MDedge Dermatology

Use of artificial intelligence (AI) in dermatology has increased over the past decade, likely driven by advances in deep learning algorithms, computing hardware, and machine learning.¹ Studies comparing the performance of AI algorithms to dermatologists in classifying skin disorders have shown conflicting results.^2,3 In this study, we aimed to analyze AI tools used for diagnosing and classifying skin disease and evaluate the role of dermatologists in the creation of AI technology. We also investigated the number of clinical images used in datasets to train AI programs and compared tools that were created with dermatologist input to those created without dermatologist/clinician involvement.

Methods

A search of PubMed articles indexed for MEDLINE using the terms machine learning, artificial intelligence, and dermatology was conducted on September 18, 2022. Articles were included if they described full-length trials; used machine learning for diagnosis of or screening for dermatologic conditions; and used dermoscopic or gross image datasets of the skin, hair, or nails. Articles were categorized into 4 groups based on the conditions covered: chronic wounds, inflammatory skin diseases, mixed conditions, and pigmented skin lesions. Algorithms were sorted into 4 categories: convolutional/convoluted neural network, deep learning model/deep neural network, AI/artificial neural network, and other. Details regarding Fitzpatrick skin type and skin of color (SoC) inclusion in the articles or AI algorithm datasets were recorded. Univariate and multivariate analyses were performed using Microsoft Excel and SAS Studio 3.8. Sensitivity and specificity were calculated for all included AI technology. Sensitivity, specificity, and the number of clinical images were compared among the included articles using analysis of variance and t tests (α=0.05; P<.05 indicated statistical significance).

Results

Our search yielded 1016 articles, 58 of which met the inclusion criteria. Overall, 25.9% (15/58) of the articles utilized AI to diagnose or classify mixed skin diseases; 22.4% (13/58) for pigmented skin lesions; 19.0% (11/58) for wounds; 17.2% (10/58) for inflammatory skin diseases; and 5.2% (3/58) each for acne, psoriasis, and onychomycosis. Overall, 24.0% (14/58) of articles provided information about Fitzpatrick skin type, and 58.7% (34/58) included clinical images depicting SoC. Furthermore, we found that only 20.7% (12/58) of articles on deep learning models included descriptions of patient ethnicity or race in at least 1 dataset, and only 10.3% (6/58) of studies included any information about skin tone in the dataset. Studies with a dermatologist as the last author (most likely to be supervising the project) were more likely to include clinical images depicting SoC than those without (82.6% [19/23] and 16.7% [3/18], respectively [P=.0411]).

The mean (SD) number of clinical images in the study articles was 28,422 (84,050). Thirty-seven (63.8%) of the study articles included gross images, 17 (29.3%) used dermoscopic images, and 4 (6.9%) used both. Twenty-seven (46.6%) articles used convolutional/convoluted neural networks, 15 (25.9%) used deep learning model/deep neural networks, 8 (13.8%) used other algorithms, 6 (10.3%) used AI/artificial neural network, and 2 (3.4%) used fuzzy algorithms. Most studies were conducted in China (29.3% [17/58]), Germany (12.1% [7/58]), India (10.3% [6/58]), multiple nations (10.3% [6/58]), and the United States (10.3% [6/58]). Overall, 82.8% (48/58) of articles included at least 1 dermatologist coauthor. Sensitivity of the AI models was 0.85, and specificity was 0.85. The average percentage of images in the dataset correctly identified by a physician was 76.87% vs 81.62% of images correctly identified by AI. Average agreement between AI and physician assessment was 77.98%, defined as AI and physician both having the same diagnosis. 

Articles authored by dermatologists contained more clinical images than those without dermatologists in key authorship roles (P<.0001)(eTable). Psoriasis-related algorithms had the fewest (mean [SD]: 3173 [4203]), and pigmented skin lesions had the most clinical images (mean [SD]: 53,19l [155,579]).

Comment

Our results indicated that AI studies with dermatologist authors had significantly more images in their datasets (ie, the set of clinical images of skin lesions used to train AI algorithms in diagnosing or classifying lesions) than those with nondermatologist authors (P<.0001)(eTable). Similarly, in a study of AI technology for skin cancer diagnosis, AI studies with dermatologist authors (ie, included in the development of the AI algorithm) had more images than studies without dermatologist authors.¹ Deep learning textbooks have suggested that 5000 clinical images or training input per output category are needed to produce acceptable algorithm performance, and more than 10 million are needed to produce results superior to human performance.^4-10 Despite advances in AI for dermatologic image analysis, the creation of these models often has been directed by nondermatologists¹; therefore, dermatologist involvement in AI development is necessary to facilitate collection of larger image datasets and optimal performance for image diagnosis/classification tasks.

We found that 20.7% of articles on deep learning models included descriptions of patient ethnicity or race, and only 10.3% of studies included any information about skin tone in the dataset. Furthermore, American investigators primarily trained models using clinical images of patients with lighter skin tones, whereas Chinese investigators exclusively included images depicting darker skin tones. Similarly, in a study of 52 cutaneous imaging deep learning articles, only 17.3% (9/52) reported race and/or Fitzpatrick skin type, and only 7.7% (4/52) of articles included both.^2,6,8 Therefore, dermatologists are needed to contribute images representing diverse populations and collaborate in AI research studies, as their involvement is necessary to ensure the accuracy of AI models in classifying lesions or diagnosing skin lesions across all skin types.

Our search was limited to PubMed, and real-world applications could not be evaluated.

Conclusion

In summary, we found that AI studies with dermatologist authors used larger numbers of clinical images in their datasets and more images representing diverse skin types than studies without. Therefore, we advocate for greater involvement of dermatologists in AI research, which might result in better patient outcomes by improving diagnostic accuracy.

Use of artificial intelligence (AI) in dermatology has increased over the past decade, likely driven by advances in deep learning algorithms, computing hardware, and machine learning.¹ Studies comparing the performance of AI algorithms to dermatologists in classifying skin disorders have shown conflicting results.^2,3 In this study, we aimed to analyze AI tools used for diagnosing and classifying skin disease and evaluate the role of dermatologists in the creation of AI technology. We also investigated the number of clinical images used in datasets to train AI programs and compared tools that were created with dermatologist input to those created without dermatologist/clinician involvement.

Methods

A search of PubMed articles indexed for MEDLINE using the terms machine learning, artificial intelligence, and dermatology was conducted on September 18, 2022. Articles were included if they described full-length trials; used machine learning for diagnosis of or screening for dermatologic conditions; and used dermoscopic or gross image datasets of the skin, hair, or nails. Articles were categorized into 4 groups based on the conditions covered: chronic wounds, inflammatory skin diseases, mixed conditions, and pigmented skin lesions. Algorithms were sorted into 4 categories: convolutional/convoluted neural network, deep learning model/deep neural network, AI/artificial neural network, and other. Details regarding Fitzpatrick skin type and skin of color (SoC) inclusion in the articles or AI algorithm datasets were recorded. Univariate and multivariate analyses were performed using Microsoft Excel and SAS Studio 3.8. Sensitivity and specificity were calculated for all included AI technology. Sensitivity, specificity, and the number of clinical images were compared among the included articles using analysis of variance and t tests (α=0.05; P<.05 indicated statistical significance).

Results

Our search yielded 1016 articles, 58 of which met the inclusion criteria. Overall, 25.9% (15/58) of the articles utilized AI to diagnose or classify mixed skin diseases; 22.4% (13/58) for pigmented skin lesions; 19.0% (11/58) for wounds; 17.2% (10/58) for inflammatory skin diseases; and 5.2% (3/58) each for acne, psoriasis, and onychomycosis. Overall, 24.0% (14/58) of articles provided information about Fitzpatrick skin type, and 58.7% (34/58) included clinical images depicting SoC. Furthermore, we found that only 20.7% (12/58) of articles on deep learning models included descriptions of patient ethnicity or race in at least 1 dataset, and only 10.3% (6/58) of studies included any information about skin tone in the dataset. Studies with a dermatologist as the last author (most likely to be supervising the project) were more likely to include clinical images depicting SoC than those without (82.6% [19/23] and 16.7% [3/18], respectively [P=.0411]).

The mean (SD) number of clinical images in the study articles was 28,422 (84,050). Thirty-seven (63.8%) of the study articles included gross images, 17 (29.3%) used dermoscopic images, and 4 (6.9%) used both. Twenty-seven (46.6%) articles used convolutional/convoluted neural networks, 15 (25.9%) used deep learning model/deep neural networks, 8 (13.8%) used other algorithms, 6 (10.3%) used AI/artificial neural network, and 2 (3.4%) used fuzzy algorithms. Most studies were conducted in China (29.3% [17/58]), Germany (12.1% [7/58]), India (10.3% [6/58]), multiple nations (10.3% [6/58]), and the United States (10.3% [6/58]). Overall, 82.8% (48/58) of articles included at least 1 dermatologist coauthor. Sensitivity of the AI models was 0.85, and specificity was 0.85. The average percentage of images in the dataset correctly identified by a physician was 76.87% vs 81.62% of images correctly identified by AI. Average agreement between AI and physician assessment was 77.98%, defined as AI and physician both having the same diagnosis. 

Articles authored by dermatologists contained more clinical images than those without dermatologists in key authorship roles (P<.0001)(eTable). Psoriasis-related algorithms had the fewest (mean [SD]: 3173 [4203]), and pigmented skin lesions had the most clinical images (mean [SD]: 53,19l [155,579]).

Comment

Our results indicated that AI studies with dermatologist authors had significantly more images in their datasets (ie, the set of clinical images of skin lesions used to train AI algorithms in diagnosing or classifying lesions) than those with nondermatologist authors (P<.0001)(eTable). Similarly, in a study of AI technology for skin cancer diagnosis, AI studies with dermatologist authors (ie, included in the development of the AI algorithm) had more images than studies without dermatologist authors.¹ Deep learning textbooks have suggested that 5000 clinical images or training input per output category are needed to produce acceptable algorithm performance, and more than 10 million are needed to produce results superior to human performance.^4-10 Despite advances in AI for dermatologic image analysis, the creation of these models often has been directed by nondermatologists¹; therefore, dermatologist involvement in AI development is necessary to facilitate collection of larger image datasets and optimal performance for image diagnosis/classification tasks.

We found that 20.7% of articles on deep learning models included descriptions of patient ethnicity or race, and only 10.3% of studies included any information about skin tone in the dataset. Furthermore, American investigators primarily trained models using clinical images of patients with lighter skin tones, whereas Chinese investigators exclusively included images depicting darker skin tones. Similarly, in a study of 52 cutaneous imaging deep learning articles, only 17.3% (9/52) reported race and/or Fitzpatrick skin type, and only 7.7% (4/52) of articles included both.^2,6,8 Therefore, dermatologists are needed to contribute images representing diverse populations and collaborate in AI research studies, as their involvement is necessary to ensure the accuracy of AI models in classifying lesions or diagnosing skin lesions across all skin types.

Our search was limited to PubMed, and real-world applications could not be evaluated.

Conclusion

In summary, we found that AI studies with dermatologist authors used larger numbers of clinical images in their datasets and more images representing diverse skin types than studies without. Therefore, we advocate for greater involvement of dermatologists in AI research, which might result in better patient outcomes by improving diagnostic accuracy.

Use of artificial intelligence (AI) in dermatology has increased over the past decade, likely driven by advances in deep learning algorithms, computing hardware, and machine learning.¹ Studies comparing the performance of AI algorithms to dermatologists in classifying skin disorders have shown conflicting results.^2,3 In this study, we aimed to analyze AI tools used for diagnosing and classifying skin disease and evaluate the role of dermatologists in the creation of AI technology. We also investigated the number of clinical images used in datasets to train AI programs and compared tools that were created with dermatologist input to those created without dermatologist/clinician involvement.

Methods

A search of PubMed articles indexed for MEDLINE using the terms machine learning, artificial intelligence, and dermatology was conducted on September 18, 2022. Articles were included if they described full-length trials; used machine learning for diagnosis of or screening for dermatologic conditions; and used dermoscopic or gross image datasets of the skin, hair, or nails. Articles were categorized into 4 groups based on the conditions covered: chronic wounds, inflammatory skin diseases, mixed conditions, and pigmented skin lesions. Algorithms were sorted into 4 categories: convolutional/convoluted neural network, deep learning model/deep neural network, AI/artificial neural network, and other. Details regarding Fitzpatrick skin type and skin of color (SoC) inclusion in the articles or AI algorithm datasets were recorded. Univariate and multivariate analyses were performed using Microsoft Excel and SAS Studio 3.8. Sensitivity and specificity were calculated for all included AI technology. Sensitivity, specificity, and the number of clinical images were compared among the included articles using analysis of variance and t tests (α=0.05; P<.05 indicated statistical significance).

Results

Our search yielded 1016 articles, 58 of which met the inclusion criteria. Overall, 25.9% (15/58) of the articles utilized AI to diagnose or classify mixed skin diseases; 22.4% (13/58) for pigmented skin lesions; 19.0% (11/58) for wounds; 17.2% (10/58) for inflammatory skin diseases; and 5.2% (3/58) each for acne, psoriasis, and onychomycosis. Overall, 24.0% (14/58) of articles provided information about Fitzpatrick skin type, and 58.7% (34/58) included clinical images depicting SoC. Furthermore, we found that only 20.7% (12/58) of articles on deep learning models included descriptions of patient ethnicity or race in at least 1 dataset, and only 10.3% (6/58) of studies included any information about skin tone in the dataset. Studies with a dermatologist as the last author (most likely to be supervising the project) were more likely to include clinical images depicting SoC than those without (82.6% [19/23] and 16.7% [3/18], respectively [P=.0411]).

The mean (SD) number of clinical images in the study articles was 28,422 (84,050). Thirty-seven (63.8%) of the study articles included gross images, 17 (29.3%) used dermoscopic images, and 4 (6.9%) used both. Twenty-seven (46.6%) articles used convolutional/convoluted neural networks, 15 (25.9%) used deep learning model/deep neural networks, 8 (13.8%) used other algorithms, 6 (10.3%) used AI/artificial neural network, and 2 (3.4%) used fuzzy algorithms. Most studies were conducted in China (29.3% [17/58]), Germany (12.1% [7/58]), India (10.3% [6/58]), multiple nations (10.3% [6/58]), and the United States (10.3% [6/58]). Overall, 82.8% (48/58) of articles included at least 1 dermatologist coauthor. Sensitivity of the AI models was 0.85, and specificity was 0.85. The average percentage of images in the dataset correctly identified by a physician was 76.87% vs 81.62% of images correctly identified by AI. Average agreement between AI and physician assessment was 77.98%, defined as AI and physician both having the same diagnosis. 

Articles authored by dermatologists contained more clinical images than those without dermatologists in key authorship roles (P<.0001)(eTable). Psoriasis-related algorithms had the fewest (mean [SD]: 3173 [4203]), and pigmented skin lesions had the most clinical images (mean [SD]: 53,19l [155,579]).

Comment

Our results indicated that AI studies with dermatologist authors had significantly more images in their datasets (ie, the set of clinical images of skin lesions used to train AI algorithms in diagnosing or classifying lesions) than those with nondermatologist authors (P<.0001)(eTable). Similarly, in a study of AI technology for skin cancer diagnosis, AI studies with dermatologist authors (ie, included in the development of the AI algorithm) had more images than studies without dermatologist authors.¹ Deep learning textbooks have suggested that 5000 clinical images or training input per output category are needed to produce acceptable algorithm performance, and more than 10 million are needed to produce results superior to human performance.^4-10 Despite advances in AI for dermatologic image analysis, the creation of these models often has been directed by nondermatologists¹; therefore, dermatologist involvement in AI development is necessary to facilitate collection of larger image datasets and optimal performance for image diagnosis/classification tasks.

We found that 20.7% of articles on deep learning models included descriptions of patient ethnicity or race, and only 10.3% of studies included any information about skin tone in the dataset. Furthermore, American investigators primarily trained models using clinical images of patients with lighter skin tones, whereas Chinese investigators exclusively included images depicting darker skin tones. Similarly, in a study of 52 cutaneous imaging deep learning articles, only 17.3% (9/52) reported race and/or Fitzpatrick skin type, and only 7.7% (4/52) of articles included both.^2,6,8 Therefore, dermatologists are needed to contribute images representing diverse populations and collaborate in AI research studies, as their involvement is necessary to ensure the accuracy of AI models in classifying lesions or diagnosing skin lesions across all skin types.

Our search was limited to PubMed, and real-world applications could not be evaluated.

Conclusion

In summary, we found that AI studies with dermatologist authors used larger numbers of clinical images in their datasets and more images representing diverse skin types than studies without. Therefore, we advocate for greater involvement of dermatologists in AI research, which might result in better patient outcomes by improving diagnostic accuracy.

Nurse practitioners (NPs) and physician assistants (PAs) often help provide dermatologic care but lack the same mandatory specialized postgraduate training required of board-certified dermatologists (BCDs), which includes at least 3 years of dermatology-focused education in an accredited residency program in addition to an intern year of general medicine, pediatrics, or surgery. Dermatology residency is followed by a certification examination administered by the American Board of Dermatology (ABD) or the American Osteopathic Board of Dermatology, leading to board certification. Some physicians choose to do a fellowship, which typically involves an additional 1 to 2 years of postresidency subspeciality training.

Optional postgraduate dermatology training programs for advanced practice providers (APPs) have been offered by some academic institutions and private practice groups since at least 2003, including Lahey Hospital and Medical Center (Burlington, Massachusetts) as well as the University of Rochester Medical Center (Rochester, New York). Despite a lack of accreditation or standardization, the programs can be beneficial for NPs and PAs to expand their dermatologic knowledge and skills and help bridge the care gap within the specialty. Didactics often are conducted in parallel with the educational activities of the parent institution’s traditional dermatology residency program (eg, lectures, grand rounds). While these programs often are managed by practicing dermatology NPs and PAs, dermatologists also may be involved in their education with didactic instruction, curriculum development, and clinical preceptorship. 

In this cross-sectional study, we identified and evaluated 10 postgraduate dermatology training programs for APPs across the United States. With the growing number of NPs and PAs in the dermatology workforce—both in academic and private practice—it is important for BCDs to be aware of the differences in the dermatology training received in order to ensure safe and effective care is provided through supervisory or collaborative roles (depending on state independent practice laws for APPs and to be aware of the implications these programs may have on the field of dermatology.

Methods

To identify postgraduate dermatology training programs for APPs in the United States, we conducted a cross-sectional study using data obtained via a Google search of various combinations of the following terms: nurse practitioner, NP, physician assistant, PA, advance practice provider, APP, dermatology, postgraduate training, residency, and fellowship. We excluded postgraduate dermatology training programs for APPs that required tuition and did not provide a stipend, as well as programs that lacked the formal structure and credibility needed to qualify as legitimate postgraduate training. Many of the excluded programs operate in a manner that raises ethical concerns, offering pay-to-play opportunities under the guise of education. Information collected on each program included the program name, location, parent institution, program length, class size, curriculum, and any associated salary and benefits.

Results

Ten academic and private practice organizations across the United States that offer postgraduate dermatologic training programs for APPs were identified (eTable). Four (40%) programs were advertised as fellowships. Six (60%) of the programs were offered at academic medical centers, and 4 (40%) were offered by private practices. Most programs were located east of the Mississippi River, and many institutions offered instruction at 1 or more locations within the same state (eFigure). The Advanced Dermatology and Cosmetic Surgery private practice group offered training opportunities in multiple states.

Six programs required APPs to become board-certified NPs or PAs prior to enrolling. Most programs enrolled both NPs and PAs, while some only enrolled NPs (eTable). Only 1 (10%) program required NPs to be board certified as a family NP, while another (10%) recommended that applicants have experience in urgent care, emergency medicine, or trauma medicine. Lahey Hospital & Medical Center required experience as an NP in a general setting for 1 to 2 years prior to applying. No program required prior experience in the field of dermatology.

Program length varied from 6 to 24 months, and cohort size typically was limited to 1 to 2 providers (eTable). Although the exact numbers could not be ascertained, most curricula focused on medical dermatology, including clinical and didactic components, but many offered electives such as cosmetic and procedural dermatology. Two institutions (20%) required independent research. Work typically was limited to 40 hours per week, and most paid a full-time employee salary and provided benefits such as health insurance, retirement, and paid leave (eTable). Kansas Medical Clinic (Topeka, Kansas) required at least 3 years of employment in an underserved community following program completion. The Oasis Dermatology private practice group in Texas required a 1-year teaching commitment after program completion. The Advanced Dermatology and Cosmetic Surgery group offered a full-time position upon program completion.

Comment

There is a large difference in the total number of training and credentialing hours when comparing graduate school training and postgraduate credentialing of medical and osteopathic physicians compared with APPs. A new graduate physician has at least twice as many clinical hours as a PA and 10 times as many clinical hours as an NP prior to starting residency. Physicians also typically complete at least 6 times the number of hours of certification examinations compared to NPs and PAs.¹

Nurse practitioner students typically complete the 500 hours of prelicensure clinical training required for NP school in 2 to 4 years.^2,3 The amount of time required for completion is dependent on the degree and experience of the student upon program entry (eg, bachelor of science in nursing vs master of science in nursing as a terminal degree). Physician assistant students are required to complete 2000 prelicensure clinical hours, and most PA programs are 3 years in duration.⁴ Many NP and PA programs require some degree of clinical experience prior to beginning graduate education.⁵

When comparing prelicensure examinations, questions assessing dermatologic knowledge comprise approximately 6% to 10% of the total questions on the United States Medical Licensing Examination Steps 1 and 2.⁶ The Comprehensive Osteopathic Medical Licensing Examination of the United States Level 1 and Level 2-Cognitive Evaluation both have at least 5% of questions dedicated to dermatology.⁷ Approximately 5% of the questions on the Physician Assistant National Certifying Examination are dedicated to dermatology.⁸ The dermatology content on either of the NP certification examinations is unclear.^2,3 In the states of California, Indiana, and New York, national certification through the American Association of Nurse Practitioners or American Nurses Credentialing Center is not required for NPs to practice in their respective states.⁹

Regarding dermatologic board certification, a new graduate NP may obtain certification from the Dermatology Nurse Practitioner Certification Board with 3000 hours of general dermatology practice that may occur during normal working hours.¹⁰ These hours do not have to occur in one of the previously identified postgraduate APP training programs. The National Board of Dermatology Physician Assistants was founded in 2018 and has since dissolved. The National Board of Dermatology Physician Assistants was not accredited and required at least 3 years of training in dermatology with the same dermatologist in addition to completing a 125-question multiple-choice examination.¹¹ Of note, this examination was opposed by both the ABD and the Society for Dermatology Physician Associates.¹² A PA also may become a Diplomate Fellow with the Society of Dermatology Physician Associates after completion of 64.5 hours of online continuing education modules.⁴ Some PAs may choose to obtain a Certificate of Added Qualifications, which is a voluntary credential that helps document specialty experience and expertise in dermatology or other specialties.

In contrast, a dermatology resident physician requires nearly 11,000 to 13,000 hours of clinical training hours, which last 3 to 4 years following medical school.¹³ This training involves direct patient care under supervision in various settings, including hospitals, outpatient clinics, and surgical procedures. In addition to this clinical experience, dermatology residents must pass a 3-step certification examination process administered by the ABD.¹³ This process includes approximately 20 hours of examinations designed to assess both knowledge and practical skills. For those who wish to further specialize, additional fellowship training in areas such as pediatric dermatology, dermatopathology, or Mohs surgery may follow residency; such fellowships involve an extra 2500 to 3500 hours of training and culminate in another certification examination, further refining a resident’s expertise in a specific dermatologic field. Osteopathic physicians may opt out of the ABD 3-step pathway and obtain board certification through the American Osteopathic Board of Dermatology.¹⁴

Many of the programs we evaluated integrate APP trainees into resident education, allowing participation in equivalent didactic curricula, clinical rotations, and departmental academic activities. The salary and benefits associated with these programs are somewhat like those of resident physicians.^15,16 While most tuition-based programs were excluded from our study due to their lack of credibility and alignment with our study criteria, we identified 2 specific programs that stood out as credible despite requiring students to pay tuition. These programs demonstrated a structured and rigorous curriculum with a clear focus on comprehensive dermatologic training, meeting our standards for inclusion. These programs offer dermatologic training for graduates of NP and PA programs at a cost to the student.^15,16 The program at the Florida Atlantic University, Boca Raton, is largely online,¹⁵ and the program at the University of Miami, Florida, offers no direct clinical contact.¹⁶ These programs illustrate the variety of postgraduate dermatology curricula available nationally in comparison to resident salaries; however, they were not included in our formal analysis because they do not provide structured, in-person clinical training consistent with our inclusion criteria. Neither of these programs would enable participants to qualify for credentialing with the Dermatology Nurse Practitioner Certification Board after completion. While this study identified postgraduate training programs for APPs in dermatology advertised online, it is possible some were omitted or not advertised online.

While many of the postgraduate programs we evaluated provide unique educational opportunities for APPs, it is unknown if graduating providers are equipped to handle the care of patients with complex dermatologic needs. Regardless, the increased utilization of APPs by BCDs has been well documented over the past 2 decades.^17-20 It has been suggested that a higher ratio of APPs to dermatologists can decrease the time it takes for a patient to be seen in a clinic.^21-23 However, investigators have expressed concerns that APPs lack standardized surgical training and clinical hour requirements in the field of dermatology.²⁴ Despite these concerns, Medicare claims data show that APPs are performing advanced surgical and cosmetic procedures at increasing rates.^17,18 Other authors have questioned the cost-effectiveness of APPs, as multiple studies have shown that the number of biopsies needed to diagnose 1 case of skin cancer is higher for midlevel providers than for dermatologists.^25-27

Conclusion

With the anticipated expansion of private equity in dermatology and the growth of our Medicare-eligible population, we are likely to see increased utilization of APPs to address the shortage of BCDs.^28,29 Understanding the prelicensure and postlicensure clinical training requirements, examination hours, and extent of dermatology-focused education among APPs and BCDs can help dermatologists collaborate more effectively and ensure safe, high-quality patient care. Standardizing, improving, and providing high-quality education and promoting lifelong learning in the field of dermatology should be celebrated, and dermatologists are the skin experts best equipped to lead dermatologic education forward.

Nurse practitioners (NPs) and physician assistants (PAs) often help provide dermatologic care but lack the same mandatory specialized postgraduate training required of board-certified dermatologists (BCDs), which includes at least 3 years of dermatology-focused education in an accredited residency program in addition to an intern year of general medicine, pediatrics, or surgery. Dermatology residency is followed by a certification examination administered by the American Board of Dermatology (ABD) or the American Osteopathic Board of Dermatology, leading to board certification. Some physicians choose to do a fellowship, which typically involves an additional 1 to 2 years of postresidency subspeciality training.

Optional postgraduate dermatology training programs for advanced practice providers (APPs) have been offered by some academic institutions and private practice groups since at least 2003, including Lahey Hospital and Medical Center (Burlington, Massachusetts) as well as the University of Rochester Medical Center (Rochester, New York). Despite a lack of accreditation or standardization, the programs can be beneficial for NPs and PAs to expand their dermatologic knowledge and skills and help bridge the care gap within the specialty. Didactics often are conducted in parallel with the educational activities of the parent institution’s traditional dermatology residency program (eg, lectures, grand rounds). While these programs often are managed by practicing dermatology NPs and PAs, dermatologists also may be involved in their education with didactic instruction, curriculum development, and clinical preceptorship. 

In this cross-sectional study, we identified and evaluated 10 postgraduate dermatology training programs for APPs across the United States. With the growing number of NPs and PAs in the dermatology workforce—both in academic and private practice—it is important for BCDs to be aware of the differences in the dermatology training received in order to ensure safe and effective care is provided through supervisory or collaborative roles (depending on state independent practice laws for APPs and to be aware of the implications these programs may have on the field of dermatology.

Methods

To identify postgraduate dermatology training programs for APPs in the United States, we conducted a cross-sectional study using data obtained via a Google search of various combinations of the following terms: nurse practitioner, NP, physician assistant, PA, advance practice provider, APP, dermatology, postgraduate training, residency, and fellowship. We excluded postgraduate dermatology training programs for APPs that required tuition and did not provide a stipend, as well as programs that lacked the formal structure and credibility needed to qualify as legitimate postgraduate training. Many of the excluded programs operate in a manner that raises ethical concerns, offering pay-to-play opportunities under the guise of education. Information collected on each program included the program name, location, parent institution, program length, class size, curriculum, and any associated salary and benefits.

Results

Ten academic and private practice organizations across the United States that offer postgraduate dermatologic training programs for APPs were identified (eTable). Four (40%) programs were advertised as fellowships. Six (60%) of the programs were offered at academic medical centers, and 4 (40%) were offered by private practices. Most programs were located east of the Mississippi River, and many institutions offered instruction at 1 or more locations within the same state (eFigure). The Advanced Dermatology and Cosmetic Surgery private practice group offered training opportunities in multiple states.

Six programs required APPs to become board-certified NPs or PAs prior to enrolling. Most programs enrolled both NPs and PAs, while some only enrolled NPs (eTable). Only 1 (10%) program required NPs to be board certified as a family NP, while another (10%) recommended that applicants have experience in urgent care, emergency medicine, or trauma medicine. Lahey Hospital & Medical Center required experience as an NP in a general setting for 1 to 2 years prior to applying. No program required prior experience in the field of dermatology.

Program length varied from 6 to 24 months, and cohort size typically was limited to 1 to 2 providers (eTable). Although the exact numbers could not be ascertained, most curricula focused on medical dermatology, including clinical and didactic components, but many offered electives such as cosmetic and procedural dermatology. Two institutions (20%) required independent research. Work typically was limited to 40 hours per week, and most paid a full-time employee salary and provided benefits such as health insurance, retirement, and paid leave (eTable). Kansas Medical Clinic (Topeka, Kansas) required at least 3 years of employment in an underserved community following program completion. The Oasis Dermatology private practice group in Texas required a 1-year teaching commitment after program completion. The Advanced Dermatology and Cosmetic Surgery group offered a full-time position upon program completion.

Comment

There is a large difference in the total number of training and credentialing hours when comparing graduate school training and postgraduate credentialing of medical and osteopathic physicians compared with APPs. A new graduate physician has at least twice as many clinical hours as a PA and 10 times as many clinical hours as an NP prior to starting residency. Physicians also typically complete at least 6 times the number of hours of certification examinations compared to NPs and PAs.¹

Nurse practitioner students typically complete the 500 hours of prelicensure clinical training required for NP school in 2 to 4 years.^2,3 The amount of time required for completion is dependent on the degree and experience of the student upon program entry (eg, bachelor of science in nursing vs master of science in nursing as a terminal degree). Physician assistant students are required to complete 2000 prelicensure clinical hours, and most PA programs are 3 years in duration.⁴ Many NP and PA programs require some degree of clinical experience prior to beginning graduate education.⁵

When comparing prelicensure examinations, questions assessing dermatologic knowledge comprise approximately 6% to 10% of the total questions on the United States Medical Licensing Examination Steps 1 and 2.⁶ The Comprehensive Osteopathic Medical Licensing Examination of the United States Level 1 and Level 2-Cognitive Evaluation both have at least 5% of questions dedicated to dermatology.⁷ Approximately 5% of the questions on the Physician Assistant National Certifying Examination are dedicated to dermatology.⁸ The dermatology content on either of the NP certification examinations is unclear.^2,3 In the states of California, Indiana, and New York, national certification through the American Association of Nurse Practitioners or American Nurses Credentialing Center is not required for NPs to practice in their respective states.⁹

Regarding dermatologic board certification, a new graduate NP may obtain certification from the Dermatology Nurse Practitioner Certification Board with 3000 hours of general dermatology practice that may occur during normal working hours.¹⁰ These hours do not have to occur in one of the previously identified postgraduate APP training programs. The National Board of Dermatology Physician Assistants was founded in 2018 and has since dissolved. The National Board of Dermatology Physician Assistants was not accredited and required at least 3 years of training in dermatology with the same dermatologist in addition to completing a 125-question multiple-choice examination.¹¹ Of note, this examination was opposed by both the ABD and the Society for Dermatology Physician Associates.¹² A PA also may become a Diplomate Fellow with the Society of Dermatology Physician Associates after completion of 64.5 hours of online continuing education modules.⁴ Some PAs may choose to obtain a Certificate of Added Qualifications, which is a voluntary credential that helps document specialty experience and expertise in dermatology or other specialties.

In contrast, a dermatology resident physician requires nearly 11,000 to 13,000 hours of clinical training hours, which last 3 to 4 years following medical school.¹³ This training involves direct patient care under supervision in various settings, including hospitals, outpatient clinics, and surgical procedures. In addition to this clinical experience, dermatology residents must pass a 3-step certification examination process administered by the ABD.¹³ This process includes approximately 20 hours of examinations designed to assess both knowledge and practical skills. For those who wish to further specialize, additional fellowship training in areas such as pediatric dermatology, dermatopathology, or Mohs surgery may follow residency; such fellowships involve an extra 2500 to 3500 hours of training and culminate in another certification examination, further refining a resident’s expertise in a specific dermatologic field. Osteopathic physicians may opt out of the ABD 3-step pathway and obtain board certification through the American Osteopathic Board of Dermatology.¹⁴

Many of the programs we evaluated integrate APP trainees into resident education, allowing participation in equivalent didactic curricula, clinical rotations, and departmental academic activities. The salary and benefits associated with these programs are somewhat like those of resident physicians.^15,16 While most tuition-based programs were excluded from our study due to their lack of credibility and alignment with our study criteria, we identified 2 specific programs that stood out as credible despite requiring students to pay tuition. These programs demonstrated a structured and rigorous curriculum with a clear focus on comprehensive dermatologic training, meeting our standards for inclusion. These programs offer dermatologic training for graduates of NP and PA programs at a cost to the student.^15,16 The program at the Florida Atlantic University, Boca Raton, is largely online,¹⁵ and the program at the University of Miami, Florida, offers no direct clinical contact.¹⁶ These programs illustrate the variety of postgraduate dermatology curricula available nationally in comparison to resident salaries; however, they were not included in our formal analysis because they do not provide structured, in-person clinical training consistent with our inclusion criteria. Neither of these programs would enable participants to qualify for credentialing with the Dermatology Nurse Practitioner Certification Board after completion. While this study identified postgraduate training programs for APPs in dermatology advertised online, it is possible some were omitted or not advertised online.

While many of the postgraduate programs we evaluated provide unique educational opportunities for APPs, it is unknown if graduating providers are equipped to handle the care of patients with complex dermatologic needs. Regardless, the increased utilization of APPs by BCDs has been well documented over the past 2 decades.^17-20 It has been suggested that a higher ratio of APPs to dermatologists can decrease the time it takes for a patient to be seen in a clinic.^21-23 However, investigators have expressed concerns that APPs lack standardized surgical training and clinical hour requirements in the field of dermatology.²⁴ Despite these concerns, Medicare claims data show that APPs are performing advanced surgical and cosmetic procedures at increasing rates.^17,18 Other authors have questioned the cost-effectiveness of APPs, as multiple studies have shown that the number of biopsies needed to diagnose 1 case of skin cancer is higher for midlevel providers than for dermatologists.^25-27

Conclusion

With the anticipated expansion of private equity in dermatology and the growth of our Medicare-eligible population, we are likely to see increased utilization of APPs to address the shortage of BCDs.^28,29 Understanding the prelicensure and postlicensure clinical training requirements, examination hours, and extent of dermatology-focused education among APPs and BCDs can help dermatologists collaborate more effectively and ensure safe, high-quality patient care. Standardizing, improving, and providing high-quality education and promoting lifelong learning in the field of dermatology should be celebrated, and dermatologists are the skin experts best equipped to lead dermatologic education forward.

Nurse practitioners (NPs) and physician assistants (PAs) often help provide dermatologic care but lack the same mandatory specialized postgraduate training required of board-certified dermatologists (BCDs), which includes at least 3 years of dermatology-focused education in an accredited residency program in addition to an intern year of general medicine, pediatrics, or surgery. Dermatology residency is followed by a certification examination administered by the American Board of Dermatology (ABD) or the American Osteopathic Board of Dermatology, leading to board certification. Some physicians choose to do a fellowship, which typically involves an additional 1 to 2 years of postresidency subspeciality training.

Optional postgraduate dermatology training programs for advanced practice providers (APPs) have been offered by some academic institutions and private practice groups since at least 2003, including Lahey Hospital and Medical Center (Burlington, Massachusetts) as well as the University of Rochester Medical Center (Rochester, New York). Despite a lack of accreditation or standardization, the programs can be beneficial for NPs and PAs to expand their dermatologic knowledge and skills and help bridge the care gap within the specialty. Didactics often are conducted in parallel with the educational activities of the parent institution’s traditional dermatology residency program (eg, lectures, grand rounds). While these programs often are managed by practicing dermatology NPs and PAs, dermatologists also may be involved in their education with didactic instruction, curriculum development, and clinical preceptorship. 

In this cross-sectional study, we identified and evaluated 10 postgraduate dermatology training programs for APPs across the United States. With the growing number of NPs and PAs in the dermatology workforce—both in academic and private practice—it is important for BCDs to be aware of the differences in the dermatology training received in order to ensure safe and effective care is provided through supervisory or collaborative roles (depending on state independent practice laws for APPs and to be aware of the implications these programs may have on the field of dermatology.

Methods

To identify postgraduate dermatology training programs for APPs in the United States, we conducted a cross-sectional study using data obtained via a Google search of various combinations of the following terms: nurse practitioner, NP, physician assistant, PA, advance practice provider, APP, dermatology, postgraduate training, residency, and fellowship. We excluded postgraduate dermatology training programs for APPs that required tuition and did not provide a stipend, as well as programs that lacked the formal structure and credibility needed to qualify as legitimate postgraduate training. Many of the excluded programs operate in a manner that raises ethical concerns, offering pay-to-play opportunities under the guise of education. Information collected on each program included the program name, location, parent institution, program length, class size, curriculum, and any associated salary and benefits.

Results

Ten academic and private practice organizations across the United States that offer postgraduate dermatologic training programs for APPs were identified (eTable). Four (40%) programs were advertised as fellowships. Six (60%) of the programs were offered at academic medical centers, and 4 (40%) were offered by private practices. Most programs were located east of the Mississippi River, and many institutions offered instruction at 1 or more locations within the same state (eFigure). The Advanced Dermatology and Cosmetic Surgery private practice group offered training opportunities in multiple states.

Six programs required APPs to become board-certified NPs or PAs prior to enrolling. Most programs enrolled both NPs and PAs, while some only enrolled NPs (eTable). Only 1 (10%) program required NPs to be board certified as a family NP, while another (10%) recommended that applicants have experience in urgent care, emergency medicine, or trauma medicine. Lahey Hospital & Medical Center required experience as an NP in a general setting for 1 to 2 years prior to applying. No program required prior experience in the field of dermatology.

Program length varied from 6 to 24 months, and cohort size typically was limited to 1 to 2 providers (eTable). Although the exact numbers could not be ascertained, most curricula focused on medical dermatology, including clinical and didactic components, but many offered electives such as cosmetic and procedural dermatology. Two institutions (20%) required independent research. Work typically was limited to 40 hours per week, and most paid a full-time employee salary and provided benefits such as health insurance, retirement, and paid leave (eTable). Kansas Medical Clinic (Topeka, Kansas) required at least 3 years of employment in an underserved community following program completion. The Oasis Dermatology private practice group in Texas required a 1-year teaching commitment after program completion. The Advanced Dermatology and Cosmetic Surgery group offered a full-time position upon program completion.

Comment

There is a large difference in the total number of training and credentialing hours when comparing graduate school training and postgraduate credentialing of medical and osteopathic physicians compared with APPs. A new graduate physician has at least twice as many clinical hours as a PA and 10 times as many clinical hours as an NP prior to starting residency. Physicians also typically complete at least 6 times the number of hours of certification examinations compared to NPs and PAs.¹

Nurse practitioner students typically complete the 500 hours of prelicensure clinical training required for NP school in 2 to 4 years.^2,3 The amount of time required for completion is dependent on the degree and experience of the student upon program entry (eg, bachelor of science in nursing vs master of science in nursing as a terminal degree). Physician assistant students are required to complete 2000 prelicensure clinical hours, and most PA programs are 3 years in duration.⁴ Many NP and PA programs require some degree of clinical experience prior to beginning graduate education.⁵

When comparing prelicensure examinations, questions assessing dermatologic knowledge comprise approximately 6% to 10% of the total questions on the United States Medical Licensing Examination Steps 1 and 2.⁶ The Comprehensive Osteopathic Medical Licensing Examination of the United States Level 1 and Level 2-Cognitive Evaluation both have at least 5% of questions dedicated to dermatology.⁷ Approximately 5% of the questions on the Physician Assistant National Certifying Examination are dedicated to dermatology.⁸ The dermatology content on either of the NP certification examinations is unclear.^2,3 In the states of California, Indiana, and New York, national certification through the American Association of Nurse Practitioners or American Nurses Credentialing Center is not required for NPs to practice in their respective states.⁹

Regarding dermatologic board certification, a new graduate NP may obtain certification from the Dermatology Nurse Practitioner Certification Board with 3000 hours of general dermatology practice that may occur during normal working hours.¹⁰ These hours do not have to occur in one of the previously identified postgraduate APP training programs. The National Board of Dermatology Physician Assistants was founded in 2018 and has since dissolved. The National Board of Dermatology Physician Assistants was not accredited and required at least 3 years of training in dermatology with the same dermatologist in addition to completing a 125-question multiple-choice examination.¹¹ Of note, this examination was opposed by both the ABD and the Society for Dermatology Physician Associates.¹² A PA also may become a Diplomate Fellow with the Society of Dermatology Physician Associates after completion of 64.5 hours of online continuing education modules.⁴ Some PAs may choose to obtain a Certificate of Added Qualifications, which is a voluntary credential that helps document specialty experience and expertise in dermatology or other specialties.

In contrast, a dermatology resident physician requires nearly 11,000 to 13,000 hours of clinical training hours, which last 3 to 4 years following medical school.¹³ This training involves direct patient care under supervision in various settings, including hospitals, outpatient clinics, and surgical procedures. In addition to this clinical experience, dermatology residents must pass a 3-step certification examination process administered by the ABD.¹³ This process includes approximately 20 hours of examinations designed to assess both knowledge and practical skills. For those who wish to further specialize, additional fellowship training in areas such as pediatric dermatology, dermatopathology, or Mohs surgery may follow residency; such fellowships involve an extra 2500 to 3500 hours of training and culminate in another certification examination, further refining a resident’s expertise in a specific dermatologic field. Osteopathic physicians may opt out of the ABD 3-step pathway and obtain board certification through the American Osteopathic Board of Dermatology.¹⁴

Many of the programs we evaluated integrate APP trainees into resident education, allowing participation in equivalent didactic curricula, clinical rotations, and departmental academic activities. The salary and benefits associated with these programs are somewhat like those of resident physicians.^15,16 While most tuition-based programs were excluded from our study due to their lack of credibility and alignment with our study criteria, we identified 2 specific programs that stood out as credible despite requiring students to pay tuition. These programs demonstrated a structured and rigorous curriculum with a clear focus on comprehensive dermatologic training, meeting our standards for inclusion. These programs offer dermatologic training for graduates of NP and PA programs at a cost to the student.^15,16 The program at the Florida Atlantic University, Boca Raton, is largely online,¹⁵ and the program at the University of Miami, Florida, offers no direct clinical contact.¹⁶ These programs illustrate the variety of postgraduate dermatology curricula available nationally in comparison to resident salaries; however, they were not included in our formal analysis because they do not provide structured, in-person clinical training consistent with our inclusion criteria. Neither of these programs would enable participants to qualify for credentialing with the Dermatology Nurse Practitioner Certification Board after completion. While this study identified postgraduate training programs for APPs in dermatology advertised online, it is possible some were omitted or not advertised online.

While many of the postgraduate programs we evaluated provide unique educational opportunities for APPs, it is unknown if graduating providers are equipped to handle the care of patients with complex dermatologic needs. Regardless, the increased utilization of APPs by BCDs has been well documented over the past 2 decades.^17-20 It has been suggested that a higher ratio of APPs to dermatologists can decrease the time it takes for a patient to be seen in a clinic.^21-23 However, investigators have expressed concerns that APPs lack standardized surgical training and clinical hour requirements in the field of dermatology.²⁴ Despite these concerns, Medicare claims data show that APPs are performing advanced surgical and cosmetic procedures at increasing rates.^17,18 Other authors have questioned the cost-effectiveness of APPs, as multiple studies have shown that the number of biopsies needed to diagnose 1 case of skin cancer is higher for midlevel providers than for dermatologists.^25-27

Conclusion

With the anticipated expansion of private equity in dermatology and the growth of our Medicare-eligible population, we are likely to see increased utilization of APPs to address the shortage of BCDs.^28,29 Understanding the prelicensure and postlicensure clinical training requirements, examination hours, and extent of dermatology-focused education among APPs and BCDs can help dermatologists collaborate more effectively and ensure safe, high-quality patient care. Standardizing, improving, and providing high-quality education and promoting lifelong learning in the field of dermatology should be celebrated, and dermatologists are the skin experts best equipped to lead dermatologic education forward.

Practice Gap

Tattoos have become increasingly prevalent in Western culture, with approximately 1 in 4 Americans having at least 1 tattoo. Individuals invest money, time, and even pain in getting tattoos, many of which hold special personal, family, or religious significance.¹ Various cutaneous pathologies may arise in areas of the skin with tattoos, including malignancies and inflammatory reactions to tattoo pigment, and in these cases, surgical management may be indicated.^2,3

Nonmelanoma skin cancers (NMSCs) such as superficial basal cell carcinomas on broadly sun-damaged areas (eg, trunk, torso), squamous cell carcinomas, reactive keratoacanthomas, and reactive pseudoepitheliomatous squamous hyperplasia diagnosed as squamous cell carcinoma have been reported to occur in or near areas of the skin with tattoos.² Mohs micrographic surgery (MMS) is the standard of care for removing NMSCs, particularly when they manifest in cosmetically sensitive areas.⁴ This treatment option allows for careful guided resection of tumors to minimize the risk for recurrence; it also preserves healthy tissue, which typically results in a smaller radial defect after the procedure is complete. 

Chronic reactions to tattoo pigment may include granulomatous tattoo reactions and pseudolymphomas.³ Treatment options may include immunosuppressives such as intralesional triamcinolone as well as pigment destruction via lasers⁵; however, not all tattoos are responsive to these treatments. Surgical excision is an effective and definitive treatment in this context, as tattoo pigment resides in or above the mid dermis to a depth of approximately 400 μm. Intradermal excision effectively removes the antigenic pigment.⁵

In these clinical scenarios, patients may be hesitant to pursue surgical treatment due to concerns that it may alter tattoo appearance. Many clinicians and surgeons may consider definitive treatment and tattoo preservation to be mutually exclusive, but this is not always the case. We propose a technique that utilizes conservative thickness layers (CTL) to minimize disruption to the appearance of tattoos in MMS for treatment of cutaneous malignancies as well as intradermal excision of tattoo pigment in the setting of chronic inflammatory tattoo reactions.

The Technique

In the appropriate clinical context, CTL can effectively result in defects that heal well by secondary intention and minimize collateral tissue distortion.⁴ Lesions manifesting in or near tattooed skin often are responsive to treatment with CTL; furthermore, CTL may preserve some deeper tattoo pigment, resulting in only partial loss of the tattooed skin.

Conservative thickness layers are performed intradermally, similar to removing traditional layers in MMS. For treatment of NMSCs, a margin is scored around the lesion, and then the blade is passed carefully under the lesion nearly parallel to the skin through an intradermal plane. It is important to avoid entering the subcuticular fat (Figure 1). The tissue then is processed normally in the Mohs laboratory for complete circumferential margin evaluation. If necessary and possible, subsequent layers also can be performed in the intradermal plane. Once total circumferential margin control is obtained, the wound is allowed to granulate and heal by secondary intention. As these processes occur, we have found that wound contraction is less likely with the dermis intact, resulting in less impact on the overall appearance of the tattoo (Figures 1 and 2). For very thin lesions, resultant defects may retain some residual tattoo pigment. The residual scars also may be responsive to tattoo revision, although a period of monitoring for recurrence should be considered if there is concern that revising the tattoo could obscure early recurrent tumors. From our experience, utilizing CTL for NMSCs that arise within or near tattoos results in favorable preservation of the tattoo appearance and high patient satisfaction.

The procedure is performed similarly for removal of allergenic tattoo pigment, with careful excision to the mid dermis. Since the areas affected by the cutaneous reaction may be relatively large, surgical precision is required to maintain a uniform depth to remove the tattoo pigment and preserve the deep dermis (Figure 2). Once removed, the defect can be left to granulate and heal by secondary intention. If the patient wants to have the tattoo revised in the future, it would be prudent to utilize pigment that the patient has responded favorably to. In our experience, this approach is effective and yields high patient satisfaction and minimizes morbidity.

Practice Implications

Tattoos often hold special meaning for patients; therefore, treatment of pathologies arising in or near tattooed skin should emphasize maintaining the appearance of the tattoo while still being effective. Conservative thickness layers in MMS and intradermal excisions for allergic reactions to tattoo pigment are an effective treatment strategy that clinicians may consider.

One shortcoming of using CTL for MMS is the need for subsequent layers to clear the tumor; however, data suggest that first-stage cure rates are extremely high even with CTL for appropriately selected patients, with clearance of nearly 80% of tumors on the first stage. Tumors that may be most responsive to CTL include exophytic NMSCs and those arising in areas with a thicker dermis, including the back, legs, and scalp, although other locations including the face, hands, shins, ankles, and feet also may be well suited for CTL.⁴ Another shortcoming of CTL is that skin cancers arising in tattoos may not be considered appropriate for MMS based on the 2012 Appropriate Use Criteria, which consider factors such as location, type of cancer, size of the lesion, and patient characteristics to determine whether a skin cancer is appropriate for treatment with MMS.⁶ When the Appropriate Use Criteria categorizes a cancer as uncertain or inappropriate for MMS, the clinician must use their clinical judgment to determine whether MMS is the preferred treatment approach.⁷ Given the cosmetic significance of tattoos, location of a skin cancer near a tattoo could be taken into account for skin cancers that might otherwise not meet Appropriate Use Criteria. 

Conservative thickness layers in MMS and intradermal excisions of tattoo pigment are both effective techniques of minimizing disruption of tattoos while effectively treating patients.

Practice Gap

Tattoos have become increasingly prevalent in Western culture, with approximately 1 in 4 Americans having at least 1 tattoo. Individuals invest money, time, and even pain in getting tattoos, many of which hold special personal, family, or religious significance.¹ Various cutaneous pathologies may arise in areas of the skin with tattoos, including malignancies and inflammatory reactions to tattoo pigment, and in these cases, surgical management may be indicated.^2,3

Nonmelanoma skin cancers (NMSCs) such as superficial basal cell carcinomas on broadly sun-damaged areas (eg, trunk, torso), squamous cell carcinomas, reactive keratoacanthomas, and reactive pseudoepitheliomatous squamous hyperplasia diagnosed as squamous cell carcinoma have been reported to occur in or near areas of the skin with tattoos.² Mohs micrographic surgery (MMS) is the standard of care for removing NMSCs, particularly when they manifest in cosmetically sensitive areas.⁴ This treatment option allows for careful guided resection of tumors to minimize the risk for recurrence; it also preserves healthy tissue, which typically results in a smaller radial defect after the procedure is complete. 

Chronic reactions to tattoo pigment may include granulomatous tattoo reactions and pseudolymphomas.³ Treatment options may include immunosuppressives such as intralesional triamcinolone as well as pigment destruction via lasers⁵; however, not all tattoos are responsive to these treatments. Surgical excision is an effective and definitive treatment in this context, as tattoo pigment resides in or above the mid dermis to a depth of approximately 400 μm. Intradermal excision effectively removes the antigenic pigment.⁵

In these clinical scenarios, patients may be hesitant to pursue surgical treatment due to concerns that it may alter tattoo appearance. Many clinicians and surgeons may consider definitive treatment and tattoo preservation to be mutually exclusive, but this is not always the case. We propose a technique that utilizes conservative thickness layers (CTL) to minimize disruption to the appearance of tattoos in MMS for treatment of cutaneous malignancies as well as intradermal excision of tattoo pigment in the setting of chronic inflammatory tattoo reactions.

The Technique

In the appropriate clinical context, CTL can effectively result in defects that heal well by secondary intention and minimize collateral tissue distortion.⁴ Lesions manifesting in or near tattooed skin often are responsive to treatment with CTL; furthermore, CTL may preserve some deeper tattoo pigment, resulting in only partial loss of the tattooed skin.

Conservative thickness layers are performed intradermally, similar to removing traditional layers in MMS. For treatment of NMSCs, a margin is scored around the lesion, and then the blade is passed carefully under the lesion nearly parallel to the skin through an intradermal plane. It is important to avoid entering the subcuticular fat (Figure 1). The tissue then is processed normally in the Mohs laboratory for complete circumferential margin evaluation. If necessary and possible, subsequent layers also can be performed in the intradermal plane. Once total circumferential margin control is obtained, the wound is allowed to granulate and heal by secondary intention. As these processes occur, we have found that wound contraction is less likely with the dermis intact, resulting in less impact on the overall appearance of the tattoo (Figures 1 and 2). For very thin lesions, resultant defects may retain some residual tattoo pigment. The residual scars also may be responsive to tattoo revision, although a period of monitoring for recurrence should be considered if there is concern that revising the tattoo could obscure early recurrent tumors. From our experience, utilizing CTL for NMSCs that arise within or near tattoos results in favorable preservation of the tattoo appearance and high patient satisfaction.

The procedure is performed similarly for removal of allergenic tattoo pigment, with careful excision to the mid dermis. Since the areas affected by the cutaneous reaction may be relatively large, surgical precision is required to maintain a uniform depth to remove the tattoo pigment and preserve the deep dermis (Figure 2). Once removed, the defect can be left to granulate and heal by secondary intention. If the patient wants to have the tattoo revised in the future, it would be prudent to utilize pigment that the patient has responded favorably to. In our experience, this approach is effective and yields high patient satisfaction and minimizes morbidity.

Practice Implications

Tattoos often hold special meaning for patients; therefore, treatment of pathologies arising in or near tattooed skin should emphasize maintaining the appearance of the tattoo while still being effective. Conservative thickness layers in MMS and intradermal excisions for allergic reactions to tattoo pigment are an effective treatment strategy that clinicians may consider.

One shortcoming of using CTL for MMS is the need for subsequent layers to clear the tumor; however, data suggest that first-stage cure rates are extremely high even with CTL for appropriately selected patients, with clearance of nearly 80% of tumors on the first stage. Tumors that may be most responsive to CTL include exophytic NMSCs and those arising in areas with a thicker dermis, including the back, legs, and scalp, although other locations including the face, hands, shins, ankles, and feet also may be well suited for CTL.⁴ Another shortcoming of CTL is that skin cancers arising in tattoos may not be considered appropriate for MMS based on the 2012 Appropriate Use Criteria, which consider factors such as location, type of cancer, size of the lesion, and patient characteristics to determine whether a skin cancer is appropriate for treatment with MMS.⁶ When the Appropriate Use Criteria categorizes a cancer as uncertain or inappropriate for MMS, the clinician must use their clinical judgment to determine whether MMS is the preferred treatment approach.⁷ Given the cosmetic significance of tattoos, location of a skin cancer near a tattoo could be taken into account for skin cancers that might otherwise not meet Appropriate Use Criteria. 

Conservative thickness layers in MMS and intradermal excisions of tattoo pigment are both effective techniques of minimizing disruption of tattoos while effectively treating patients.

Practice Gap

Tattoos have become increasingly prevalent in Western culture, with approximately 1 in 4 Americans having at least 1 tattoo. Individuals invest money, time, and even pain in getting tattoos, many of which hold special personal, family, or religious significance.¹ Various cutaneous pathologies may arise in areas of the skin with tattoos, including malignancies and inflammatory reactions to tattoo pigment, and in these cases, surgical management may be indicated.^2,3

Nonmelanoma skin cancers (NMSCs) such as superficial basal cell carcinomas on broadly sun-damaged areas (eg, trunk, torso), squamous cell carcinomas, reactive keratoacanthomas, and reactive pseudoepitheliomatous squamous hyperplasia diagnosed as squamous cell carcinoma have been reported to occur in or near areas of the skin with tattoos.² Mohs micrographic surgery (MMS) is the standard of care for removing NMSCs, particularly when they manifest in cosmetically sensitive areas.⁴ This treatment option allows for careful guided resection of tumors to minimize the risk for recurrence; it also preserves healthy tissue, which typically results in a smaller radial defect after the procedure is complete. 

Chronic reactions to tattoo pigment may include granulomatous tattoo reactions and pseudolymphomas.³ Treatment options may include immunosuppressives such as intralesional triamcinolone as well as pigment destruction via lasers⁵; however, not all tattoos are responsive to these treatments. Surgical excision is an effective and definitive treatment in this context, as tattoo pigment resides in or above the mid dermis to a depth of approximately 400 μm. Intradermal excision effectively removes the antigenic pigment.⁵

In these clinical scenarios, patients may be hesitant to pursue surgical treatment due to concerns that it may alter tattoo appearance. Many clinicians and surgeons may consider definitive treatment and tattoo preservation to be mutually exclusive, but this is not always the case. We propose a technique that utilizes conservative thickness layers (CTL) to minimize disruption to the appearance of tattoos in MMS for treatment of cutaneous malignancies as well as intradermal excision of tattoo pigment in the setting of chronic inflammatory tattoo reactions.

The Technique

In the appropriate clinical context, CTL can effectively result in defects that heal well by secondary intention and minimize collateral tissue distortion.⁴ Lesions manifesting in or near tattooed skin often are responsive to treatment with CTL; furthermore, CTL may preserve some deeper tattoo pigment, resulting in only partial loss of the tattooed skin.

Conservative thickness layers are performed intradermally, similar to removing traditional layers in MMS. For treatment of NMSCs, a margin is scored around the lesion, and then the blade is passed carefully under the lesion nearly parallel to the skin through an intradermal plane. It is important to avoid entering the subcuticular fat (Figure 1). The tissue then is processed normally in the Mohs laboratory for complete circumferential margin evaluation. If necessary and possible, subsequent layers also can be performed in the intradermal plane. Once total circumferential margin control is obtained, the wound is allowed to granulate and heal by secondary intention. As these processes occur, we have found that wound contraction is less likely with the dermis intact, resulting in less impact on the overall appearance of the tattoo (Figures 1 and 2). For very thin lesions, resultant defects may retain some residual tattoo pigment. The residual scars also may be responsive to tattoo revision, although a period of monitoring for recurrence should be considered if there is concern that revising the tattoo could obscure early recurrent tumors. From our experience, utilizing CTL for NMSCs that arise within or near tattoos results in favorable preservation of the tattoo appearance and high patient satisfaction.

The procedure is performed similarly for removal of allergenic tattoo pigment, with careful excision to the mid dermis. Since the areas affected by the cutaneous reaction may be relatively large, surgical precision is required to maintain a uniform depth to remove the tattoo pigment and preserve the deep dermis (Figure 2). Once removed, the defect can be left to granulate and heal by secondary intention. If the patient wants to have the tattoo revised in the future, it would be prudent to utilize pigment that the patient has responded favorably to. In our experience, this approach is effective and yields high patient satisfaction and minimizes morbidity.

Practice Implications

Tattoos often hold special meaning for patients; therefore, treatment of pathologies arising in or near tattooed skin should emphasize maintaining the appearance of the tattoo while still being effective. Conservative thickness layers in MMS and intradermal excisions for allergic reactions to tattoo pigment are an effective treatment strategy that clinicians may consider.

One shortcoming of using CTL for MMS is the need for subsequent layers to clear the tumor; however, data suggest that first-stage cure rates are extremely high even with CTL for appropriately selected patients, with clearance of nearly 80% of tumors on the first stage. Tumors that may be most responsive to CTL include exophytic NMSCs and those arising in areas with a thicker dermis, including the back, legs, and scalp, although other locations including the face, hands, shins, ankles, and feet also may be well suited for CTL.⁴ Another shortcoming of CTL is that skin cancers arising in tattoos may not be considered appropriate for MMS based on the 2012 Appropriate Use Criteria, which consider factors such as location, type of cancer, size of the lesion, and patient characteristics to determine whether a skin cancer is appropriate for treatment with MMS.⁶ When the Appropriate Use Criteria categorizes a cancer as uncertain or inappropriate for MMS, the clinician must use their clinical judgment to determine whether MMS is the preferred treatment approach.⁷ Given the cosmetic significance of tattoos, location of a skin cancer near a tattoo could be taken into account for skin cancers that might otherwise not meet Appropriate Use Criteria. 

Conservative thickness layers in MMS and intradermal excisions of tattoo pigment are both effective techniques of minimizing disruption of tattoos while effectively treating patients.

The biopsy revealed hyperkeratosis, hypergranulosis, follicular plugging, vacuolar interface dermatitis with apoptotic bodies, dyskeratotic keratinocytes, pigment incontinence, and melanophages. A perivascular, perifollicular, and periadnexal lymphoplasmacytic inflammatory infiltrate was noted in the superficial and deep dermis (Figure). Based on the characteristic clinical morphology, dermoscopic features, and histopathology, a diagnosis of discoid lupus erythematosus (DLE) was established. The patient was started on mometasone cream 0.1% and tacrolimus ointment 0.1% once daily, with strict recommendations for photoprotection. However, he subsequently was lost to follow-up, and treatment response could not be assessed.

Lupus erythematosus is a multisystemic autoimmune disease with a predilection for skin involvement that is characterized by the production of autoantibodies against nuclear antigens. Discoid lupus erythematosus is the predominant form of the disease, mostly affecting middle-aged women (female-to-male ratio, 4.1:1).¹ Discoid lupus erythematosus usually manifests as well-demarcated, erythematous patches or plaques with partially adherent scales that extend into a patulous follicle. On removal, the scales show horny plugs underneath. This classic finding is known as the carpet tack sign.

As the lesions evolve, they expand with hyperpigmentation at the periphery as well as hypopigmentation, atrophy, scarring, and telangiectasias at the center.² In our patient, the history of discharge and crusting of the lesion and the presence of slight central atrophy—all of which could be attributed to chronic application of topical medications such as corticosteroids, which can cause epidermal thinning, maceration, and secondary crust formation—raised clinical suspicion of cutaneous infections (eg, cutaneous leishmaniasis, lupus vulgaris) and squamous cell carcinoma. The presence of slightly raised margins upon clinical examination brought basal cell carcinoma (BCC) into the differential.

Dermoscopic features commonly seen in DLE reflect the pathologic findings. Follicular plugging and perifollicular white halos correspond to follicular hyperkeratosis and perifollicular fibrosis, respectively (eTable). Disease duration has been shown to alter the dermoscopic appearance of DLE with early active disease showing radially arranged arborizing blood vessels between perifollicular white halos along with follicular red dots, whereas lesions of longer duration display structureless white areas secondary to dermal fibrosis.³ Additionally, background erythema due to neoangiogenesis and dermal inflammation suggests that the disease is in its active state.

On dermoscopy, pigmentation structures such as brown dots, brown lines, and grey-brown dots and globules were seen more prominently in our patient with skin of color, making the underlying erythema more subtle than in patients with lighter skin types. Dotted and linear vessels also were seen in our patient, but not as prominently as typically is seen in lighter skin types.⁴

Lupus vulgaris was ruled out in our patient based on the absence of the typical orange to yellowish-orange background with vessels or any histopathologic evidence of epithelioid granulomas.⁵ Cutaneous leishmaniasis is characterized by polymorphic vascularization, erythema, follicular plugs, yellow-orange structureless areas with scales, and crusts on dermoscopy.⁶ Squamous cell carcinoma tends to show white structureless areas, looped vessels, and central keratin.⁷

Superficial BCC also appears as thin plaques or patches bound by a well-circumscribed, slightly raised, irregular margin. However, on dermoscopy, BCC typically exhibits spoke-wheel areas, arborizing vessels, comma vessels, and concentric structures.⁸

The clinical manifestations of crusting, discharge, and a raised border was atypical, probably owing to the long-term unsupervised application of topical medications, which made the initial diagnosis challenging. Therefore, various differential diagnoses were considered. Dermoscopic evaluation coupled with histology was performed, which ultimately confirmed the diagnosis of DLE.

The biopsy revealed hyperkeratosis, hypergranulosis, follicular plugging, vacuolar interface dermatitis with apoptotic bodies, dyskeratotic keratinocytes, pigment incontinence, and melanophages. A perivascular, perifollicular, and periadnexal lymphoplasmacytic inflammatory infiltrate was noted in the superficial and deep dermis (Figure). Based on the characteristic clinical morphology, dermoscopic features, and histopathology, a diagnosis of discoid lupus erythematosus (DLE) was established. The patient was started on mometasone cream 0.1% and tacrolimus ointment 0.1% once daily, with strict recommendations for photoprotection. However, he subsequently was lost to follow-up, and treatment response could not be assessed.

Lupus erythematosus is a multisystemic autoimmune disease with a predilection for skin involvement that is characterized by the production of autoantibodies against nuclear antigens. Discoid lupus erythematosus is the predominant form of the disease, mostly affecting middle-aged women (female-to-male ratio, 4.1:1).¹ Discoid lupus erythematosus usually manifests as well-demarcated, erythematous patches or plaques with partially adherent scales that extend into a patulous follicle. On removal, the scales show horny plugs underneath. This classic finding is known as the carpet tack sign.

As the lesions evolve, they expand with hyperpigmentation at the periphery as well as hypopigmentation, atrophy, scarring, and telangiectasias at the center.² In our patient, the history of discharge and crusting of the lesion and the presence of slight central atrophy—all of which could be attributed to chronic application of topical medications such as corticosteroids, which can cause epidermal thinning, maceration, and secondary crust formation—raised clinical suspicion of cutaneous infections (eg, cutaneous leishmaniasis, lupus vulgaris) and squamous cell carcinoma. The presence of slightly raised margins upon clinical examination brought basal cell carcinoma (BCC) into the differential.

Dermoscopic features commonly seen in DLE reflect the pathologic findings. Follicular plugging and perifollicular white halos correspond to follicular hyperkeratosis and perifollicular fibrosis, respectively (eTable). Disease duration has been shown to alter the dermoscopic appearance of DLE with early active disease showing radially arranged arborizing blood vessels between perifollicular white halos along with follicular red dots, whereas lesions of longer duration display structureless white areas secondary to dermal fibrosis.³ Additionally, background erythema due to neoangiogenesis and dermal inflammation suggests that the disease is in its active state.

On dermoscopy, pigmentation structures such as brown dots, brown lines, and grey-brown dots and globules were seen more prominently in our patient with skin of color, making the underlying erythema more subtle than in patients with lighter skin types. Dotted and linear vessels also were seen in our patient, but not as prominently as typically is seen in lighter skin types.⁴

Lupus vulgaris was ruled out in our patient based on the absence of the typical orange to yellowish-orange background with vessels or any histopathologic evidence of epithelioid granulomas.⁵ Cutaneous leishmaniasis is characterized by polymorphic vascularization, erythema, follicular plugs, yellow-orange structureless areas with scales, and crusts on dermoscopy.⁶ Squamous cell carcinoma tends to show white structureless areas, looped vessels, and central keratin.⁷

Superficial BCC also appears as thin plaques or patches bound by a well-circumscribed, slightly raised, irregular margin. However, on dermoscopy, BCC typically exhibits spoke-wheel areas, arborizing vessels, comma vessels, and concentric structures.⁸

The clinical manifestations of crusting, discharge, and a raised border was atypical, probably owing to the long-term unsupervised application of topical medications, which made the initial diagnosis challenging. Therefore, various differential diagnoses were considered. Dermoscopic evaluation coupled with histology was performed, which ultimately confirmed the diagnosis of DLE.

The biopsy revealed hyperkeratosis, hypergranulosis, follicular plugging, vacuolar interface dermatitis with apoptotic bodies, dyskeratotic keratinocytes, pigment incontinence, and melanophages. A perivascular, perifollicular, and periadnexal lymphoplasmacytic inflammatory infiltrate was noted in the superficial and deep dermis (Figure). Based on the characteristic clinical morphology, dermoscopic features, and histopathology, a diagnosis of discoid lupus erythematosus (DLE) was established. The patient was started on mometasone cream 0.1% and tacrolimus ointment 0.1% once daily, with strict recommendations for photoprotection. However, he subsequently was lost to follow-up, and treatment response could not be assessed.

Lupus erythematosus is a multisystemic autoimmune disease with a predilection for skin involvement that is characterized by the production of autoantibodies against nuclear antigens. Discoid lupus erythematosus is the predominant form of the disease, mostly affecting middle-aged women (female-to-male ratio, 4.1:1).¹ Discoid lupus erythematosus usually manifests as well-demarcated, erythematous patches or plaques with partially adherent scales that extend into a patulous follicle. On removal, the scales show horny plugs underneath. This classic finding is known as the carpet tack sign.

As the lesions evolve, they expand with hyperpigmentation at the periphery as well as hypopigmentation, atrophy, scarring, and telangiectasias at the center.² In our patient, the history of discharge and crusting of the lesion and the presence of slight central atrophy—all of which could be attributed to chronic application of topical medications such as corticosteroids, which can cause epidermal thinning, maceration, and secondary crust formation—raised clinical suspicion of cutaneous infections (eg, cutaneous leishmaniasis, lupus vulgaris) and squamous cell carcinoma. The presence of slightly raised margins upon clinical examination brought basal cell carcinoma (BCC) into the differential.

Dermoscopic features commonly seen in DLE reflect the pathologic findings. Follicular plugging and perifollicular white halos correspond to follicular hyperkeratosis and perifollicular fibrosis, respectively (eTable). Disease duration has been shown to alter the dermoscopic appearance of DLE with early active disease showing radially arranged arborizing blood vessels between perifollicular white halos along with follicular red dots, whereas lesions of longer duration display structureless white areas secondary to dermal fibrosis.³ Additionally, background erythema due to neoangiogenesis and dermal inflammation suggests that the disease is in its active state.

On dermoscopy, pigmentation structures such as brown dots, brown lines, and grey-brown dots and globules were seen more prominently in our patient with skin of color, making the underlying erythema more subtle than in patients with lighter skin types. Dotted and linear vessels also were seen in our patient, but not as prominently as typically is seen in lighter skin types.⁴

Lupus vulgaris was ruled out in our patient based on the absence of the typical orange to yellowish-orange background with vessels or any histopathologic evidence of epithelioid granulomas.⁵ Cutaneous leishmaniasis is characterized by polymorphic vascularization, erythema, follicular plugs, yellow-orange structureless areas with scales, and crusts on dermoscopy.⁶ Squamous cell carcinoma tends to show white structureless areas, looped vessels, and central keratin.⁷

Superficial BCC also appears as thin plaques or patches bound by a well-circumscribed, slightly raised, irregular margin. However, on dermoscopy, BCC typically exhibits spoke-wheel areas, arborizing vessels, comma vessels, and concentric structures.⁸

The clinical manifestations of crusting, discharge, and a raised border was atypical, probably owing to the long-term unsupervised application of topical medications, which made the initial diagnosis challenging. Therefore, various differential diagnoses were considered. Dermoscopic evaluation coupled with histology was performed, which ultimately confirmed the diagnosis of DLE.

Sporotrichosis is an implantation mycosis that classically manifests as a localized skin and subcutaneous fungal infection but may disseminate to other parts of the body.¹ It is caused by several species within the Sporothrix genus² and is associated with varying clinical manifestations, geographic distributions, virulence profiles, and antifungal susceptibility patterns.^3,4 Transmission of the fungus can involve inoculation from wild or domestic animals (eg, cats).^5,6 Occupations such as landscaping and gardening or elements in the environment (eg, soil, plant fragments) also can be sources of exposure.^7,8

Sporotrichosis is recognized by the World Health Organization as a neglected tropical disease that warrants global advocacy to prevent infections and improve patient outcomes.^9,10 It carries substantial stigma and socioeconomic burden.^11,12 Diagnostics, species identification, and antifungal susceptibility testing often are limited, particularly in resource-limited settings.¹³ In this article, we outline steps to diagnose and manage sporotrichosis to improve care for affected patients globally.

Epidemiology

Sporotrichosis occurs worldwide but is most common in tropical and subtropical regions.^14,15 Outbreaks and clusters of sporotrichosis have been observed across North, Central, and South America as well as in southern Africa and Asia. The estimated annual incidence is 40,000 cases worldwide,^16-20 but global case counts likely are underestimated due to limited surveillance data and diagnostic capability.²¹

On the Asian subcontinent, Sporothrix globosa is the predominant causative species of sporotrichosis, typically via contaminated plant material²²; however, at least 1 outbreak has been associated with severe flooding.²³ In Africa, infections are most commonly caused by Sporothrix schenckii sensu stricto through a similar transmission route. Across Central America, S schenckii sensu stricto is the predominant causative species; however, Sporothrix brasiliensis is the predominant species in some countries in South America, particularly Brazil.²⁰   

Data describing the current geographic distribution and prevalence of sporotrichosis in the United States are limited. Historically, the disease was reported most commonly in Midwestern states and was associated with outbreaks related to handling Sphagnum moss.^24,25 Epidemiologic studies using health insurance data indicate an average annual incidence of 2.0 cases per million individuals in the United States, with a higher prevalence among women and a median age at diagnosis of 54 years.²⁶ A review of sporotrichosis-associated hospitalizations across the United States from 2000 to 2013 indicated an average hospitalization rate of 0.35 cases per 1 million individuals; rates were higher (0.45 cases per million) in the West and lower (0.15 per million) in the Northeast and in men (0.40 per million).²⁷ Type 2 diabetes, immune-mediated inflammatory disease, and chronic obstructive pulmonary disease are associated with an increased risk for infection and hospitalization.²⁷

Causative Organisms

Sporothrix species are thermally dimorphic fungi that can grow as mold in the environment and as yeast in human tissue. Sporothrix brasiliensis is the only thermodimorphic fungus known to be transmitted directly in its yeast form.²⁸ In other species, inoculation usually occurs after contact with contaminated soil or plant material during gardening, carpentry, or agricultural practices.⁷

Zoonotic transmission of sporotrichosis from animals to humans has been reported from a range of domestic and wild animals and birds but historically has been rare.^5,7,29,30 Recently, the importance of both cat-to-cat (epizootic) and cat-to-human (zoonotic) transmission of S brasiliensis has been recognized, with infection typically following traumatic inoculation after a scratch or bite; less frequently, transmission occurs due to exposure to respiratory droplets or contact with feline exudates.^5,29,31Sporothrix brasiliensis is responsible for zoonotic epidemics in South America, primarily in Brazil. Transmission occurs among humans, cats, and canines, with felines serving as the primary vector.³² Transmission of this species is particularly common in stray and unneutered male cats that exhibit aggressive behaviors.³³ This species also is thought to be the most virulent Sporothrix species.²¹

Sporothrix brasiliensis can persist on nondisinfected inanimate surfaces, which suggests that fomite transmission can lead to human infection.³¹ The epidemiology of sporotrichosis has transformed in regions where S brasiliensis circulates, with epidemic spread resulting in thousands of cases, whereas in other areas without S brasilinesis, sporotrichosis predominantly occurs sporadically with rare clusters.^1,2,7,15

Sporotrichosis has been the subject of a taxonomic debate in the mycology community.²¹Sporothrix schenckii sensu lato originally was believed to be the sole fungal pathogen causing sporotrichosis³⁴ but was later divided into S schenckii sensu stricto, Sporothrix globosa, and S brasiliensis.³⁵ More than 60 distinct species now have been described within the Sporothrix genus,^36,37 but the primary species causing human sporotrichosis include S schenckii sensu stricto, S brasiliensis, S globosa, Sporothrix mexicana, and Sporothrix luriei.³⁵ Both S schenckii and S brasiliensis have greater virulence than other Sporothrix species⁴; however, S schenckii causes infections that typically are localized and are milder, while S brasiliensis can lead to more atypical, severe, and disseminated infections^38,39 and can spread epidemically.

Clinical Manifestations

Sporotrichosis has 4 main clinical presentations: cutaneous lymphatic, fixed cutaneous, cutaneous or systemic disseminated, and extracutaneous.^40,41 The most common clinical manifestation is the cutaneous lymphatic form, which predominantly affects the hands and forearms in adults and the face in children.⁷ The primary lesion usually manifests as a unilateral papule, nodule, or pustule that may ulcerate (sporotrichotic chancre), but multiple sites of inoculation are possible. Subsequent lesions may appear in a linear distribution along a regional lymphatic path (sporotrichoid spread). Systemic symptoms and regional lymphadenopathy are uncommon and usually are mild.

The second most common clinical manifestation is the fixed cutaneous form, typically affecting the face, neck, trunk, or legs with a single papule, nodule, or verrucous lesion with no lymphangitic spread.⁷ Usually confined to the inoculation site, the primary lesion may be accompanied by satellite lesions and often presents a diagnostic challenge.

Disseminated sporotrichosis (either cutaneous or systemic) is rare. Disseminated cutaneous sporotrichosis manifests with multiple noncontiguous skin lesions caused by lymphatic and possible hematogenous spread. Lesions may include a combination of papules, pustules, follicular eruptions, crusted plaques, and ulcers that may mimic other systemic infections. Immunoreactive changes such as erythema nodosum, erythema multiforme, or arthritis may accompany skin lesions, most commonly with S brasiliensis infections. Nearly 10% of S brasiliensis infections involve the ocular adnexa, and Parinaud oculoglandular syndrome is commonly described in cases reported in Brazil.^42,43 Disseminated disease usually occurs in immunocompromised hosts; however, despite a focus on HIV co-infection,^8,44 prior epidemiologic research has suggested that diabetes and alcoholism are the most common predisposing factors.⁴⁵ Systemic disseminated sporotrichosis by definition affects at least 2 body systems, most commonly the central nervous system, lungs, and musculoskeletal system (including joints and bone marrow).⁴⁵

Extracutaneous sporotrichosis is rare and often is difficult to diagnose. Risk factors include chronic obstructive pulmonary disease, alcoholism, use of steroid medications, AIDS, solid organ transplantation, and use of tumor necrosis factor α inhibitors. It usually affects bony structures through hematogenous spread in immunocompromised hosts and is associated with a high risk for osteomyelitis due to delayed diagnosis.²

Clinical progression of sporotrichosis usually is slow, and lesions may persist for months or years if untreated. Sporotrichosis should always be considered for atypical, persistent, or treatment-resistant manifestations of nodular or ulcerated skin lesions in endemic regions or acute illness with these symptoms following exposure. Preventing secondary bacterial infection is an important consideration as it can exacerbate disease severity, extend the treatment duration, prolong hospitalization, and increase mortality risk.⁴⁶

Diagnosis

In regions endemic for S brasiliensis, it may be acceptable to commence treatment on clinical suspicion without a definitive diagnosis,²¹ but caution is necessary, as lesions easily can be mistaken for other conditions such as Mycobacterium marinum infections (sporotrichoid lesions) or cutaneous leishmaniasis. Limited availability of molecular diagnostic tools in routine clinical laboratories affects the diagnosis of sporotrichosis and species identification. Direct microscopy on a 10% to 30% potassium hydroxide wet mount has low diagnostic sensitivity and is not recommended⁴⁷; findings typically include cigar-shaped yeast cells (eFigure 1). Biopsy and histopathology also are useful, although in many infections (other than those due to S brasiliensis) there are very few detectable organisms in the tissue. Fluorescent staining of fungi with optical brighteners (eg, Calcofluor, Blankophor) is a useful technique with high sensitivity in clinical specimens on histopathologic and direct examination.⁴⁸

Fungal culture has higher sensitivity and specificity than microscopy and is the gold-standard approach for diagnosis of sporotrichosis (eFigure 2); however, culture cannot differentiate between Sporothrix species and may take more than a month to yield a positive result.⁷ No reliable serologic test for sporotrichosis has been validated, and a standardized antigen assay currently is unavailable.⁴⁹ Serology may be more useful for patients who present with systemic disease or have persistently negative culture results despite a high index of suspicion. 

A recent study evaluated the effectiveness of a lateral flow assay for detecting anti-Sporothrix antibodies, demonstrating the potential for its use as a rapid diagnostic test.⁵⁰ Investigating different molecular methods to increase the sensitivity and specificity of diagnosis and distinguish Sporothrix species has been a focus of recent research, with a preference for polymerase chain reaction (PCR)–based genotypic methods.^13,51 Recent advances in diagnostic testing include the development of multiplex PCR,⁵² culture-independent PCR techniques,⁵³ and matrix-assisted laser desorption/ionization–time of flight mass spectrometry,⁵⁴ each with varying clinical and practical applicability. Specialized testing can be beneficial for patients who have a poor therapeutic response to standard treatment, guide antifungal treatment choices, and identify epidemiologic disease and transmission patterns.²¹

Although rarely performed, antifungal susceptibility testing may be useful in guiding therapy to improve patient outcomes, particularly in the context of treatment failure, which has been documented with isolates exhibiting high minimal inhibitory concentrations (MICs) to first-line therapy and a poor clinical response.^55,56 Proposed mechanisms of resistance include increased cellular melanin ­production, which protects against oxidative stress and reduces antifungal activity.⁵⁶ Antifungal susceptibility profiles for therapeutics vary across Sporothrix species; for example, S brasiliensis generally shows lower MICs to itraconazole and terbinafine compared with S schenckii and S globosa, and S schenckii has shown a high MIC to itraconazole, as reflected in MIC distribution studies and epidemiologic cutoff values for antifungal agents.^55,57-59 However, specific breakpoints for different Sporothrix species have not been determined.⁶⁰ Robust clinical studies are needed to determine the correlation of in vitro MICs to clinical outcomes to assess the utility of antifungal susceptibility testing for Sporothrix species.

Management

Treatment of sporotrichosis is guided by clinical presentation, host immune status, and species identification. Management can be challenging in cases with an atypical or delayed diagnosis and limited access to molecular testing methods. Itraconazole is the first-line therapy for management of cutaneous sporotrichosis. It is regarded as safe, effective, well tolerated, and easily administered, with doses ranging from 100 mg in mild cases to 400 mg (with daily or twice-daily dosing).⁶¹ Treatment usually is for 3 to 6 months and should continue for 1 month after complete clinical resolution is achieved⁶²; however, some cases of S brasiliensis infection require longer treatment, and complex or disseminated cases may require therapy for up to 12 months.⁶¹ Itraconazole is contraindicated in pregnancy and has many drug interactions (through cytochrome P450 inhibition) that may preclude administration, particularly in elderly populations. Therapeutic drug monitoring is recommended for prolonged or high-dose therapy, with periodic liver function testing to reduce the risk for toxicity. Itraconazole should be administered with food, and concurrent use of antacids or proton pump inhibitors should be avoided.⁶¹

Oral terbinafine (250 mg daily) can be considered as an effective alternative to treat cutaneous disease.⁶³ Particularly in resource-limited settings, potassium iodide is an affordable and effective treatment for cutaneous sporotrichosis, administered as a saturated oral solution,⁶⁴ but due to adverse effects such as severe nausea, the daily dose should be increased slowly each day to ensure tolerance.

Amphotericin B is the treatment of choice for severe and treatment-resistant cases of sporotrichosis as well as for immunocompromised patients.^21,61 In patients with HIV, a longer treatment course is recommended with oversight from an infectious diseases specialist and usually is followed by a 12-month course of itraconazole after completion of initial therapy.⁶¹ Surgical excision infrequently is recommended but can be used in combination with another treatment modality and may be useful with a slow or incomplete response to medical therapy. Thermotherapy involves direct application of heat to cutaneous lesions and may be considered for small and localized lesions, particularly if antifungal agents are contraindicated or poorly tolerated.⁶¹ Public health measures include promoting case detection through practitioner education and patient awareness in endemic regions, as well as zoonotic control of infected animals to manage sporotrichosis.

Final Thoughts

Sporotrichosis is a fungal infection with growing public health significance. While the global disease burden is unknown, rising case numbers and geographic spread likely reflect a complex interaction between humans, the environment, and animals, exemplified by the spread of feline-associated infection due to S brasiliensis in South America.²⁸ Cases of S brasiliensis infection after importation of an affected cat have been detected outside South America, and clinicians should be alert for introduction to the United States. Strengthening genotypic and phenotypic diagnostic capabilities will allow species identification and guide treatment and management. Disease surveillance and operational research will inform public health approaches to control sporotrichosis worldwide.

Sporotrichosis is an implantation mycosis that classically manifests as a localized skin and subcutaneous fungal infection but may disseminate to other parts of the body.¹ It is caused by several species within the Sporothrix genus² and is associated with varying clinical manifestations, geographic distributions, virulence profiles, and antifungal susceptibility patterns.^3,4 Transmission of the fungus can involve inoculation from wild or domestic animals (eg, cats).^5,6 Occupations such as landscaping and gardening or elements in the environment (eg, soil, plant fragments) also can be sources of exposure.^7,8

Sporotrichosis is recognized by the World Health Organization as a neglected tropical disease that warrants global advocacy to prevent infections and improve patient outcomes.^9,10 It carries substantial stigma and socioeconomic burden.^11,12 Diagnostics, species identification, and antifungal susceptibility testing often are limited, particularly in resource-limited settings.¹³ In this article, we outline steps to diagnose and manage sporotrichosis to improve care for affected patients globally.

Epidemiology

Sporotrichosis occurs worldwide but is most common in tropical and subtropical regions.^14,15 Outbreaks and clusters of sporotrichosis have been observed across North, Central, and South America as well as in southern Africa and Asia. The estimated annual incidence is 40,000 cases worldwide,^16-20 but global case counts likely are underestimated due to limited surveillance data and diagnostic capability.²¹

On the Asian subcontinent, Sporothrix globosa is the predominant causative species of sporotrichosis, typically via contaminated plant material²²; however, at least 1 outbreak has been associated with severe flooding.²³ In Africa, infections are most commonly caused by Sporothrix schenckii sensu stricto through a similar transmission route. Across Central America, S schenckii sensu stricto is the predominant causative species; however, Sporothrix brasiliensis is the predominant species in some countries in South America, particularly Brazil.²⁰   

Data describing the current geographic distribution and prevalence of sporotrichosis in the United States are limited. Historically, the disease was reported most commonly in Midwestern states and was associated with outbreaks related to handling Sphagnum moss.^24,25 Epidemiologic studies using health insurance data indicate an average annual incidence of 2.0 cases per million individuals in the United States, with a higher prevalence among women and a median age at diagnosis of 54 years.²⁶ A review of sporotrichosis-associated hospitalizations across the United States from 2000 to 2013 indicated an average hospitalization rate of 0.35 cases per 1 million individuals; rates were higher (0.45 cases per million) in the West and lower (0.15 per million) in the Northeast and in men (0.40 per million).²⁷ Type 2 diabetes, immune-mediated inflammatory disease, and chronic obstructive pulmonary disease are associated with an increased risk for infection and hospitalization.²⁷

Causative Organisms

Sporothrix species are thermally dimorphic fungi that can grow as mold in the environment and as yeast in human tissue. Sporothrix brasiliensis is the only thermodimorphic fungus known to be transmitted directly in its yeast form.²⁸ In other species, inoculation usually occurs after contact with contaminated soil or plant material during gardening, carpentry, or agricultural practices.⁷

Zoonotic transmission of sporotrichosis from animals to humans has been reported from a range of domestic and wild animals and birds but historically has been rare.^5,7,29,30 Recently, the importance of both cat-to-cat (epizootic) and cat-to-human (zoonotic) transmission of S brasiliensis has been recognized, with infection typically following traumatic inoculation after a scratch or bite; less frequently, transmission occurs due to exposure to respiratory droplets or contact with feline exudates.^5,29,31Sporothrix brasiliensis is responsible for zoonotic epidemics in South America, primarily in Brazil. Transmission occurs among humans, cats, and canines, with felines serving as the primary vector.³² Transmission of this species is particularly common in stray and unneutered male cats that exhibit aggressive behaviors.³³ This species also is thought to be the most virulent Sporothrix species.²¹

Sporothrix brasiliensis can persist on nondisinfected inanimate surfaces, which suggests that fomite transmission can lead to human infection.³¹ The epidemiology of sporotrichosis has transformed in regions where S brasiliensis circulates, with epidemic spread resulting in thousands of cases, whereas in other areas without S brasilinesis, sporotrichosis predominantly occurs sporadically with rare clusters.^1,2,7,15

Sporotrichosis has been the subject of a taxonomic debate in the mycology community.²¹Sporothrix schenckii sensu lato originally was believed to be the sole fungal pathogen causing sporotrichosis³⁴ but was later divided into S schenckii sensu stricto, Sporothrix globosa, and S brasiliensis.³⁵ More than 60 distinct species now have been described within the Sporothrix genus,^36,37 but the primary species causing human sporotrichosis include S schenckii sensu stricto, S brasiliensis, S globosa, Sporothrix mexicana, and Sporothrix luriei.³⁵ Both S schenckii and S brasiliensis have greater virulence than other Sporothrix species⁴; however, S schenckii causes infections that typically are localized and are milder, while S brasiliensis can lead to more atypical, severe, and disseminated infections^38,39 and can spread epidemically.

Clinical Manifestations

Sporotrichosis has 4 main clinical presentations: cutaneous lymphatic, fixed cutaneous, cutaneous or systemic disseminated, and extracutaneous.^40,41 The most common clinical manifestation is the cutaneous lymphatic form, which predominantly affects the hands and forearms in adults and the face in children.⁷ The primary lesion usually manifests as a unilateral papule, nodule, or pustule that may ulcerate (sporotrichotic chancre), but multiple sites of inoculation are possible. Subsequent lesions may appear in a linear distribution along a regional lymphatic path (sporotrichoid spread). Systemic symptoms and regional lymphadenopathy are uncommon and usually are mild.

The second most common clinical manifestation is the fixed cutaneous form, typically affecting the face, neck, trunk, or legs with a single papule, nodule, or verrucous lesion with no lymphangitic spread.⁷ Usually confined to the inoculation site, the primary lesion may be accompanied by satellite lesions and often presents a diagnostic challenge.

Disseminated sporotrichosis (either cutaneous or systemic) is rare. Disseminated cutaneous sporotrichosis manifests with multiple noncontiguous skin lesions caused by lymphatic and possible hematogenous spread. Lesions may include a combination of papules, pustules, follicular eruptions, crusted plaques, and ulcers that may mimic other systemic infections. Immunoreactive changes such as erythema nodosum, erythema multiforme, or arthritis may accompany skin lesions, most commonly with S brasiliensis infections. Nearly 10% of S brasiliensis infections involve the ocular adnexa, and Parinaud oculoglandular syndrome is commonly described in cases reported in Brazil.^42,43 Disseminated disease usually occurs in immunocompromised hosts; however, despite a focus on HIV co-infection,^8,44 prior epidemiologic research has suggested that diabetes and alcoholism are the most common predisposing factors.⁴⁵ Systemic disseminated sporotrichosis by definition affects at least 2 body systems, most commonly the central nervous system, lungs, and musculoskeletal system (including joints and bone marrow).⁴⁵

Extracutaneous sporotrichosis is rare and often is difficult to diagnose. Risk factors include chronic obstructive pulmonary disease, alcoholism, use of steroid medications, AIDS, solid organ transplantation, and use of tumor necrosis factor α inhibitors. It usually affects bony structures through hematogenous spread in immunocompromised hosts and is associated with a high risk for osteomyelitis due to delayed diagnosis.²

Clinical progression of sporotrichosis usually is slow, and lesions may persist for months or years if untreated. Sporotrichosis should always be considered for atypical, persistent, or treatment-resistant manifestations of nodular or ulcerated skin lesions in endemic regions or acute illness with these symptoms following exposure. Preventing secondary bacterial infection is an important consideration as it can exacerbate disease severity, extend the treatment duration, prolong hospitalization, and increase mortality risk.⁴⁶

Diagnosis

In regions endemic for S brasiliensis, it may be acceptable to commence treatment on clinical suspicion without a definitive diagnosis,²¹ but caution is necessary, as lesions easily can be mistaken for other conditions such as Mycobacterium marinum infections (sporotrichoid lesions) or cutaneous leishmaniasis. Limited availability of molecular diagnostic tools in routine clinical laboratories affects the diagnosis of sporotrichosis and species identification. Direct microscopy on a 10% to 30% potassium hydroxide wet mount has low diagnostic sensitivity and is not recommended⁴⁷; findings typically include cigar-shaped yeast cells (eFigure 1). Biopsy and histopathology also are useful, although in many infections (other than those due to S brasiliensis) there are very few detectable organisms in the tissue. Fluorescent staining of fungi with optical brighteners (eg, Calcofluor, Blankophor) is a useful technique with high sensitivity in clinical specimens on histopathologic and direct examination.⁴⁸

Fungal culture has higher sensitivity and specificity than microscopy and is the gold-standard approach for diagnosis of sporotrichosis (eFigure 2); however, culture cannot differentiate between Sporothrix species and may take more than a month to yield a positive result.⁷ No reliable serologic test for sporotrichosis has been validated, and a standardized antigen assay currently is unavailable.⁴⁹ Serology may be more useful for patients who present with systemic disease or have persistently negative culture results despite a high index of suspicion. 

A recent study evaluated the effectiveness of a lateral flow assay for detecting anti-Sporothrix antibodies, demonstrating the potential for its use as a rapid diagnostic test.⁵⁰ Investigating different molecular methods to increase the sensitivity and specificity of diagnosis and distinguish Sporothrix species has been a focus of recent research, with a preference for polymerase chain reaction (PCR)–based genotypic methods.^13,51 Recent advances in diagnostic testing include the development of multiplex PCR,⁵² culture-independent PCR techniques,⁵³ and matrix-assisted laser desorption/ionization–time of flight mass spectrometry,⁵⁴ each with varying clinical and practical applicability. Specialized testing can be beneficial for patients who have a poor therapeutic response to standard treatment, guide antifungal treatment choices, and identify epidemiologic disease and transmission patterns.²¹

Although rarely performed, antifungal susceptibility testing may be useful in guiding therapy to improve patient outcomes, particularly in the context of treatment failure, which has been documented with isolates exhibiting high minimal inhibitory concentrations (MICs) to first-line therapy and a poor clinical response.^55,56 Proposed mechanisms of resistance include increased cellular melanin ­production, which protects against oxidative stress and reduces antifungal activity.⁵⁶ Antifungal susceptibility profiles for therapeutics vary across Sporothrix species; for example, S brasiliensis generally shows lower MICs to itraconazole and terbinafine compared with S schenckii and S globosa, and S schenckii has shown a high MIC to itraconazole, as reflected in MIC distribution studies and epidemiologic cutoff values for antifungal agents.^55,57-59 However, specific breakpoints for different Sporothrix species have not been determined.⁶⁰ Robust clinical studies are needed to determine the correlation of in vitro MICs to clinical outcomes to assess the utility of antifungal susceptibility testing for Sporothrix species.

Management

Treatment of sporotrichosis is guided by clinical presentation, host immune status, and species identification. Management can be challenging in cases with an atypical or delayed diagnosis and limited access to molecular testing methods. Itraconazole is the first-line therapy for management of cutaneous sporotrichosis. It is regarded as safe, effective, well tolerated, and easily administered, with doses ranging from 100 mg in mild cases to 400 mg (with daily or twice-daily dosing).⁶¹ Treatment usually is for 3 to 6 months and should continue for 1 month after complete clinical resolution is achieved⁶²; however, some cases of S brasiliensis infection require longer treatment, and complex or disseminated cases may require therapy for up to 12 months.⁶¹ Itraconazole is contraindicated in pregnancy and has many drug interactions (through cytochrome P450 inhibition) that may preclude administration, particularly in elderly populations. Therapeutic drug monitoring is recommended for prolonged or high-dose therapy, with periodic liver function testing to reduce the risk for toxicity. Itraconazole should be administered with food, and concurrent use of antacids or proton pump inhibitors should be avoided.⁶¹

Oral terbinafine (250 mg daily) can be considered as an effective alternative to treat cutaneous disease.⁶³ Particularly in resource-limited settings, potassium iodide is an affordable and effective treatment for cutaneous sporotrichosis, administered as a saturated oral solution,⁶⁴ but due to adverse effects such as severe nausea, the daily dose should be increased slowly each day to ensure tolerance.

Amphotericin B is the treatment of choice for severe and treatment-resistant cases of sporotrichosis as well as for immunocompromised patients.^21,61 In patients with HIV, a longer treatment course is recommended with oversight from an infectious diseases specialist and usually is followed by a 12-month course of itraconazole after completion of initial therapy.⁶¹ Surgical excision infrequently is recommended but can be used in combination with another treatment modality and may be useful with a slow or incomplete response to medical therapy. Thermotherapy involves direct application of heat to cutaneous lesions and may be considered for small and localized lesions, particularly if antifungal agents are contraindicated or poorly tolerated.⁶¹ Public health measures include promoting case detection through practitioner education and patient awareness in endemic regions, as well as zoonotic control of infected animals to manage sporotrichosis.

Final Thoughts

Sporotrichosis is a fungal infection with growing public health significance. While the global disease burden is unknown, rising case numbers and geographic spread likely reflect a complex interaction between humans, the environment, and animals, exemplified by the spread of feline-associated infection due to S brasiliensis in South America.²⁸ Cases of S brasiliensis infection after importation of an affected cat have been detected outside South America, and clinicians should be alert for introduction to the United States. Strengthening genotypic and phenotypic diagnostic capabilities will allow species identification and guide treatment and management. Disease surveillance and operational research will inform public health approaches to control sporotrichosis worldwide.

Sporotrichosis is an implantation mycosis that classically manifests as a localized skin and subcutaneous fungal infection but may disseminate to other parts of the body.¹ It is caused by several species within the Sporothrix genus² and is associated with varying clinical manifestations, geographic distributions, virulence profiles, and antifungal susceptibility patterns.^3,4 Transmission of the fungus can involve inoculation from wild or domestic animals (eg, cats).^5,6 Occupations such as landscaping and gardening or elements in the environment (eg, soil, plant fragments) also can be sources of exposure.^7,8

Sporotrichosis is recognized by the World Health Organization as a neglected tropical disease that warrants global advocacy to prevent infections and improve patient outcomes.^9,10 It carries substantial stigma and socioeconomic burden.^11,12 Diagnostics, species identification, and antifungal susceptibility testing often are limited, particularly in resource-limited settings.¹³ In this article, we outline steps to diagnose and manage sporotrichosis to improve care for affected patients globally.

Epidemiology

Sporotrichosis occurs worldwide but is most common in tropical and subtropical regions.^14,15 Outbreaks and clusters of sporotrichosis have been observed across North, Central, and South America as well as in southern Africa and Asia. The estimated annual incidence is 40,000 cases worldwide,^16-20 but global case counts likely are underestimated due to limited surveillance data and diagnostic capability.²¹

On the Asian subcontinent, Sporothrix globosa is the predominant causative species of sporotrichosis, typically via contaminated plant material²²; however, at least 1 outbreak has been associated with severe flooding.²³ In Africa, infections are most commonly caused by Sporothrix schenckii sensu stricto through a similar transmission route. Across Central America, S schenckii sensu stricto is the predominant causative species; however, Sporothrix brasiliensis is the predominant species in some countries in South America, particularly Brazil.²⁰   

Data describing the current geographic distribution and prevalence of sporotrichosis in the United States are limited. Historically, the disease was reported most commonly in Midwestern states and was associated with outbreaks related to handling Sphagnum moss.^24,25 Epidemiologic studies using health insurance data indicate an average annual incidence of 2.0 cases per million individuals in the United States, with a higher prevalence among women and a median age at diagnosis of 54 years.²⁶ A review of sporotrichosis-associated hospitalizations across the United States from 2000 to 2013 indicated an average hospitalization rate of 0.35 cases per 1 million individuals; rates were higher (0.45 cases per million) in the West and lower (0.15 per million) in the Northeast and in men (0.40 per million).²⁷ Type 2 diabetes, immune-mediated inflammatory disease, and chronic obstructive pulmonary disease are associated with an increased risk for infection and hospitalization.²⁷

Causative Organisms

Sporothrix species are thermally dimorphic fungi that can grow as mold in the environment and as yeast in human tissue. Sporothrix brasiliensis is the only thermodimorphic fungus known to be transmitted directly in its yeast form.²⁸ In other species, inoculation usually occurs after contact with contaminated soil or plant material during gardening, carpentry, or agricultural practices.⁷

Zoonotic transmission of sporotrichosis from animals to humans has been reported from a range of domestic and wild animals and birds but historically has been rare.^5,7,29,30 Recently, the importance of both cat-to-cat (epizootic) and cat-to-human (zoonotic) transmission of S brasiliensis has been recognized, with infection typically following traumatic inoculation after a scratch or bite; less frequently, transmission occurs due to exposure to respiratory droplets or contact with feline exudates.^5,29,31Sporothrix brasiliensis is responsible for zoonotic epidemics in South America, primarily in Brazil. Transmission occurs among humans, cats, and canines, with felines serving as the primary vector.³² Transmission of this species is particularly common in stray and unneutered male cats that exhibit aggressive behaviors.³³ This species also is thought to be the most virulent Sporothrix species.²¹

Sporothrix brasiliensis can persist on nondisinfected inanimate surfaces, which suggests that fomite transmission can lead to human infection.³¹ The epidemiology of sporotrichosis has transformed in regions where S brasiliensis circulates, with epidemic spread resulting in thousands of cases, whereas in other areas without S brasilinesis, sporotrichosis predominantly occurs sporadically with rare clusters.^1,2,7,15

Sporotrichosis has been the subject of a taxonomic debate in the mycology community.²¹Sporothrix schenckii sensu lato originally was believed to be the sole fungal pathogen causing sporotrichosis³⁴ but was later divided into S schenckii sensu stricto, Sporothrix globosa, and S brasiliensis.³⁵ More than 60 distinct species now have been described within the Sporothrix genus,^36,37 but the primary species causing human sporotrichosis include S schenckii sensu stricto, S brasiliensis, S globosa, Sporothrix mexicana, and Sporothrix luriei.³⁵ Both S schenckii and S brasiliensis have greater virulence than other Sporothrix species⁴; however, S schenckii causes infections that typically are localized and are milder, while S brasiliensis can lead to more atypical, severe, and disseminated infections^38,39 and can spread epidemically.

Clinical Manifestations

Sporotrichosis has 4 main clinical presentations: cutaneous lymphatic, fixed cutaneous, cutaneous or systemic disseminated, and extracutaneous.^40,41 The most common clinical manifestation is the cutaneous lymphatic form, which predominantly affects the hands and forearms in adults and the face in children.⁷ The primary lesion usually manifests as a unilateral papule, nodule, or pustule that may ulcerate (sporotrichotic chancre), but multiple sites of inoculation are possible. Subsequent lesions may appear in a linear distribution along a regional lymphatic path (sporotrichoid spread). Systemic symptoms and regional lymphadenopathy are uncommon and usually are mild.

The second most common clinical manifestation is the fixed cutaneous form, typically affecting the face, neck, trunk, or legs with a single papule, nodule, or verrucous lesion with no lymphangitic spread.⁷ Usually confined to the inoculation site, the primary lesion may be accompanied by satellite lesions and often presents a diagnostic challenge.

Disseminated sporotrichosis (either cutaneous or systemic) is rare. Disseminated cutaneous sporotrichosis manifests with multiple noncontiguous skin lesions caused by lymphatic and possible hematogenous spread. Lesions may include a combination of papules, pustules, follicular eruptions, crusted plaques, and ulcers that may mimic other systemic infections. Immunoreactive changes such as erythema nodosum, erythema multiforme, or arthritis may accompany skin lesions, most commonly with S brasiliensis infections. Nearly 10% of S brasiliensis infections involve the ocular adnexa, and Parinaud oculoglandular syndrome is commonly described in cases reported in Brazil.^42,43 Disseminated disease usually occurs in immunocompromised hosts; however, despite a focus on HIV co-infection,^8,44 prior epidemiologic research has suggested that diabetes and alcoholism are the most common predisposing factors.⁴⁵ Systemic disseminated sporotrichosis by definition affects at least 2 body systems, most commonly the central nervous system, lungs, and musculoskeletal system (including joints and bone marrow).⁴⁵

Extracutaneous sporotrichosis is rare and often is difficult to diagnose. Risk factors include chronic obstructive pulmonary disease, alcoholism, use of steroid medications, AIDS, solid organ transplantation, and use of tumor necrosis factor α inhibitors. It usually affects bony structures through hematogenous spread in immunocompromised hosts and is associated with a high risk for osteomyelitis due to delayed diagnosis.²

Clinical progression of sporotrichosis usually is slow, and lesions may persist for months or years if untreated. Sporotrichosis should always be considered for atypical, persistent, or treatment-resistant manifestations of nodular or ulcerated skin lesions in endemic regions or acute illness with these symptoms following exposure. Preventing secondary bacterial infection is an important consideration as it can exacerbate disease severity, extend the treatment duration, prolong hospitalization, and increase mortality risk.⁴⁶

Diagnosis

In regions endemic for S brasiliensis, it may be acceptable to commence treatment on clinical suspicion without a definitive diagnosis,²¹ but caution is necessary, as lesions easily can be mistaken for other conditions such as Mycobacterium marinum infections (sporotrichoid lesions) or cutaneous leishmaniasis. Limited availability of molecular diagnostic tools in routine clinical laboratories affects the diagnosis of sporotrichosis and species identification. Direct microscopy on a 10% to 30% potassium hydroxide wet mount has low diagnostic sensitivity and is not recommended⁴⁷; findings typically include cigar-shaped yeast cells (eFigure 1). Biopsy and histopathology also are useful, although in many infections (other than those due to S brasiliensis) there are very few detectable organisms in the tissue. Fluorescent staining of fungi with optical brighteners (eg, Calcofluor, Blankophor) is a useful technique with high sensitivity in clinical specimens on histopathologic and direct examination.⁴⁸

Fungal culture has higher sensitivity and specificity than microscopy and is the gold-standard approach for diagnosis of sporotrichosis (eFigure 2); however, culture cannot differentiate between Sporothrix species and may take more than a month to yield a positive result.⁷ No reliable serologic test for sporotrichosis has been validated, and a standardized antigen assay currently is unavailable.⁴⁹ Serology may be more useful for patients who present with systemic disease or have persistently negative culture results despite a high index of suspicion. 

A recent study evaluated the effectiveness of a lateral flow assay for detecting anti-Sporothrix antibodies, demonstrating the potential for its use as a rapid diagnostic test.⁵⁰ Investigating different molecular methods to increase the sensitivity and specificity of diagnosis and distinguish Sporothrix species has been a focus of recent research, with a preference for polymerase chain reaction (PCR)–based genotypic methods.^13,51 Recent advances in diagnostic testing include the development of multiplex PCR,⁵² culture-independent PCR techniques,⁵³ and matrix-assisted laser desorption/ionization–time of flight mass spectrometry,⁵⁴ each with varying clinical and practical applicability. Specialized testing can be beneficial for patients who have a poor therapeutic response to standard treatment, guide antifungal treatment choices, and identify epidemiologic disease and transmission patterns.²¹

Although rarely performed, antifungal susceptibility testing may be useful in guiding therapy to improve patient outcomes, particularly in the context of treatment failure, which has been documented with isolates exhibiting high minimal inhibitory concentrations (MICs) to first-line therapy and a poor clinical response.^55,56 Proposed mechanisms of resistance include increased cellular melanin ­production, which protects against oxidative stress and reduces antifungal activity.⁵⁶ Antifungal susceptibility profiles for therapeutics vary across Sporothrix species; for example, S brasiliensis generally shows lower MICs to itraconazole and terbinafine compared with S schenckii and S globosa, and S schenckii has shown a high MIC to itraconazole, as reflected in MIC distribution studies and epidemiologic cutoff values for antifungal agents.^55,57-59 However, specific breakpoints for different Sporothrix species have not been determined.⁶⁰ Robust clinical studies are needed to determine the correlation of in vitro MICs to clinical outcomes to assess the utility of antifungal susceptibility testing for Sporothrix species.

Management

Treatment of sporotrichosis is guided by clinical presentation, host immune status, and species identification. Management can be challenging in cases with an atypical or delayed diagnosis and limited access to molecular testing methods. Itraconazole is the first-line therapy for management of cutaneous sporotrichosis. It is regarded as safe, effective, well tolerated, and easily administered, with doses ranging from 100 mg in mild cases to 400 mg (with daily or twice-daily dosing).⁶¹ Treatment usually is for 3 to 6 months and should continue for 1 month after complete clinical resolution is achieved⁶²; however, some cases of S brasiliensis infection require longer treatment, and complex or disseminated cases may require therapy for up to 12 months.⁶¹ Itraconazole is contraindicated in pregnancy and has many drug interactions (through cytochrome P450 inhibition) that may preclude administration, particularly in elderly populations. Therapeutic drug monitoring is recommended for prolonged or high-dose therapy, with periodic liver function testing to reduce the risk for toxicity. Itraconazole should be administered with food, and concurrent use of antacids or proton pump inhibitors should be avoided.⁶¹

Oral terbinafine (250 mg daily) can be considered as an effective alternative to treat cutaneous disease.⁶³ Particularly in resource-limited settings, potassium iodide is an affordable and effective treatment for cutaneous sporotrichosis, administered as a saturated oral solution,⁶⁴ but due to adverse effects such as severe nausea, the daily dose should be increased slowly each day to ensure tolerance.

Amphotericin B is the treatment of choice for severe and treatment-resistant cases of sporotrichosis as well as for immunocompromised patients.^21,61 In patients with HIV, a longer treatment course is recommended with oversight from an infectious diseases specialist and usually is followed by a 12-month course of itraconazole after completion of initial therapy.⁶¹ Surgical excision infrequently is recommended but can be used in combination with another treatment modality and may be useful with a slow or incomplete response to medical therapy. Thermotherapy involves direct application of heat to cutaneous lesions and may be considered for small and localized lesions, particularly if antifungal agents are contraindicated or poorly tolerated.⁶¹ Public health measures include promoting case detection through practitioner education and patient awareness in endemic regions, as well as zoonotic control of infected animals to manage sporotrichosis.

Final Thoughts

Sporotrichosis is a fungal infection with growing public health significance. While the global disease burden is unknown, rising case numbers and geographic spread likely reflect a complex interaction between humans, the environment, and animals, exemplified by the spread of feline-associated infection due to S brasiliensis in South America.²⁸ Cases of S brasiliensis infection after importation of an affected cat have been detected outside South America, and clinicians should be alert for introduction to the United States. Strengthening genotypic and phenotypic diagnostic capabilities will allow species identification and guide treatment and management. Disease surveillance and operational research will inform public health approaches to control sporotrichosis worldwide.

The American Contact Dermatitis Society selected toluene-2,5-diamine sulfate (PTDS) as the 2025 Allergen of the Year.¹ Widely used as an alternative to para-phenylenediamine (PPD) in oxidative and permanent/semipermanent hair dyes, PTDS has emerged as a potent contact allergen with substantial cross-­reactivity to PPD. In this article, we discuss PTDS as both a PPD alternative and a contact allergen as well as the clinical features of allergic contact dermatitis (ACD) to PTDS and practical recommendations for management in at-risk populations.

Background

Toluene-2,5-diamine sulfate is a compound formed by combining 2,5-diaminotoluene (PTD) with sulfuric acid, making it more water soluble and potentially less irritating than PTD alone.² In this article, the terms PTDS and PTD will be used interchangeably due to their structural similarity.

Toluene-2,5-diamine sulfate commonly is used in oxidative and permanent/semipermanent hair dyes as an alternative to PPD, the most common hair dye contact allergen.³ Toluene-2,5-diamine sulfate also is a component used in color photography development and in dyes used for textiles, furs, leathers, and biologic stains.⁴ The prevalence of PTDS contact allergy likely is underreported due to its absence in routine patch test series such as the Thin-Layer Rapid Use Epicutaneous (T.R.U.E.) test (Smart Practice) and the American Contact Dermatitis Society Core 90 Series.

Cross-Reactivity Between PTDS and PPD

There is substantial cross-reactivity between PTDS and PPD, necessitating careful avoidance and alternative dye selection. The rate of cross-reactivity between these compounds is high, with some estimated to be more than 80% among patch tested individuals.^5-9 In some cases, patients with a contact allergy to PPD are able to tolerate dyes containing PTDS. Studies conducted in Canada and Europe showed that 31.3% to 76.3% of patients with a contact allergy to PPD also had an allergy to PTDS or PTD.^7,8,10 Stronger reactions to PPD also seem to be associated with an increased risk for cross-reaction.¹¹

Clinical Manifestation of ACD to PTDS

In the literature, case reports of ACD caused by PTDS are rare. The clinical manifestations of PTDS-ACD will closely mirror those described in PPD-ACD or PTD-ACD, reflecting the cross-reactivity between these aromatic amines. Generally, ACD to components in hair dyes manifests as a pruritic, erythematous, edematous, eczematous rash that can affect the margins of the scalp, ears, face, and/or neck. Severe cases can extend beyond the initial area of contact, potentially resulting in widespread involvement and systemic symptoms.¹² Notably, the scalp often is spared, which may be attributable to protection provided by sebum or the hair itself covering the scalp.¹³

Two case reports described ACD of the eyebrows after application of PTD-containing hair dye.^14,15 One patient developed severe bullous ACD involving the eyebrows and eyelashes with concurrent conjunctivitis,¹⁴ and the other experienced erythema, edema, burning, itching, and exudation at and around the eyebrows.¹⁵ The latter patient had prior exposure to PPD from a black henna tattoo, which may have led to an initial sensitization and subsequent cross-reactivity to PTD in the hair dye. 

Another case report described a patient with erythema, edema, and scaling of the face, neck, and arms within 1 week of exposure to a new hair dye at a salon.¹⁶ Patch testing revealed a positive reaction to PPD on day 3, despite it not being a component of the hair dye. On day 7, the patient showed a delayed reaction to PTD, which was confirmed to be present in the dye.¹⁶ The implications of these findings are twofold. First, delayed patch test readings beyond day 5 could provide more sensitive interpretation. Second, this case highlights the cross-reactivity between these related compounds. 

Hairdressers and users of hair care products are most commonly affected by PTDS contact allergy. Though hairdressers generally are at a higher risk, prevalence for PTD sensitization in a European patch tested population showed rates of 20% in hairdressers and 30.8% in consumers.¹⁷ The North American Contact Dermatitis Group reported PTDS sensitization in fewer than 2% of 4121 patients patch tested across 13 North American centers over a period of 1 year.¹⁸ This suggests potential underutilization of the more specific panels that include PTDS. 

Hairdressers are at an increased risk of contact allergy to PTDS due to occupational exposure and are at higher risk for hand dermatitis due to frequent exposure to water. In a review of epidemiologic studies published between 2000 and 2021, the pooled lifetime prevalence of hand eczema in hairdressers was 38.2% compared to an estimated lifetime prevalence of 14.5% in the general population.¹⁹ Higher risk for hand eczema can increase the risk for sensitization to contact allergens including PPD and PTDS due to impaired barrier function, allowing allergen penetration through disrupted skin.²⁰

Strategies for Management and Avoidance

Patients with suspected contact allergy to PTDS should avoid this compound and related dye chemicals such as PPD due to the high risk for ACD and frequent cross-reactivity. While PTDS-allergic patients should avoid products containing PPD, some patients allergic to PPD may be able to tolerate exposure to PTD or PTDS.^7,8,10 Regardless, any suspected contact allergy should be supported by patch testing with PTDS and PPD to confirm sensitization. Patch test readings for PTDS/PTD could be delayed beyond day 5 if clinical suspicion is high and early patch test reading is noncontributory; however, more studies are needed to establish that later readings are more reliable for PTDS.

Occupational risk reduction in hairdressers is essential. Hairdressers as well as at-home users of hair dyes should be properly informed by their dermatologist or other trained health care professional about PTDS and PTD as potent allergens and should be provided with information on potential alternatives. They also should be counseled on proper skin protection, including single-use gloves and careful hand care through gentle cleansing and use of barrier creams to protect skin integrity and prevent contact dermatitis. Nitrile rubber gloves offer the best protection when handling hair dyes. Polyvinyl chloride or natural latex rubber gloves also may be sufficient; however, polyethylene gloves should be avoided, as they have been shown to have the fastest time to penetration.²¹ Gloves should be properly sized, and reuse should be avoided. 

Because PTDS and PTD frequently are used in semipermanent and permanent hair dyes, temporary hair dyes (eg, henna-based dyes) may be safer alternatives, as they infrequently contain these allergens. Food, Drug, and Cosmetics (FD&C) and Drug and Cosmetics (D&C) dyes also are used in some semipermanent hair dyes and seem to have low cross-reactivity to PPD; therefore, these may be used in patients allergic to PTDS or PTD.²² However, these dyes require frequent reapplication, which may be unfavorable to some patients. Gallic acid–based hair dyes have been shown to be safe alternatives in patients with contact allergy to PTDS or PTD, though pretesting is recommended with a repeat open application test.²³ The PPD derivative 2-methoxymethyl-para-phenylenediamine (ME-PPD) has reduced sensitization potential. In simulated hair dye use conditions, cross-reactivity to ME-PPD in patients with PPD contact allergy was 30% compared with 84% for PPD.²⁴ However, in an open-use test in 25 PPD-allergic individuals, ME-PPD was reactive in 84% (21/25) and ME-PPD 2% patch testing was positive in 48% (12/25), suggesting that ME-PPD could be a potential alternative but is not universally tolerated.²⁵

It is important to note that products purporting to be natural or botanical are not inherently safe and may themselves be allergenic.²⁵ Patients should attempt a repeat open application test or patch testing prior to use of an alternative dye.

Given the prevalence of PTDS allergy, the fact that some PPD-allergic individuals may be able to tolerate hair dyes containing PTDS (assuming it tests negative), and the substantial quality of life and socioeconomic impacts of hair dye allergy, PTDS should be considered as an addition to standard patch test screening series.¹

Final Thoughts

While initially popularized as an alternative to PPD in semipermanent and permanent hair dyes, PTDS now is emerging as a contact allergen with well-documented cross-reactivity to PPD. Dermatologists should consider patch testing for PTDS (and PPD) in individuals who regularly encounter this compound. This will guide further counseling and recommendations.

The American Contact Dermatitis Society selected toluene-2,5-diamine sulfate (PTDS) as the 2025 Allergen of the Year.¹ Widely used as an alternative to para-phenylenediamine (PPD) in oxidative and permanent/semipermanent hair dyes, PTDS has emerged as a potent contact allergen with substantial cross-­reactivity to PPD. In this article, we discuss PTDS as both a PPD alternative and a contact allergen as well as the clinical features of allergic contact dermatitis (ACD) to PTDS and practical recommendations for management in at-risk populations.

Background

Toluene-2,5-diamine sulfate is a compound formed by combining 2,5-diaminotoluene (PTD) with sulfuric acid, making it more water soluble and potentially less irritating than PTD alone.² In this article, the terms PTDS and PTD will be used interchangeably due to their structural similarity.

Toluene-2,5-diamine sulfate commonly is used in oxidative and permanent/semipermanent hair dyes as an alternative to PPD, the most common hair dye contact allergen.³ Toluene-2,5-diamine sulfate also is a component used in color photography development and in dyes used for textiles, furs, leathers, and biologic stains.⁴ The prevalence of PTDS contact allergy likely is underreported due to its absence in routine patch test series such as the Thin-Layer Rapid Use Epicutaneous (T.R.U.E.) test (Smart Practice) and the American Contact Dermatitis Society Core 90 Series.

Cross-Reactivity Between PTDS and PPD

There is substantial cross-reactivity between PTDS and PPD, necessitating careful avoidance and alternative dye selection. The rate of cross-reactivity between these compounds is high, with some estimated to be more than 80% among patch tested individuals.^5-9 In some cases, patients with a contact allergy to PPD are able to tolerate dyes containing PTDS. Studies conducted in Canada and Europe showed that 31.3% to 76.3% of patients with a contact allergy to PPD also had an allergy to PTDS or PTD.^7,8,10 Stronger reactions to PPD also seem to be associated with an increased risk for cross-reaction.¹¹

Clinical Manifestation of ACD to PTDS

In the literature, case reports of ACD caused by PTDS are rare. The clinical manifestations of PTDS-ACD will closely mirror those described in PPD-ACD or PTD-ACD, reflecting the cross-reactivity between these aromatic amines. Generally, ACD to components in hair dyes manifests as a pruritic, erythematous, edematous, eczematous rash that can affect the margins of the scalp, ears, face, and/or neck. Severe cases can extend beyond the initial area of contact, potentially resulting in widespread involvement and systemic symptoms.¹² Notably, the scalp often is spared, which may be attributable to protection provided by sebum or the hair itself covering the scalp.¹³

Two case reports described ACD of the eyebrows after application of PTD-containing hair dye.^14,15 One patient developed severe bullous ACD involving the eyebrows and eyelashes with concurrent conjunctivitis,¹⁴ and the other experienced erythema, edema, burning, itching, and exudation at and around the eyebrows.¹⁵ The latter patient had prior exposure to PPD from a black henna tattoo, which may have led to an initial sensitization and subsequent cross-reactivity to PTD in the hair dye. 

Another case report described a patient with erythema, edema, and scaling of the face, neck, and arms within 1 week of exposure to a new hair dye at a salon.¹⁶ Patch testing revealed a positive reaction to PPD on day 3, despite it not being a component of the hair dye. On day 7, the patient showed a delayed reaction to PTD, which was confirmed to be present in the dye.¹⁶ The implications of these findings are twofold. First, delayed patch test readings beyond day 5 could provide more sensitive interpretation. Second, this case highlights the cross-reactivity between these related compounds. 

Hairdressers and users of hair care products are most commonly affected by PTDS contact allergy. Though hairdressers generally are at a higher risk, prevalence for PTD sensitization in a European patch tested population showed rates of 20% in hairdressers and 30.8% in consumers.¹⁷ The North American Contact Dermatitis Group reported PTDS sensitization in fewer than 2% of 4121 patients patch tested across 13 North American centers over a period of 1 year.¹⁸ This suggests potential underutilization of the more specific panels that include PTDS. 

Hairdressers are at an increased risk of contact allergy to PTDS due to occupational exposure and are at higher risk for hand dermatitis due to frequent exposure to water. In a review of epidemiologic studies published between 2000 and 2021, the pooled lifetime prevalence of hand eczema in hairdressers was 38.2% compared to an estimated lifetime prevalence of 14.5% in the general population.¹⁹ Higher risk for hand eczema can increase the risk for sensitization to contact allergens including PPD and PTDS due to impaired barrier function, allowing allergen penetration through disrupted skin.²⁰

Strategies for Management and Avoidance

Patients with suspected contact allergy to PTDS should avoid this compound and related dye chemicals such as PPD due to the high risk for ACD and frequent cross-reactivity. While PTDS-allergic patients should avoid products containing PPD, some patients allergic to PPD may be able to tolerate exposure to PTD or PTDS.^7,8,10 Regardless, any suspected contact allergy should be supported by patch testing with PTDS and PPD to confirm sensitization. Patch test readings for PTDS/PTD could be delayed beyond day 5 if clinical suspicion is high and early patch test reading is noncontributory; however, more studies are needed to establish that later readings are more reliable for PTDS.

Occupational risk reduction in hairdressers is essential. Hairdressers as well as at-home users of hair dyes should be properly informed by their dermatologist or other trained health care professional about PTDS and PTD as potent allergens and should be provided with information on potential alternatives. They also should be counseled on proper skin protection, including single-use gloves and careful hand care through gentle cleansing and use of barrier creams to protect skin integrity and prevent contact dermatitis. Nitrile rubber gloves offer the best protection when handling hair dyes. Polyvinyl chloride or natural latex rubber gloves also may be sufficient; however, polyethylene gloves should be avoided, as they have been shown to have the fastest time to penetration.²¹ Gloves should be properly sized, and reuse should be avoided. 

Because PTDS and PTD frequently are used in semipermanent and permanent hair dyes, temporary hair dyes (eg, henna-based dyes) may be safer alternatives, as they infrequently contain these allergens. Food, Drug, and Cosmetics (FD&C) and Drug and Cosmetics (D&C) dyes also are used in some semipermanent hair dyes and seem to have low cross-reactivity to PPD; therefore, these may be used in patients allergic to PTDS or PTD.²² However, these dyes require frequent reapplication, which may be unfavorable to some patients. Gallic acid–based hair dyes have been shown to be safe alternatives in patients with contact allergy to PTDS or PTD, though pretesting is recommended with a repeat open application test.²³ The PPD derivative 2-methoxymethyl-para-phenylenediamine (ME-PPD) has reduced sensitization potential. In simulated hair dye use conditions, cross-reactivity to ME-PPD in patients with PPD contact allergy was 30% compared with 84% for PPD.²⁴ However, in an open-use test in 25 PPD-allergic individuals, ME-PPD was reactive in 84% (21/25) and ME-PPD 2% patch testing was positive in 48% (12/25), suggesting that ME-PPD could be a potential alternative but is not universally tolerated.²⁵

It is important to note that products purporting to be natural or botanical are not inherently safe and may themselves be allergenic.²⁵ Patients should attempt a repeat open application test or patch testing prior to use of an alternative dye.

Given the prevalence of PTDS allergy, the fact that some PPD-allergic individuals may be able to tolerate hair dyes containing PTDS (assuming it tests negative), and the substantial quality of life and socioeconomic impacts of hair dye allergy, PTDS should be considered as an addition to standard patch test screening series.¹

Final Thoughts

While initially popularized as an alternative to PPD in semipermanent and permanent hair dyes, PTDS now is emerging as a contact allergen with well-documented cross-reactivity to PPD. Dermatologists should consider patch testing for PTDS (and PPD) in individuals who regularly encounter this compound. This will guide further counseling and recommendations.

The American Contact Dermatitis Society selected toluene-2,5-diamine sulfate (PTDS) as the 2025 Allergen of the Year.¹ Widely used as an alternative to para-phenylenediamine (PPD) in oxidative and permanent/semipermanent hair dyes, PTDS has emerged as a potent contact allergen with substantial cross-­reactivity to PPD. In this article, we discuss PTDS as both a PPD alternative and a contact allergen as well as the clinical features of allergic contact dermatitis (ACD) to PTDS and practical recommendations for management in at-risk populations.

Background

Toluene-2,5-diamine sulfate is a compound formed by combining 2,5-diaminotoluene (PTD) with sulfuric acid, making it more water soluble and potentially less irritating than PTD alone.² In this article, the terms PTDS and PTD will be used interchangeably due to their structural similarity.

Toluene-2,5-diamine sulfate commonly is used in oxidative and permanent/semipermanent hair dyes as an alternative to PPD, the most common hair dye contact allergen.³ Toluene-2,5-diamine sulfate also is a component used in color photography development and in dyes used for textiles, furs, leathers, and biologic stains.⁴ The prevalence of PTDS contact allergy likely is underreported due to its absence in routine patch test series such as the Thin-Layer Rapid Use Epicutaneous (T.R.U.E.) test (Smart Practice) and the American Contact Dermatitis Society Core 90 Series.

Cross-Reactivity Between PTDS and PPD

There is substantial cross-reactivity between PTDS and PPD, necessitating careful avoidance and alternative dye selection. The rate of cross-reactivity between these compounds is high, with some estimated to be more than 80% among patch tested individuals.^5-9 In some cases, patients with a contact allergy to PPD are able to tolerate dyes containing PTDS. Studies conducted in Canada and Europe showed that 31.3% to 76.3% of patients with a contact allergy to PPD also had an allergy to PTDS or PTD.^7,8,10 Stronger reactions to PPD also seem to be associated with an increased risk for cross-reaction.¹¹

Clinical Manifestation of ACD to PTDS

In the literature, case reports of ACD caused by PTDS are rare. The clinical manifestations of PTDS-ACD will closely mirror those described in PPD-ACD or PTD-ACD, reflecting the cross-reactivity between these aromatic amines. Generally, ACD to components in hair dyes manifests as a pruritic, erythematous, edematous, eczematous rash that can affect the margins of the scalp, ears, face, and/or neck. Severe cases can extend beyond the initial area of contact, potentially resulting in widespread involvement and systemic symptoms.¹² Notably, the scalp often is spared, which may be attributable to protection provided by sebum or the hair itself covering the scalp.¹³

Two case reports described ACD of the eyebrows after application of PTD-containing hair dye.^14,15 One patient developed severe bullous ACD involving the eyebrows and eyelashes with concurrent conjunctivitis,¹⁴ and the other experienced erythema, edema, burning, itching, and exudation at and around the eyebrows.¹⁵ The latter patient had prior exposure to PPD from a black henna tattoo, which may have led to an initial sensitization and subsequent cross-reactivity to PTD in the hair dye. 

Another case report described a patient with erythema, edema, and scaling of the face, neck, and arms within 1 week of exposure to a new hair dye at a salon.¹⁶ Patch testing revealed a positive reaction to PPD on day 3, despite it not being a component of the hair dye. On day 7, the patient showed a delayed reaction to PTD, which was confirmed to be present in the dye.¹⁶ The implications of these findings are twofold. First, delayed patch test readings beyond day 5 could provide more sensitive interpretation. Second, this case highlights the cross-reactivity between these related compounds. 

Hairdressers and users of hair care products are most commonly affected by PTDS contact allergy. Though hairdressers generally are at a higher risk, prevalence for PTD sensitization in a European patch tested population showed rates of 20% in hairdressers and 30.8% in consumers.¹⁷ The North American Contact Dermatitis Group reported PTDS sensitization in fewer than 2% of 4121 patients patch tested across 13 North American centers over a period of 1 year.¹⁸ This suggests potential underutilization of the more specific panels that include PTDS. 

Hairdressers are at an increased risk of contact allergy to PTDS due to occupational exposure and are at higher risk for hand dermatitis due to frequent exposure to water. In a review of epidemiologic studies published between 2000 and 2021, the pooled lifetime prevalence of hand eczema in hairdressers was 38.2% compared to an estimated lifetime prevalence of 14.5% in the general population.¹⁹ Higher risk for hand eczema can increase the risk for sensitization to contact allergens including PPD and PTDS due to impaired barrier function, allowing allergen penetration through disrupted skin.²⁰

Strategies for Management and Avoidance

Patients with suspected contact allergy to PTDS should avoid this compound and related dye chemicals such as PPD due to the high risk for ACD and frequent cross-reactivity. While PTDS-allergic patients should avoid products containing PPD, some patients allergic to PPD may be able to tolerate exposure to PTD or PTDS.^7,8,10 Regardless, any suspected contact allergy should be supported by patch testing with PTDS and PPD to confirm sensitization. Patch test readings for PTDS/PTD could be delayed beyond day 5 if clinical suspicion is high and early patch test reading is noncontributory; however, more studies are needed to establish that later readings are more reliable for PTDS.

Occupational risk reduction in hairdressers is essential. Hairdressers as well as at-home users of hair dyes should be properly informed by their dermatologist or other trained health care professional about PTDS and PTD as potent allergens and should be provided with information on potential alternatives. They also should be counseled on proper skin protection, including single-use gloves and careful hand care through gentle cleansing and use of barrier creams to protect skin integrity and prevent contact dermatitis. Nitrile rubber gloves offer the best protection when handling hair dyes. Polyvinyl chloride or natural latex rubber gloves also may be sufficient; however, polyethylene gloves should be avoided, as they have been shown to have the fastest time to penetration.²¹ Gloves should be properly sized, and reuse should be avoided. 

Because PTDS and PTD frequently are used in semipermanent and permanent hair dyes, temporary hair dyes (eg, henna-based dyes) may be safer alternatives, as they infrequently contain these allergens. Food, Drug, and Cosmetics (FD&C) and Drug and Cosmetics (D&C) dyes also are used in some semipermanent hair dyes and seem to have low cross-reactivity to PPD; therefore, these may be used in patients allergic to PTDS or PTD.²² However, these dyes require frequent reapplication, which may be unfavorable to some patients. Gallic acid–based hair dyes have been shown to be safe alternatives in patients with contact allergy to PTDS or PTD, though pretesting is recommended with a repeat open application test.²³ The PPD derivative 2-methoxymethyl-para-phenylenediamine (ME-PPD) has reduced sensitization potential. In simulated hair dye use conditions, cross-reactivity to ME-PPD in patients with PPD contact allergy was 30% compared with 84% for PPD.²⁴ However, in an open-use test in 25 PPD-allergic individuals, ME-PPD was reactive in 84% (21/25) and ME-PPD 2% patch testing was positive in 48% (12/25), suggesting that ME-PPD could be a potential alternative but is not universally tolerated.²⁵

It is important to note that products purporting to be natural or botanical are not inherently safe and may themselves be allergenic.²⁵ Patients should attempt a repeat open application test or patch testing prior to use of an alternative dye.

Given the prevalence of PTDS allergy, the fact that some PPD-allergic individuals may be able to tolerate hair dyes containing PTDS (assuming it tests negative), and the substantial quality of life and socioeconomic impacts of hair dye allergy, PTDS should be considered as an addition to standard patch test screening series.¹

Final Thoughts

While initially popularized as an alternative to PPD in semipermanent and permanent hair dyes, PTDS now is emerging as a contact allergen with well-documented cross-reactivity to PPD. Dermatologists should consider patch testing for PTDS (and PPD) in individuals who regularly encounter this compound. This will guide further counseling and recommendations.

Synthetic hair extensions are made from various plastic polymers (eg, modacrylic, vinyl chloride, and acrylonitrile) shaped into thin strands that mimic human hair and are used to add fullness, length, and manageability in individuals with textured hair.^1-3 The plastic polymers used to make synthetic hair, most notably acrylonitrile and vinyl chloride, are known to be toxic to humans.^1-4 The US Environmental Protection Agency classifies acrylonitrile as a probable carcinogen, and vinyl chloride is associated with the development of lymphoma; leukemia; and rare malignancies of the brain, liver, and lungs.^1,4 According to the Occupational Safety and Health Administration, the maximum exposure limits of vinyl chloride and acrylonitrile vapor or gas over an 8-hour period are 1 ppm (0.001 g/L) and 2 ppm (0.002 g/L), respectively.⁵ Exposure levels from wearing synthetic hair extensions easily exceed these maximums; for example, a full head of braids requires application of multiple packets of synthetic hair, resulting in continuous exposure to carcinogenic materials that can last for weeks to months at a time.¹ Furthermore, individuals as young as 3 years old can begin to style their hair with synthetic extensions, which not only leads to potentially harmful carcinogenic exposure in young children but also yields notably high levels of lifetime exposure in individuals who regularly style their hair with these products.

There currently are no regulations barring the use of potentially harmful materials from the manufacturing process for synthetic hair extensions.¹ As a result, rinsing with apple cider vinegar (ACV) is a popular remedy that many users claim can effectively remove harmful chemicals from synthetic hair.^6,7 As this is the only known remedy that aims to address this issue, we conducted a literature review of studies investigating the effects of the ACV rinse on the carcinogenicity of synthetic hair extensions.

Methods

We conducted a search of Google Scholar, JSTOR, Science Direct, the Public Library of Science, and PubMed articles indexed for MEDLINE using the terms ACV, apple cider vinegar rinse, ACV rinse, synthetic hair carcinogens, synthetic fiber carcinogens, synthetic hair extension carcinogens, modacrylic fibers, Kanekalon (a flame-retardant modacrylic fiber), acrylonitrile, and vinyl chloride fibers to identify primary research articles investigating the effects of the ACV rinse on the carcinogenicity of synthetic hair extensions for inclusion in our review. To broaden our search, we did not establish a time frame for publication of the articles included in the study. Articles investigating the ACV rinse that were unrelated to carcinogenicity and synthetic hair extensions were excluded from this study.

Results

Our initial literature search identified 270 articles, which decreased to 180 after removal of duplicates. These 180 articles were screened for relevance based on title and abstract, which yielded 6 articles. None of the 6 articles identified through our literature search discussed synthetic hair and carcinogenicity in the context of the ACV rinse and were subsequently excluded from our review (eFigure 1).

Comment

Potentially harmful chemicals and ingredients in hair care products marketed for textured hair are now established topics in public discourse among those familiar with textured hair care and maintenance^1,8; however, the discourse remains limited. Our search for scientific articles investigating the effects of the ACV rinse on the carcinogenicity of synthetic hair extensions revealed a notable deficit in the literature regarding scientific studies assessing this practice. While the likelihood that the ACV rinse effectively alters the carcinogenicity of plastic polymers found in synthetic hair extensions and improves their safety seems improbable, the deficit of empirical data evaluating this practice is concerning given both the prevalence of this remedy and the sizable demographic of patients who practice styling with synthetic hair.¹ Of the potential adverse outcomes (eg, contact dermatitis, traction alopecia) that are possible from styling with synthetic hair that have been reported in the literature, carcinogenic exposure from synthetic hair extensions is relatively absent, with the exception of a few publications,^2,3,9 despite its potential to cause serious long-term consequences for hair stylists and those who regularly use these products.

Interestingly, individuals who style their hair with synthetic hair extensions frequently tout the efficacy of the ACV rinse for removal of mostly unidentified irritants, although the effects are unverified.^6,7 While the ACV rinse may be an effective means of removing toxic chemicals from synthetic hair extensions, without verifiable data this method remains an unproven remedy whose perceived benefits could result from factors unrelated to the rinse itself. Theoretically, simply rinsing synthetic hair extensions with plain water prior to use may demonstrate similar efficacy to that of the ACV rinse. 

An additional factor worth mentioning is the lack of government regulations concerning the manufacturing practices of synthetic hair extensions. Flame-retardant materials such as trichloroethylene, polyvinyl chloride, and hexabromocyclododecane frequently are used in synthetic hair extensions despite their known adverse effects, which include reproductive organ toxicity and links to various cancers, leading to them being banned in 5 states.^1,10-12 With no federal ban on these materials, individuals using synthetic hair remain at risk.  

It is unclear what chemicals, irritants, or toxic substances the ACV rinse method could potentially remove from synthetic hair. In general, manufacturers of synthetic hair extensions are not forthcoming with information regarding materials used in the processing of their products despite public inquiries into their manufacturing practices.⁶ Although Whitehurst’s³ curriculum details the process of making synthetic polymer fibers, the overall processes by which these plastics are made to resemble human hair have not been reviewed in academic publications. Should this information be made available to the public, consumers could potentially avoid specific irritants when purchasing synthetic hair extensions.   

The most common management strategy observed in the literature for adverse outcomes attributable to synthetic hair is discontinuation of use²; however, the prevalence and cultural significance of styling with synthetic hair extensions, along with the convenience these styles offer, make this option suboptimal. The scarcity of publications concerning the management of adverse outcomes related to the use of synthetic hair extensions may explain the absence of alternative management recommendations in the literature. Notably, new synthetic hair extensions from manufacturers that exclude plastic polymers and other harmful additives are now available to the public¹³; however, these hair extensions are cost prohibitive and are less accessible compared to synthetic extensions made from modacrylic fibers (eFigures 2 and 3).^1,13-16 

Final Thoughts

The ACV rinse method is an anecdotal remedy for reducing the harm and risk of adverse outcomes and complications associated with synthetic hair extensions. Discontinued use of these components is the only remedy provided within academic literature to address the harmful ingredients found in synthetic hair extensions.² Presently, there are no known data that support or disprove the efficacy of the ACV rinse. Furthermore, no academic guidance specifically supports remedies for mitigating carcinogen exposure risks in patients who style their hair with synthetic extensions. Given the early onset of exposure to synthetic hair in pediatric populations and the substantial demographic utilizing hairstyles that incorporate synthetic hair extensions, concerns regarding potential exposure risks cannot be overstated. Dermatologists should inform their patients of the potential risks associated with styling with synthetic hair extensions, helping them make informed decisions about future styling habits and hair care choices. Lastly, future studies should investigate how, if at all, ACV rinses alter what are arguably the most harmful components of synthetic hair extensions.

Synthetic hair extensions are made from various plastic polymers (eg, modacrylic, vinyl chloride, and acrylonitrile) shaped into thin strands that mimic human hair and are used to add fullness, length, and manageability in individuals with textured hair.^1-3 The plastic polymers used to make synthetic hair, most notably acrylonitrile and vinyl chloride, are known to be toxic to humans.^1-4 The US Environmental Protection Agency classifies acrylonitrile as a probable carcinogen, and vinyl chloride is associated with the development of lymphoma; leukemia; and rare malignancies of the brain, liver, and lungs.^1,4 According to the Occupational Safety and Health Administration, the maximum exposure limits of vinyl chloride and acrylonitrile vapor or gas over an 8-hour period are 1 ppm (0.001 g/L) and 2 ppm (0.002 g/L), respectively.⁵ Exposure levels from wearing synthetic hair extensions easily exceed these maximums; for example, a full head of braids requires application of multiple packets of synthetic hair, resulting in continuous exposure to carcinogenic materials that can last for weeks to months at a time.¹ Furthermore, individuals as young as 3 years old can begin to style their hair with synthetic extensions, which not only leads to potentially harmful carcinogenic exposure in young children but also yields notably high levels of lifetime exposure in individuals who regularly style their hair with these products.

There currently are no regulations barring the use of potentially harmful materials from the manufacturing process for synthetic hair extensions.¹ As a result, rinsing with apple cider vinegar (ACV) is a popular remedy that many users claim can effectively remove harmful chemicals from synthetic hair.^6,7 As this is the only known remedy that aims to address this issue, we conducted a literature review of studies investigating the effects of the ACV rinse on the carcinogenicity of synthetic hair extensions.

Methods

We conducted a search of Google Scholar, JSTOR, Science Direct, the Public Library of Science, and PubMed articles indexed for MEDLINE using the terms ACV, apple cider vinegar rinse, ACV rinse, synthetic hair carcinogens, synthetic fiber carcinogens, synthetic hair extension carcinogens, modacrylic fibers, Kanekalon (a flame-retardant modacrylic fiber), acrylonitrile, and vinyl chloride fibers to identify primary research articles investigating the effects of the ACV rinse on the carcinogenicity of synthetic hair extensions for inclusion in our review. To broaden our search, we did not establish a time frame for publication of the articles included in the study. Articles investigating the ACV rinse that were unrelated to carcinogenicity and synthetic hair extensions were excluded from this study.

Results

Our initial literature search identified 270 articles, which decreased to 180 after removal of duplicates. These 180 articles were screened for relevance based on title and abstract, which yielded 6 articles. None of the 6 articles identified through our literature search discussed synthetic hair and carcinogenicity in the context of the ACV rinse and were subsequently excluded from our review (eFigure 1).

Comment

Potentially harmful chemicals and ingredients in hair care products marketed for textured hair are now established topics in public discourse among those familiar with textured hair care and maintenance^1,8; however, the discourse remains limited. Our search for scientific articles investigating the effects of the ACV rinse on the carcinogenicity of synthetic hair extensions revealed a notable deficit in the literature regarding scientific studies assessing this practice. While the likelihood that the ACV rinse effectively alters the carcinogenicity of plastic polymers found in synthetic hair extensions and improves their safety seems improbable, the deficit of empirical data evaluating this practice is concerning given both the prevalence of this remedy and the sizable demographic of patients who practice styling with synthetic hair.¹ Of the potential adverse outcomes (eg, contact dermatitis, traction alopecia) that are possible from styling with synthetic hair that have been reported in the literature, carcinogenic exposure from synthetic hair extensions is relatively absent, with the exception of a few publications,^2,3,9 despite its potential to cause serious long-term consequences for hair stylists and those who regularly use these products.

Interestingly, individuals who style their hair with synthetic hair extensions frequently tout the efficacy of the ACV rinse for removal of mostly unidentified irritants, although the effects are unverified.^6,7 While the ACV rinse may be an effective means of removing toxic chemicals from synthetic hair extensions, without verifiable data this method remains an unproven remedy whose perceived benefits could result from factors unrelated to the rinse itself. Theoretically, simply rinsing synthetic hair extensions with plain water prior to use may demonstrate similar efficacy to that of the ACV rinse. 

An additional factor worth mentioning is the lack of government regulations concerning the manufacturing practices of synthetic hair extensions. Flame-retardant materials such as trichloroethylene, polyvinyl chloride, and hexabromocyclododecane frequently are used in synthetic hair extensions despite their known adverse effects, which include reproductive organ toxicity and links to various cancers, leading to them being banned in 5 states.^1,10-12 With no federal ban on these materials, individuals using synthetic hair remain at risk.  

It is unclear what chemicals, irritants, or toxic substances the ACV rinse method could potentially remove from synthetic hair. In general, manufacturers of synthetic hair extensions are not forthcoming with information regarding materials used in the processing of their products despite public inquiries into their manufacturing practices.⁶ Although Whitehurst’s³ curriculum details the process of making synthetic polymer fibers, the overall processes by which these plastics are made to resemble human hair have not been reviewed in academic publications. Should this information be made available to the public, consumers could potentially avoid specific irritants when purchasing synthetic hair extensions.   

The most common management strategy observed in the literature for adverse outcomes attributable to synthetic hair is discontinuation of use²; however, the prevalence and cultural significance of styling with synthetic hair extensions, along with the convenience these styles offer, make this option suboptimal. The scarcity of publications concerning the management of adverse outcomes related to the use of synthetic hair extensions may explain the absence of alternative management recommendations in the literature. Notably, new synthetic hair extensions from manufacturers that exclude plastic polymers and other harmful additives are now available to the public¹³; however, these hair extensions are cost prohibitive and are less accessible compared to synthetic extensions made from modacrylic fibers (eFigures 2 and 3).^1,13-16 

Final Thoughts

The ACV rinse method is an anecdotal remedy for reducing the harm and risk of adverse outcomes and complications associated with synthetic hair extensions. Discontinued use of these components is the only remedy provided within academic literature to address the harmful ingredients found in synthetic hair extensions.² Presently, there are no known data that support or disprove the efficacy of the ACV rinse. Furthermore, no academic guidance specifically supports remedies for mitigating carcinogen exposure risks in patients who style their hair with synthetic extensions. Given the early onset of exposure to synthetic hair in pediatric populations and the substantial demographic utilizing hairstyles that incorporate synthetic hair extensions, concerns regarding potential exposure risks cannot be overstated. Dermatologists should inform their patients of the potential risks associated with styling with synthetic hair extensions, helping them make informed decisions about future styling habits and hair care choices. Lastly, future studies should investigate how, if at all, ACV rinses alter what are arguably the most harmful components of synthetic hair extensions.

Synthetic hair extensions are made from various plastic polymers (eg, modacrylic, vinyl chloride, and acrylonitrile) shaped into thin strands that mimic human hair and are used to add fullness, length, and manageability in individuals with textured hair.^1-3 The plastic polymers used to make synthetic hair, most notably acrylonitrile and vinyl chloride, are known to be toxic to humans.^1-4 The US Environmental Protection Agency classifies acrylonitrile as a probable carcinogen, and vinyl chloride is associated with the development of lymphoma; leukemia; and rare malignancies of the brain, liver, and lungs.^1,4 According to the Occupational Safety and Health Administration, the maximum exposure limits of vinyl chloride and acrylonitrile vapor or gas over an 8-hour period are 1 ppm (0.001 g/L) and 2 ppm (0.002 g/L), respectively.⁵ Exposure levels from wearing synthetic hair extensions easily exceed these maximums; for example, a full head of braids requires application of multiple packets of synthetic hair, resulting in continuous exposure to carcinogenic materials that can last for weeks to months at a time.¹ Furthermore, individuals as young as 3 years old can begin to style their hair with synthetic extensions, which not only leads to potentially harmful carcinogenic exposure in young children but also yields notably high levels of lifetime exposure in individuals who regularly style their hair with these products.

There currently are no regulations barring the use of potentially harmful materials from the manufacturing process for synthetic hair extensions.¹ As a result, rinsing with apple cider vinegar (ACV) is a popular remedy that many users claim can effectively remove harmful chemicals from synthetic hair.^6,7 As this is the only known remedy that aims to address this issue, we conducted a literature review of studies investigating the effects of the ACV rinse on the carcinogenicity of synthetic hair extensions.

Methods

We conducted a search of Google Scholar, JSTOR, Science Direct, the Public Library of Science, and PubMed articles indexed for MEDLINE using the terms ACV, apple cider vinegar rinse, ACV rinse, synthetic hair carcinogens, synthetic fiber carcinogens, synthetic hair extension carcinogens, modacrylic fibers, Kanekalon (a flame-retardant modacrylic fiber), acrylonitrile, and vinyl chloride fibers to identify primary research articles investigating the effects of the ACV rinse on the carcinogenicity of synthetic hair extensions for inclusion in our review. To broaden our search, we did not establish a time frame for publication of the articles included in the study. Articles investigating the ACV rinse that were unrelated to carcinogenicity and synthetic hair extensions were excluded from this study.

Results

Our initial literature search identified 270 articles, which decreased to 180 after removal of duplicates. These 180 articles were screened for relevance based on title and abstract, which yielded 6 articles. None of the 6 articles identified through our literature search discussed synthetic hair and carcinogenicity in the context of the ACV rinse and were subsequently excluded from our review (eFigure 1).

Comment

Potentially harmful chemicals and ingredients in hair care products marketed for textured hair are now established topics in public discourse among those familiar with textured hair care and maintenance^1,8; however, the discourse remains limited. Our search for scientific articles investigating the effects of the ACV rinse on the carcinogenicity of synthetic hair extensions revealed a notable deficit in the literature regarding scientific studies assessing this practice. While the likelihood that the ACV rinse effectively alters the carcinogenicity of plastic polymers found in synthetic hair extensions and improves their safety seems improbable, the deficit of empirical data evaluating this practice is concerning given both the prevalence of this remedy and the sizable demographic of patients who practice styling with synthetic hair.¹ Of the potential adverse outcomes (eg, contact dermatitis, traction alopecia) that are possible from styling with synthetic hair that have been reported in the literature, carcinogenic exposure from synthetic hair extensions is relatively absent, with the exception of a few publications,^2,3,9 despite its potential to cause serious long-term consequences for hair stylists and those who regularly use these products.

Interestingly, individuals who style their hair with synthetic hair extensions frequently tout the efficacy of the ACV rinse for removal of mostly unidentified irritants, although the effects are unverified.^6,7 While the ACV rinse may be an effective means of removing toxic chemicals from synthetic hair extensions, without verifiable data this method remains an unproven remedy whose perceived benefits could result from factors unrelated to the rinse itself. Theoretically, simply rinsing synthetic hair extensions with plain water prior to use may demonstrate similar efficacy to that of the ACV rinse. 

An additional factor worth mentioning is the lack of government regulations concerning the manufacturing practices of synthetic hair extensions. Flame-retardant materials such as trichloroethylene, polyvinyl chloride, and hexabromocyclododecane frequently are used in synthetic hair extensions despite their known adverse effects, which include reproductive organ toxicity and links to various cancers, leading to them being banned in 5 states.^1,10-12 With no federal ban on these materials, individuals using synthetic hair remain at risk.  

It is unclear what chemicals, irritants, or toxic substances the ACV rinse method could potentially remove from synthetic hair. In general, manufacturers of synthetic hair extensions are not forthcoming with information regarding materials used in the processing of their products despite public inquiries into their manufacturing practices.⁶ Although Whitehurst’s³ curriculum details the process of making synthetic polymer fibers, the overall processes by which these plastics are made to resemble human hair have not been reviewed in academic publications. Should this information be made available to the public, consumers could potentially avoid specific irritants when purchasing synthetic hair extensions.   

The most common management strategy observed in the literature for adverse outcomes attributable to synthetic hair is discontinuation of use²; however, the prevalence and cultural significance of styling with synthetic hair extensions, along with the convenience these styles offer, make this option suboptimal. The scarcity of publications concerning the management of adverse outcomes related to the use of synthetic hair extensions may explain the absence of alternative management recommendations in the literature. Notably, new synthetic hair extensions from manufacturers that exclude plastic polymers and other harmful additives are now available to the public¹³; however, these hair extensions are cost prohibitive and are less accessible compared to synthetic extensions made from modacrylic fibers (eFigures 2 and 3).^1,13-16 

Final Thoughts

The ACV rinse method is an anecdotal remedy for reducing the harm and risk of adverse outcomes and complications associated with synthetic hair extensions. Discontinued use of these components is the only remedy provided within academic literature to address the harmful ingredients found in synthetic hair extensions.² Presently, there are no known data that support or disprove the efficacy of the ACV rinse. Furthermore, no academic guidance specifically supports remedies for mitigating carcinogen exposure risks in patients who style their hair with synthetic extensions. Given the early onset of exposure to synthetic hair in pediatric populations and the substantial demographic utilizing hairstyles that incorporate synthetic hair extensions, concerns regarding potential exposure risks cannot be overstated. Dermatologists should inform their patients of the potential risks associated with styling with synthetic hair extensions, helping them make informed decisions about future styling habits and hair care choices. Lastly, future studies should investigate how, if at all, ACV rinses alter what are arguably the most harmful components of synthetic hair extensions.