A patch test, in which a test substance is applied under a patch on the skin, has produced an allergic reaction to a fragrance ingredient. Does that mean dermatitis will also occur at a lower concentration, closer to that in everyday products? Being able to react in a diagnostic test and actually developing symptoms under a particular pattern of product use are related, but they are not the same question.
A study reported by Thanisorn Sukakul and colleagues in 2024 examined this relationship for linalool hydroperoxides, which form when linalool oxidizes. Linalool is used as a fragrance ingredient, but this study measured skin reactions to its oxidation products, not the effects of unoxidized linalool in general.
Comparing patch testing with repeated application
The researchers enrolled 48 people at a dermatology department in Sweden. Forty-seven completed the study after one person was unable to attend the first reading. They compared 31 people who had tested positive for linalool hydroperoxides in an earlier or current patch test with 16 negative controls. The controls were also patients who had received care for dermatitis, not a group recruited from the healthy general population.
The study used three creams containing these oxidation products at 44, 140, and 440 ppm, plus a control cream without them. Parts per million, or ppm, is a concentration unit: 440 ppm corresponds to 0.044%. The authors selected these concentrations with reference to ranges reported in product analyses and case reports. They do not represent the concentrations in every commercial product.
Participants applied each cream to a designated area of the forearms without visible rash twice daily for 28 days. Unlike an occluded patch test, this repeated open application test, or ROAT, leaves the application sites uncovered. The creams were coded, and neither participants nor assessors knew their contents. A dermatologist assessed reactions every few days.
Patch tests using several concentrations were also performed on the back. The patches remained in place for 48 hours before subsequent readings. Because the concentration, cream or petrolatum vehicle, occlusion, site, and exposure time differed, the two tests cannot simply be treated as equivalent exposures.
One positive reaction on day 28
During repeated application, one of the 31 people in the contact-allergy group developed a positive reaction to the highest concentration, 440 ppm, on day 28. None of the 16 controls tested positive. However, the sample was small, and the difference in positive reaction rates between groups was not statistically significant.
On day 21, two people had small raised bumps and redness at the highest-concentration site, but neither reaction yet met the study’s criteria for a positive result. One of these reactions progressed and was positive on day 28. A result not classified as positive should be distinguished from an absence of any skin changes.
The authors concluded that positive reactions were rare when these cream concentrations were used for four weeks on skin without obvious rash. Having acquired the capacity to mount an allergic response to a substance is called sensitization. One participant did react in this study, so the results do not mean that everyone who is sensitized can use such products.
A negative retest does not establish that an allergy has disappeared
Repeat patch testing also produced an important finding. Thirteen people who had previously tested positive did not do so this time. They remained in the contact-allergy group because of their history. Conversely, one person who had previously tested negative now tested positive and changed groups.
Among 20 people whose previous reaction had been weakly positive, 12 were negative on retesting. Among ten with a previous strong or extremely positive reaction, one was negative. This difference was statistically significant: weaker reactions were less reproducible.
The authors nevertheless caution that a negative retest alone should not be taken to establish the absence of contact allergy. Skin reactivity and previous exposure, among other factors, may change. The data also show why a single positive or negative result is difficult to treat as a fixed characteristic.
Skin condition matters, not just concentration
The paper notes that earlier repeated-application research used higher concentrations and larger application amounts. Rather than interpreting the small number of reactions here as evidence that earlier studies were wrong, the authors argue that differences in the dose reaching the skin must be considered. Positive reaction rates cannot be compared directly across studies with different vehicles, participants, or application periods, either.
The participant with a positive reaction also had a history of dermatitis on the hands and wrists. The authors suggest that even the apparently unaffected forearms might have had subtle inflammation or impaired barrier function. This could have increased penetration and contributed to the reaction, but it was not a mechanism established by direct measurement.
The trial did not test application to damaged skin. The authors also identify the absence of an objective method for measuring adherence to the application instructions as a limitation. The findings cannot determine what would happen with other product types, longer-term use, or symptoms caused by inhalation.
Summary
Even among people with a history of positive patch tests for linalool hydroperoxides, most did not develop a positive reaction under this study’s conditions: repeated application of low-concentration creams to forearms without obvious rash. The authors revisited the real-life significance of diagnosis: under what everyday exposure conditions does the reactivity detected by a patch test lead to dermatitis?
Answering that question requires connecting not only the strength of the test reaction but also the amount of oxidation products in a product, its vehicle, the amount applied, and the condition of the skin. This study does not invalidate patch tests or establish the safety of fragranced products as a whole. If an allergy has already been identified, decisions about product use or retesting should be discussed in clinical care rather than made on the basis of this result alone.
The research received funding from HudFonden, which supports dermatological research in Sweden. Bruze disclosed membership of the Expert Panel for Fragrance Safety, and Svedman disclosed participation in the IDEA project supported by the International Fragrance Association (IFRA).
References
Sukakul, T., Bruze, M., Mowitz, M., Kiuru, A., & Svedman, C. (2024). Allergic Contact Dermatitis to Linalool Hydroperoxides: Pitfalls in the Diagnostic Process—Findings from a Repeated Open Application Test Study. Dermatitis, 35(4), 373–379. DOI: 10.1089/derm.2023.0286 / Full article. © 2024 American Contact Dermatitis Society. All Rights Reserved.
