PTDS allergen of the year

THE 2025 ALLERGEN OF THE YEAR IS TO DYE FOR

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By Christen Mowad, MD, FAAD
Oct. 29, 2025
Vol. 7, No. 43

The "Allergen of the Year" announcement is always much anticipated in the world of contact dermatitis and patch testing. This year the honor has gone to toluene-2,5-diamine sulfate (PTDS). (1) PTDS is an aromatic amide that is used as a hair dye, textile dye, and in color photography. It was named allergen of the year of 2025 to not only highlight its potential as an allergen but also its potential as an alternative hair dye chemical for those who are allergic to paraphenylenediamine (PPD). PTDS is used in many permanent hair dyes and is also known as 2,5-diaminotoluene sulfate, p-toluenediamine sulfate, toluene-2,5-diamine hemisulfate, 2,5-toluenediamine sulfate, and paratoluenediamine sulfate. As with so many other allergens, this chemical is not included in the FDA-approved standard screening series. It is also not in many standard expanded screening series and therefore can be missed as a cause of allergy — another reason for highlighting this allergen. 

For those that are allergic to PPD, testing to PTDS is useful as it can function as an alternative to PPD if the patient is negative upon testing to PTDS. Relevance for those allergic to PTDS is over 70% in many studies and this is especially true for hairdressers given its narrow range of use. Clinically, PTDS ACD presents as an eczematous reaction in places where hair dye comes in contact with the skin — most commonly the hands, hairline, and periorbital areas. This reaction is typically associated with pruritus and can have vesiculobullous findings depending on the severity of the reaction. 

The image demonstrates an allergic contact dermatitis that developed within 48 hours after applying black hair dye containing paraphenylenediamine. JAAD Case Reports 2024; 43: 7-8.

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Occupational contact dermatitis (OCD) to this chemical is most often seen with hairdressers who are 1.7-2.5 times greater than the general population to have hand dermatitis. Cross reactions between PTDS and PPD can occur. PTDS allergic patients are often PPD allergic. Several studies have demonstrated that 80-100% of patients with PTDS allergy are also allergic to PPD. The reverse does not hold as studies show that 30-50% of PPD allergic patients are also allergic to PTDS, indicating that PTDS may be an alternative hair dye for those allergic to PPD. However, patch testing should be performed first to confirm if PTDS is tolerated. 

The allergen of the year is a tool for those firmly entrenched in the patch testing world to highlight allergens of particular significance. PTDS has been given the honor this year to showcase its potential as an alternative hair dye chemical to those who are PPD allergic and to highlight its potential as an allergen as well that must be considered given it is not routinely tested in standard and even expanded series. 

Point to Remember: Toluene-2,5-diamine sulfate (PTDS) may be an allergen but may also be used as a substitute in some patients allergic to the hair dye paraphenylene diamine. 

Our expert's viewpoint

Bruce A. Brod, MD, MHCI, FAAD
Associate Dean of Continuing Medical Education
Clinical Professor of Dermatology
University of Pennsylvania Perelman School of Medicine

Color me Cautious

The 2025 Allergen of the Year, toluene-2,5-diamine sulfate (PTDS), is a fitting choice not just for its allergenic potential, but for its dual identity as a PPD alternative and a frequent co-sensitizer. (1) Structurally similar to para-phenylenediamine (PPD), PTDS is often found in oxidative hair dyes alongside other aromatic amines. In my patch test clinic when testing suspect dye allergy patients, I routinely include m-aminophenol, p-aminophenol, and other aromatic dyes, as well as both PPD and PTDS for patients with scalp, neck, or facial dermatitis linked to hair dye use. 

The FDA requires warning labels on consumer products for coal-tar-based dyes like PPD and PTDS, advising consumers to always perform a patch test 48 hours before each use of hair dye even if they've used the product before as reactions can develop over time. (2)

In addition to PPD and PTDS, hair dyes often contain other potential allergens, including fragrance components and preservatives like methylisothiazolinone, which can contribute to allergic contact dermatitis and should not be overlooked in patch testing.

The good news is that the market for natural hair dyes is expanding. Products based on pure henna (Lawsonia inermis), indigo, cassia, and herbal blends are increasingly available and often marketed as safer alternatives. These dyes are generally free of oxidative agents and aromatic amines, making them less likely to cause allergic contact dermatitis.

However, natural doesn't always mean safe. A growing concern is the adulteration of hair dyes, especially in small ethnic markets. A recent study analyzed 51 hair dye products marketed as "PPD-free" and found that nearly 10% contained undeclared PPD, with some at concentrations high enough to trigger allergic reactions in sensitized individuals even though the ingredient was not listed on the label. (3)

The bottom line is most oxidative dyes are complex chemical mixtures. PTDS may be a substitute for some, but it's no panacea. Comprehensive patch testing, patient education, and awareness of both synthetic and natural allergen risks are essential. As we continue to explore safer alternatives, we must also advocate for clearer labeling, regulatory oversight, and expanded allergen screening to better protect our patients.

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References

1. Atwater AR, Botto N. Toluene-2,5-Diamine Sulfate: Allergen of the Year 2025. Dermatitis. 2025;36(1):3-11. doi:10.1089/derm.2024.0384. 

2. U.S. Food and Drug Administration. Hair Dye and Hair Dye Safety. Updated 2023. Available at: https://www.fda.gov. 

3. Needle CD, Milam EC, Korman A, et al. Contact Allergens in "PPD-Free" Hair Dyes. Dermatitis. 2025;00(0):1–7. doi:10.1089/derm.2024.05423. 

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Topicos en DA

Daily Emollient Use In Early Infancy Tied To Lower Atopic Dermatitis Incidence At 2 Years Of Age, Study Finds

Dermatology Advisor (8/27, Saha) reported a study found that "daily full-body application of emollients starting in early infancy reduced the incidence of atopic dermatitis (AD) at 2 years of age in a diverse United States population." Researchers observed that "at 2 years, the cumulative incidence of AD was significantly lower in the intervention group (36.1%) compared with the control group (43.0%), yielding a relative risk (RR) of 0.84. The protective effect of daily emollient use was especially notable among infants without a family history of atopic disease. The presence of a dog in the household enhanced the protective effect, while no added benefit was observed in households without pets." The study was published in JAMA Dermatology.

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Benjamin Hidalgo-Matlock
Skin Care Physicians of Costa Rica

Clinica Victoria en San Pedro: 4000-1054
Momentum Escazu: 2101-9574

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VEXAS ( vacuoles E1 enzyme X-linked autoinflammatory somatic syndrome )

dermatologyadvisor.com

ACR Releases International Consensus Guidance on Managing VEXAS Syndrome

5–7 minutes

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The American College of Rheumatology (ACR) recently issued the first formal international consensus guidance statement on diagnosing and managing vacuoles E1 enzyme X-linked autoinflammatory somatic syndrome (VEXAS), which appeared in Arthritis & Rheumatology.

A multidisciplinary panel of 57 experts from 18 countries — representing rheumatology, hematology, dermatology, genetics, immunology, internal medicine, infectious disease, pathology, and critical care — developed the consensus guidance. The process included structured virtual meetings, subgroup literature reviews of PubMed and Medline for articles published from January 2020 to August 2024, and a 2-day international workshop in Paris in May 2024.

Draft statements were refined through iterative discussions and finalized through electronic voting, with at least 80% agreement required. Evidence quality was assessed using the Grading of Recommendations Assessment, Development and Evaluation methodology, but most recommendations remain conditional due to limited prospective data and a lack of randomized controlled trials.

Clinical Features

Vacuoles E1 enzyme X-linked autoinflammatory somatic syndrome is a hematoinflammatory disease caused by somatic mutations in the UBA1 gene. It primarily affects men aged at least 50 years, though rare cases have been reported among women with monosomy X and younger patients.

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VEXAS is a newly recognized disease, and these clinical guidance statements are intended to help clinicians better manage this condition.

Clinical features are heterogeneous, with persistent systemic inflammation and overlapping rheumatologic, dermatologic, and hematologic manifestations. Common findings include recurrent fevers (75%-100%), skin involvement such as erythema nodosum, panniculitis, and urticarial lesions (85%), lung disease with interstitial infiltrates or pleuropericarditis (55%-95%), auricular and nasal chondritis (14%-64%), ocular inflammation (20%-50%), and venous thrombosis (~50%). The guideline authors emphasized the importance of clinicians and other health care providers being familiar with these common features.

Hematologic abnormalities are frequent, with macrocytic anemia the most common, though lymphopenia, thrombocytopenia, and monocytopenia often emerge as the disease progresses. Vacuoles in bone marrow precursor cells are suggestive but not diagnostic, and UBA1 genetic testing is required for confirmation; VEXAS is not heritable, as all reported cases arise from acquired mutations. Persistent elevation of inflammatory markers accompanied by skin, ocular, lung, or cartilage involvement and/or cytopenia should raise suspicion for VEXAS.

Genetic Testing and Diagnosis

Most patients have missense or splice site mutations in exon 3 of UBA1. Sequencing methods vary based on resources, with next-generation sequencing offering the highest sensitivity for low-level variants, while targeted Sanger sequencing of exon 3 provides a cost-effective initial approach.

Bone marrow testing should be considered when peripheral blood testing is negative despite high clinical suspicion. Because cytopenias are common, bone marrow examination is recommended among patients with confirmed VEXAS to exclude associated hematologic neoplasms, particularly myelodysplastic syndrome (MDS). Interpretation can be challenging due to frequent dysplasia in VEXAS, which can mimic MDS, and therefore, cytogenetics and molecular testing are advised.

Mutational profiles often include DNMT3A and TET2, reflecting overlap with clonal hematopoiesis. Most MDS cases in VEXAS are lower risk, with limited progression to acute myeloid leukemia.

Management and Outcomes

Management of VEXAS requires a multidisciplinary team, ideally with referral to expert centers. Treatment goals include controlling inflammation, preventing bone marrow failure, minimizing treatment-related complications, and improving quality of life.

Glucocorticoids remain the cornerstone of therapy, often requiring moderate to high daily doses, but tapering should be attempted to reduce long-term toxicity. Steroid-sparing therapies targeting innate immune pathways — such as Janus kinase inhibitors and interleukin-6 inhibitors — have shown greater benefit than conventional disease-modifying anti-rheumatic drugs or B cell-directed therapies. Azacitidine may reduce clonal burden in some patients, while allogeneic stem cell transplantation offers a potential cure but is limited to carefully selected patients with severe or refractory disease due to high procedural risks.

Supportive measures are essential, including prophylaxis against opportunistic infections, thromboprophylaxis for patients at risk for thromboembolic disease, and active management of glucocorticoid-related complications such as bone loss and cardiovascular risks. Despite these approaches, the median survival from symptom onset is approximately 10 years.

Conclusion

This consensus guidance highlights the need for early recognition of VEXAS, genetic confirmation of UBA1 mutations, and integrated management addressing both inflammatory and hematologic disease.

The guideline authors concluded, "VEXAS is a newly recognized disease, and these clinical guidance statements are intended to help clinicians better manage this condition."

This article originally appeared on Rheumatology Advisor

AGA nutri

Adding Dietary Supplement Improves Pharmacologic Treatment Efficacy In Patients With AGA, Study Finds

Dermatology Advisor (10/10, Goldberg) reported a study found that "clinical efficacy of minoxidil and finasteride among men and women with mild to severe androgenic alopecia (AGA) is enhanced with the use of an oral, novel dietary supplement, AGA-P," that contains "zinc, vitamin C, L-Cystine 425 mg, Cururbita pepo extract 320 mg, and Serenoa repens extract 320 mg." For the study, "participants were randomly assigned 1:1 to receive pharmacological treatment (primarily topical minoxidil and oral finasteride) plus 1 daily capsule of the dietary supplementation or pharmacological treatment alone." The researchers observed that "compared with drug treatment alone, the clinical efficacy of pharmacological treatments for mild to severe AGA was increased significantly with oral supplementation. Improvement on a 7-point Global Assessment Scale (GAS) was 36.5% for group A vs 25.0% for group B. Subjective participant feedback showed 46% of group A and 30% of group B reported great improvement." The study was published in the Journal of Cosmetic Dermatology.