Long-Term Prognosis of Vaccine-Induced Contact Allergy to Aluminium

TAKE-HOME MESSAGE

• In this study, patients with contact allergy to an aluminium-containing vaccine in the 1990s were patch-tested to aluminium chloride hexahydrate 2%, along with other aluminum preparations, more than 15 years after their first patch test. Similar to findings of the second patch test performed 5 to 10 years after the first patch test, 75% of the patients with prior positive reactions tested negative in the third patch test.
• The findings of this article suggest that further vaccination with aluminium-containing vaccines in patients with prior vaccine granulomas carries a low risk for recurrent contact allergy reactions as children grow older.

–  Ruth McTighe, MD

Written by

 

 

JiaDe Yu MD, MS

Aluminum is one of the most common natural elements found in the earth's crust. It permeates our daily life from soda cans to laptop chassis, deodorant/antiperspirants, and immunotherapy used for allergen desensitization. Most importantly, aluminum is used in many life-saving vaccines to enhance immune response and increase efficacy. Vaccines containing aluminum include Hepatitis A, Hepatitis B, Anthrax, Meningococcal, DTaP, Tdap, human papillomavirus, etc. Aluminum hypersensitivity is estimated to occur in 5.1% of children but only 0.9% of adults. The most common presenting sign of aluminum hypersensitivity after childhood vaccination are subcutaneous granulomas that can either appear locally or distant relative to the site of vaccination. To bring attention to this, the American Contact Dermatitis Society has named Aluminum the 2022 Contact Allergen of the Year.

This prospective cohort study performed by Lidholm et al in Sweden examines the changing prevalence of aluminum allergy. The authors followed a cohort of children enrolled in the Gothenburg Pertussis Vaccine Trials in the 1990s who developed subcutaneous nodules (745 of 76,000). They were patch tested between 1998 and 2002 to aluminum (Cohort 1). Patients from the initial cohort were again patch tested to aluminum 5 years later (Cohort 2). This study focused on patients from the same cohort re-patch tested >15 years later (Cohort 3). 

In Cohort 1, 377 of 495 (76%) children who had a vaccine related granuloma were positive to aluminum. In Cohort 2 (5 years later), only 55 of 241 children initially positive in Cohort 1 (22.8%) had persistent positive reactions to aluminum while 77.2% of those initially positive turned negative. In Cohort 3 (>15 years later), only 5 of 20 (25%) children positive to aluminum in Cohort 2 were still positive. Interestingly, of the 11 children who were initially negative to aluminum in Cohort 2, 2 had positive testing to aluminum in Cohort 3. This seems to confirm that contact allergy to aluminum likely wanes over time possibly due to decreased exposure to aluminum containing vaccines as we age. Limitations to this study include the small sample size of Cohort 3 and lack of delayed reading as some metals may turn positive a week after patch testing.

Extrapolation of these results to other contact allergens is perhaps more interesting and relevant. Patients often wonder if they will "grow out" of allergens. While the jury is still out for more common contact allergens such as fragrances, methylisothiazolinone, formaldehyde, and nickel, for example, there is the possibility that with reduced exposure to contact allergens as regulations change, the prevalence of these allergens will also decrease with age. Prospective cohort studies should be done to determine if this is true.

Abstract

BACKGROUND

A high incidence of local itching subcutaneous nodules and aluminium allergy was observed in clinical trials of a new aluminium adsorbed pertussis vaccine in Gothenburg, Sweden, in the 1990s. A total of 495 children with itching nodules were patch tested with aluminium chloride hexahydrate 2% and an empty Finn Chamber®, 377 (76%) with positive reactions. When 241 of them were re-tested some years later 186 (3 out of 4) had unexpectedly lost their patch test reactivity.

AIM

To investigate the long-term prognosis of vaccine-induced contact allergy to aluminium by a third patch test about 20 years after Patch test I.

METHODS

Twenty individuals with positive and 11 with negative results in Patch test II were tested a third time with the same sensitisers as in in the first two tests. Three additional aluminium preparations were also tested.

RESULTS

A total 15 out of 20 persons with positive results in the second test had lost their patch test reactivity. Two of 11 with negative tests had turned positive again. The addition of the preparations gave no conclusive results.

CONCLUSION

Contact allergy to aluminium caused by vaccination with aluminium-adsorbed vaccines in childhood seems to fade away with time as measured by loss of patch test reactivity.

Contact Dermatitis

Long-term prognosis of vaccine-induced contact allergy to aluminium: Third patch-test with additional test preparations

Contact Derm 2023 Aug 07;[EPub Ahead of Print], AG Lidholm, A Inerot, M Gillstedt, E Bergfors, B Trollfors

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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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Systematic Identification of Copositivity Groups in Standard Series Patch Testing Through Hierarchical Clustering

TAKE-HOME MESSAGE

• This retrospective cross-sectional analysis of patch test results from the 80-allergen Mayo Clinic Standard Series employed hierarchical clustering to identify copositivity groups, or allergens that are frequently positive together. The results not only showed copositivity groups that were well-known from prior research but also demonstrated novel associations, such as between benzalkonium chloride (an antiseptic) and topical antibiotics, specifically neomycin and bacitracin.
• This research adds to our knowledge of allergen relationships and contributes to optimizing the clinical application of patch testing results by guiding contact avoidance recommendations.

–  Ruth McTighe, MD

Written by

 

 

Yul W. Yang MD, PhD

In allergic contact dermatitis, patients are patch-tested to identify potential allergens to avoid. Yet, many patients react simultaneously to multiple related allergens during patch testing. Thus, when counseling patients, it is vital to avoid both patch-positive allergens and related allergens (called co-positivity groups). For example, patients allergic to nickel usually need to avoid cobalt (also found in costume jewellery).

The avoidance of co-positivity groups is a central foundation in patient-directed avoidance algorithms, including the American Contact Dermatitis Society's Contact Allergen Management Program (CAMP) and SkinSAFE. Both databases are designed to educate patients to avoid co-positivity groups based on any positive patch tests. However, both CAMP and SkinSAFE's co-positivity groups have been determined based on clinical experience, suspected chemical similarity, and/or review of small groups of allergen co-positivity rates, rather than systematic review.

In a Mayo Clinic study, we reviewed 10 years of patch tests, encompassing 5943 patients, 394,921 patch tests, distributed among 80 Standard Series allergens. After correcting for background positivity rates, we then systematically identified co-positivity groups in a blinded manner using hierarchical clustering. In addition to identifying 11 established co-positivity groups, we uncovered 4 new allergen associations to consider when counseling patients:

• Glutaraldehyde – sorbitan sesquioleate, resulting from contamination in the patch-test reagent itself. Dermatologists should avoid glutaraldehyde sources that contain sorbitan sesquioleate, as this may confound results.
• Bronopol – MCI/MI
• Benzoic acid – iodopropynyl butylcarbamate
• Benzalkonium chloride – neomycin/bacitracin. Many standard patch-test series only evaluate neomycin/bacitracin, but not benzalkonium chloride. We have found that benzalkonium chloride is the 10th most common allergen at Mayo Clinic,1 and is found ubiquitously, particularly in first-aid products. Patients allergic to neomycin/bacitracin, who have persistent rashes even with avoidance, should consider avoiding benzalkonium chloride also.

We hope that future research uses similar systematic approaches to define co-positivity groups and incorporate these results in patient-directed databases, such as CAMP and SkinSAFE.

Reference

1. Zawawi S, Yang YW, Cantwell HM, et al. Trends in Patch Testing With the Mayo Clinic Standard Series, 2017–2021. Dermatitis. 2023 May 6. doi:10.1089/derm.2023.0063. Online ahead of print. 

Abstract

IMPORTANCE

Patients are frequently copositive for multiple allergens simultaneously, either due to chemical similarity or simultaneous sensitization. A better understanding of copositivity groups would help guide contact avoidance.

OBJECTIVE

To use patient data to systematically determine copositivity groups in the Mayo Clinic Standard Series.

DESIGN, SETTING, AND PARTICIPANTS

In this retrospective cross-sectional analysis, the Mayo Clinic patch test database was queried for pairwise copositivity rates in the 80 allergen Mayo Clinic Standard Series between 2012 and 2021. Data were collected from 3 tertiary care sites of the Mayo Clinic Contact Dermatitis Group and a total of 5943 patients were included, comprising all patients undergoing patch testing to the Mayo Clinic Standard Series allergens.

MAIN OUTCOMES AND MEASURES

Copositivity rates between every 2 allergens in the 80-allergen Mayo Clinic Standard Series were estimated. After background correction, copositivity rates were analyzed using unsupervised hierarchical clustering to systematically identify copositivity groups in an unbiased manner.

RESULTS

Overall, 394 921 total patches were applied to 5943 patients (4164 [70.1%] women, 1776 [29.9%] men, with a mean [SD] age of 52.3 [18.8] years ), comprising 9545 positive reactions. After background correction based on overall positivity rates, hierarchical clustering revealed distinct copositivity groups. Many were supported by prior literature, including formaldehyde releasers, cobalt-nickel-potassium dichromate, acrylates, 3-dimethylaminopropylamine-amidoamine-oleamidopropyl dimethylamine, alkyl glucosides, budesonide-hydrocortisone-17-butyrate, certain fragrances, compositae-sesquiterpene lactone mix, mercapto mix-mercaptobenzothiazole, carba mix-thiuram mix, and disperse orange-p-phenylenediamine. However, novel associations were also found, including glutaraldehyde-sorbitan sesquioleate, benzalkonium chloride-neomycin-bacitracin, bronopol-methylchloroisothiazolinone-methylisothiazolinone, and benzoic acid-iodopropynyl butylcarbamate.

CONCLUSIONS AND RELEVANCE

This retrospective cross-sectional analysis found that copositivity rates varied between allergens; allergens with extremely high positivity rates demonstrated nonspecific copositivity to multiple other allergens. Background correction based on positivity rates followed by hierarchical clustering confirmed prior known copositivity groups, contaminants and/or excipients leading to copositivity, and novel associations to guide contact avoidance.

JAMA Dermatology

Systematic Identification of Copositivity Groups in Standard Series Patch Testing Through Hierarchical Clustering

JAMA Dermatol 2023 Aug 02;[EPub Ahead of Print], YW Yang, JA Yiannias, MM Voss, MR Hall, MJ Youssef, MDP Davis, DH Voelker, MC Klanderman, AR Mangold 

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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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MetS and Psoriasis

Metabolic Syndrome, Hypertension, And Waist Circumference Appear To Be Risk Factors In Psoriasis Development, Research Suggests

HCPlive (8/22, Smith) reports, "Metabolic syndrome (MetS), hypertension, and waist circumference...are risk factors in psoriasis development...indicating possible effectiveness of early management of MetS in diminishing the risk of psoriasis," according to a study that "included 231,430 controls, 59,677 MetS cases, 463,010 hypertension subjects, 462,166 waist circumference samples, 441,016" triglyceride "samples, and 441,016" high-density lipoprotein cholesterol samples. The findings were published online in the Journal of 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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Sociodemographic and Clinical Characteristics Associated With Multiple Biologic Failure in Patients With Psoriasis

TAKE-HOME MESSAGE

• This prospective cohort study of 1039 patients with psoriasis found that female sex, prior non-biologic systemic therapy use, shorter disease duration, earlier biologic initiation, hyperlipidemia, and Medicaid insurance were the factors associated with multiple biologic failure (MBF). Health-related behaviors and the extent of psoriasis were not significant predictors of MBF. Switching from a TNF-α inhibitor to an IL-17 inhibitor, an IL-12/23 inhibitor to an IL-17 inhibitor, and a TNF-α inhibitor to an IL-12/23 inhibitor were the most common first-to-second biologic sequences associated with MBF.
• This study highlights specific factors associated with poor therapeutic response to multiple biologic agents in patients with psoriasis, which may help to risk-stratify patients at a higher risk of biologic switching or treatment failure.

–  Lillian Sun, MD

BACKGROUND

Psoriasis patients with poor therapeutic response to multiple biologic agents are not well-characterized.

OBJECTIVE

To describe the characteristics associated with development of multiple biologic failure (MBF) versus good clinical response (GR) to the first biologic.

METHODS

This prospective cohort analysis evaluated patients in the multi-center CorEvitas Psoriasis Registry who initiated their first biologic between 2015-2020 and were followed for ≥24 months. Multivariable logistic regression identified sociodemographic, clinical, and patient-reported outcomes that differed between MBF (discontinued ≥2 biologics of different classes, each used for ≥90 days, due to inadequate efficacy) and GR (continued use of first biologic for ≥2 years) patients.

RESULTS

1,039 patients were analyzed (490 GR (47.2%), 65 MBF (6.3%)). Female sex, shorter psoriasis duration, earlier year of biologic initiation, prior non-biologic systemic therapy use, history of hyperlipidemia, and Medicaid insurance were significantly associated with MBF, though the latter two variables exhibited wider confidence intervals, indicating a lower level of support. The first-to-second biologic sequence most observed with MBF was TNF-α inhibitor to IL-17 inhibitor use.

LIMITATIONS

Biologic adherence between visits was not evaluated.

CONCLUSION

Approximately 6% of psoriasis patients met MBF criteria. The results identify characteristics associated with MBF that may distinguish patients warranting more frequent follow-up.

Journal of the American Academy of Dermatology

Sociodemographic and clinical characteristics associated with multiple biologic failure in psoriasis: a 2015-2022 prospective cohort analysis of the CorEvitas Psoriasis Registry

J Am Acad Dermatol 2023 Jul 24;[EPub Ahead of Print], JQ Jin, A Cronin, C Roberts-Toler, S Yeroushalmi, E Hadeler, RK Spencer, KG Elhage, G Gondo, EB Wallace, SM Reddy, G Han, J Kaffenberger, MS Davis, M Hakimi, JU Scher, AW Armstrong, T Bhutani, RR McLean, W Liao

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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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