.⁴ Although the true incidence is limited by available data, primary ectopic breast malignancy has been estimated to account for 0.3% to 3.8% of diagnosed breast malignancies.² Cases of malignancy arising from EBT often are of higher grade and poorer prognosis, a finding that may be attributable to diagnostic delays caused by oversight or misdiagnosis of EBT rather than inherent differences in the biologic profile of the tumors.^2,4 Patients with a documented history of EBT may benefit from having their routine breast cancer screenings expanded to include areas with EBT foci.

Potential misdiagnoses for EBT include subcutaneous lipoma, axillary lymphadenopathy, abscess, hidradenitis suppurativa, or malignancy. Features that are suggestive of EBT include symptom association with hormone fluctuations (eg, menstrual phases), absence of fever, and lactescent rather than purulent drainage. Among reported EBT cases, spontaneous lactation rarely is described and, if present, often is associated with a history of prior trauma (eg, core needle biopsy or local abscess formation).⁵ This trauma creates an aberrant connection known as a milk fistula between the underlying parenchyma and the skin surface. Interestingly, our patient denied any history of axillary trauma, but she was noted to be lactating from an apparent milk fistula rather than an organized secretory duct system.

Though a patient history and clinical examination may be sufficient to diagnose EBT cases that are more physically apparent and well correlated with hormone fluctuations, many cases require additional diagnostic studies for confirmation. Of the tools available, ultrasonography generally is considered first-line due to its noninvasive nature, low cost, minimal risk, and high diagnostic value.² Ultrasonography quickly differentiates between abscesses and cystlike processes, which may appear as discrete areas of decreased echogenicity, and breast tissue, which manifests with fibroglandular tissue and lobules of fat.^2,6 Additionally, ultrasonography may demonstrate the secretion of milk through ducts or fistulae, if present. Should examination with ultrasonography prove inconclusive, follow-up studies using conventional radiographic mammography or magnetic resonance imaging may be warranted. Biopsy of EBT foci generally is not indicated unless first-line noninvasive studies fail to yield a conclusive diagnosis; however, biopsy also may be warranted if initial imaging is suggestive of malignancy arising from EBT.²

Management of EBT generally is conservative, and symptoms often resolve without intervention.⁴ Symptomatic relief may be achieved through techniques such as application of warm/cold compresses, avoidance of mechanical stimulation, and use of over-the-counter pain medicine. In cases that are persistent, frequently recurrent, or associated with severe symptoms or that cause considerable cosmetic impact, management with surgical excision and/or liposuction may be warranted.⁷ In our patient, the symptoms were not bothersome enough to warrant surgical intervention, so she was managed conservatively and did not return for follow-up.

Key clinical point: The presence of clinical or subclinical dactylitis represented a more active and severe form of psoriatic arthritis (PsA), characterized by increased disease activity, swollen joint counts (SJCs), and tender joint counts (TJCs).

Major finding: PsA with dactylitis (clinical or subclinical) vs without dactylitis was associated with higher median disease activity index in PsA (DAPSA) scores (25.5 vs 16.1; P < .01), SJCs (4 vs 2; P < .001), and TJCs (4 vs 3; P < .01). PsA with subclinical dactylitis vs without dactylitis was associated with even higher DAPSA scores (27.2 vs 16.1; P < .05), SJCs (4.5 vs 2; P < .01), and TJCs (5 vs 3; P < .05).

Study details: This case-control study included 223 patients with PsA who were stratified on the basis of the presence of dactylitis (clinical or subclinical) or its absence at baseline.

Disclosures: This study was supported by the Youth Clinical Research Project of Peking University First Hospital and other sources. No conflicts of interest were reported.

Source: Song Z, Geng Y, Zhang X, Deng X, Zhang Z. Subclinical dactylitis represents a more active phenotype of psoriatic arthritis. Joint Bone Spine. Published online September 24, 2024. Source

Key clinical point: The presence of clinical or subclinical dactylitis represented a more active and severe form of psoriatic arthritis (PsA), characterized by increased disease activity, swollen joint counts (SJCs), and tender joint counts (TJCs).

Major finding: PsA with dactylitis (clinical or subclinical) vs without dactylitis was associated with higher median disease activity index in PsA (DAPSA) scores (25.5 vs 16.1; P < .01), SJCs (4 vs 2; P < .001), and TJCs (4 vs 3; P < .01). PsA with subclinical dactylitis vs without dactylitis was associated with even higher DAPSA scores (27.2 vs 16.1; P < .05), SJCs (4.5 vs 2; P < .01), and TJCs (5 vs 3; P < .05).

Study details: This case-control study included 223 patients with PsA who were stratified on the basis of the presence of dactylitis (clinical or subclinical) or its absence at baseline.

Disclosures: This study was supported by the Youth Clinical Research Project of Peking University First Hospital and other sources. No conflicts of interest were reported.

Source: Song Z, Geng Y, Zhang X, Deng X, Zhang Z. Subclinical dactylitis represents a more active phenotype of psoriatic arthritis. Joint Bone Spine. Published online September 24, 2024. Source

Key clinical point: The presence of clinical or subclinical dactylitis represented a more active and severe form of psoriatic arthritis (PsA), characterized by increased disease activity, swollen joint counts (SJCs), and tender joint counts (TJCs).

Major finding: PsA with dactylitis (clinical or subclinical) vs without dactylitis was associated with higher median disease activity index in PsA (DAPSA) scores (25.5 vs 16.1; P < .01), SJCs (4 vs 2; P < .001), and TJCs (4 vs 3; P < .01). PsA with subclinical dactylitis vs without dactylitis was associated with even higher DAPSA scores (27.2 vs 16.1; P < .05), SJCs (4.5 vs 2; P < .01), and TJCs (5 vs 3; P < .05).

Study details: This case-control study included 223 patients with PsA who were stratified on the basis of the presence of dactylitis (clinical or subclinical) or its absence at baseline.

Disclosures: This study was supported by the Youth Clinical Research Project of Peking University First Hospital and other sources. No conflicts of interest were reported.

Source: Song Z, Geng Y, Zhang X, Deng X, Zhang Z. Subclinical dactylitis represents a more active phenotype of psoriatic arthritis. Joint Bone Spine. Published online September 24, 2024. Source

Key clinical point: Guselkumab administered every 4 weeks (Q4W) or every 8 weeks (Q8W) yielded better clinical outcomes than placebo in patients with psoriatic arthritis (PsA), without any new safety concerns.

Major findings: At week 24, a higher proportion of patients receiving guselkumab Q4W (60%) and Q8W (51%) vs placebo (30%) achieved a ≥ 20% improvement in the American College of Rheumatology (ACR)20 response. The response rates increased through week 52 (69%-78) and were consistent at week 100 (76%-80%) across all the groups. Similar trends were observed for ACR50, with no new safety signals.

Study details: This post hoc analysis of the phase 3 trials DISCOVER-1 and DISCOVER-2 included 1002 biologic-naive patients with PsA who received 100 mg guselkumab Q4W, 100 mg guselkumab at weeks 0 and 4 and then Q8W, or placebo through week 24 with crossover to 100 mg guselkumab Q4W.

Disclosure: The study was sponsored by Janssen-Cilag Ltd. Four authors were employees of Johnson & Johnson. Several authors received research grants, consulting fees, or had ties with various sources.

Source: Mease P, Korotaeva T, Shesternya P, et al. Guselkumab in biologic-naïve patients with active psoriatic arthritis in Russia: A post hoc analysis of the DISCOVER-1 and -2 randomized clinical trials. Rheumatol Ther. Published online September 25, 2024. Source

Key clinical point: Guselkumab administered every 4 weeks (Q4W) or every 8 weeks (Q8W) yielded better clinical outcomes than placebo in patients with psoriatic arthritis (PsA), without any new safety concerns.

Major findings: At week 24, a higher proportion of patients receiving guselkumab Q4W (60%) and Q8W (51%) vs placebo (30%) achieved a ≥ 20% improvement in the American College of Rheumatology (ACR)20 response. The response rates increased through week 52 (69%-78) and were consistent at week 100 (76%-80%) across all the groups. Similar trends were observed for ACR50, with no new safety signals.

Study details: This post hoc analysis of the phase 3 trials DISCOVER-1 and DISCOVER-2 included 1002 biologic-naive patients with PsA who received 100 mg guselkumab Q4W, 100 mg guselkumab at weeks 0 and 4 and then Q8W, or placebo through week 24 with crossover to 100 mg guselkumab Q4W.

Disclosure: The study was sponsored by Janssen-Cilag Ltd. Four authors were employees of Johnson & Johnson. Several authors received research grants, consulting fees, or had ties with various sources.

Source: Mease P, Korotaeva T, Shesternya P, et al. Guselkumab in biologic-naïve patients with active psoriatic arthritis in Russia: A post hoc analysis of the DISCOVER-1 and -2 randomized clinical trials. Rheumatol Ther. Published online September 25, 2024. Source

Key clinical point: Guselkumab administered every 4 weeks (Q4W) or every 8 weeks (Q8W) yielded better clinical outcomes than placebo in patients with psoriatic arthritis (PsA), without any new safety concerns.

Major findings: At week 24, a higher proportion of patients receiving guselkumab Q4W (60%) and Q8W (51%) vs placebo (30%) achieved a ≥ 20% improvement in the American College of Rheumatology (ACR)20 response. The response rates increased through week 52 (69%-78) and were consistent at week 100 (76%-80%) across all the groups. Similar trends were observed for ACR50, with no new safety signals.

Study details: This post hoc analysis of the phase 3 trials DISCOVER-1 and DISCOVER-2 included 1002 biologic-naive patients with PsA who received 100 mg guselkumab Q4W, 100 mg guselkumab at weeks 0 and 4 and then Q8W, or placebo through week 24 with crossover to 100 mg guselkumab Q4W.

Disclosure: The study was sponsored by Janssen-Cilag Ltd. Four authors were employees of Johnson & Johnson. Several authors received research grants, consulting fees, or had ties with various sources.

Source: Mease P, Korotaeva T, Shesternya P, et al. Guselkumab in biologic-naïve patients with active psoriatic arthritis in Russia: A post hoc analysis of the DISCOVER-1 and -2 randomized clinical trials. Rheumatol Ther. Published online September 25, 2024. Source