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Aluminum: The 2022 American Contact Dermatitis Society Allergen of the Year
Author(s)
Danielle E. Novack, BA
Jiade Yu, MD
Brandon L. Adler, MD

No time of the year is more exciting than the unveiling of the American Contact Dermatitis Society Allergen of the Year. Sometimes the selected allergen represents a completely novel cause of allergic contact dermatitis (ACD) with an unpronounceable chemical name. Not this time! The 2022 Allergen of the Year is likely to be lurking in your kitchen drawer at this very moment, as this year aluminum was chosen for this most prestigious honor.1 But do not throw out your aluminum foil just yet—aluminum allergy tends to be confined to specific scenarios. In this article, we highlight the growing recognition of aluminum contact allergy, particularly in the pediatric population, focusing on distinct presentations of aluminum ACD, unique sources of exposure, and nuances of patch testing to this metal.

Aluminum Is All Around Us

As the third most common element in the Earth’s crust, aluminum can be found quite literally everywhere.1 However, aluminum rarely is found in its pure elemental form; instead, it reacts with other elements around it, most commonly oxygen, to form aluminum-containing compounds. Known for their stability and safety, aluminum and its salts are incorporated in myriad products ranging from electronic equipment to foods and their packaging, medications, cosmetics, orthopedic and dental implants, and even tattoos. Aluminum also is found in the air and water supply and may even be encountered in certain workplaces, such as aircraft and machine industries. As such, contact with aluminum is all but certain in modern life.

The use of aluminum in consumer products is widely accepted as safe by public health agencies in the United States.2 Although there has been public concern that aluminum could be linked to development of breast cancer or Alzheimer disease, there is no clear evidence that these conditions are associated with routine aluminum exposure through ingestion or consumer products.3-5

Aluminum Contact Allergy

In part because of its ubiquity and in part because of the stability of aluminum-containing compounds, it was long thought that aluminum was nonallergenic. Contact allergy to elemental aluminum is rare; on the other hand, aluminum salts (the forms we are likely to encounter in daily life) are now recognized in the field of contact dermatitis as allergens of significance, particularly in the pediatric population.1,6

First reported as a possible occupational allergen in 1944,7 aluminum allergy came to prominence in the 1990s in association with vaccines. Aluminum is included in some vaccines as an adjuvant that bolsters the immune response8; the eTable lists currently available aluminum-containing vaccines in the United States; of note, none of the COVID-19 vaccines approved in the United States or Europe contain aluminum.11 Although the use of aluminum in vaccines is considered to be safe by the US Food and Drug Administration and Centers for Disease Control and Prevention,12,13 a small number of children become sensitized to aluminum through vaccines and may develop persistent pruritic subcutaneous nodules (also known as vaccination granulomas) at the injection site; however, the incidence of this adverse effect was less than 1% in large studies including as many as 76,000 children, suggesting that it is relatively rare.14,15 Upon patch testing, aluminum allergy has been detected in 77% to 95% of such cases.14 There is wide variation in the onset of the nodules ranging from weeks to years following vaccination.15 Due to pruritus, the examination may reveal accompanying excoriations, hyperpigmentation, and sometimes hypertrichosis at the injection site. Aluminum allergy related to vaccination also can manifest with widespread eruptions representing systemic contact dermatitis.16

Vaccines Containing Aluminum Adjuvants Currently Available in the United States

Along with vaccines, the second major source of aluminum sensitization is allergen-specific immunotherapies administered by allergists/immunologists, many of which contain aluminum hydroxide.17,18

On the consumer product front, antiperspirants are the most common source of cutaneous exposure to aluminum. Aluminum complexes react with electrolytes in sweat to form plugs in eccrine ducts, thereby preventing sweat excretion.6 Allergic contact dermatitis to these products presents with axillary-vault dermatitis. There also have been reports of ACD to aluminum in sunscreen and toothpaste, with the latter implicated in causing systemic ACD.19,20

 

 

Prevalence of Sensitization to Aluminum

There have been a few large-scale studies evaluating rates of sensitization to aluminum in general patch-test patient populations; additionally, because of the complexities of testing this metal, investigators have utilized differing formulations for patch testing. A recent Swedish study found that 0.9% of 5448 adults and 5.1% of 196 children showed positive reactions to aluminum chloride hexahydrate (ACH) 10% in petrolatum and/or aluminum lactate 12% in petrolatum.21 Notably, there was a significant association between aluminum allergy and history of atopy for both adults (P=.0056) and children (P=.046), which remains to be further explored. A systematic review and meta-analysis found comparable rates of aluminum allergy in 0.4% of adults and 5.6% of children without vaccine granulomas who were tested.22 With this evidence in mind, it has been recommended by contact dermatitis experts that aluminum be included in pediatric baseline patch test series and also investigated for potential inclusion in baseline series for adults.1

Differential Diagnosis of Aluminum ACD

The differential diagnosis for subcutaneous nodules following vaccination is broad and includes various forms of panniculitis, sarcoidosis, foreign body reactions, vascular malformations, infections, and malignancies.23-25 The diagnosis may be obscured in cases with delayed onset. Biopsy is not mandatory to establish the diagnosis; although variable histopathologic findings have been reported, a common feature is histiocytes with abundant granular cytoplasm.26 It may be possible to demonstrate the presence of aluminum particles in tissue using electron microscopy and X-ray microanalysis.

For those patients who present with axillary-vault dermatitis, the differential includes ACD to more common allergens in antiperspirants (eg, fragrance), as well as other axillary dermatoses including inverse psoriasis, erythrasma, Hailey-Hailey disease, and various forms of intertrigo. Dermatitis localized to the axillary rim suggests textile allergy.

Patch Testing to Aluminum

Due to its physicochemical properties, patch testing for aluminum allergy is complicated, and historically there has been a lack of consensus on the ideal test formulation.1,27,28 At this time, it appears that the most sensitive formulation for patch testing to aluminum is ACH 10% in petrolatum.1 Some contact dermatitis experts recommend that children younger than 8 years should be tested with ACH 2% in petrolatum to minimize the risk of extreme patch test reactions.29,30 In some patients sensitized to aluminum, the use of aluminum patch test chambers has been noted to produce false-positive reactions, taking the form of multiple ring-shaped reactions to the chambers themselves or reactions to certain allergens whose chemical properties cause corrosion of the aluminum within the chambers.31-33 Therefore, when testing for suspected aluminum allergy, plastic chambers should be used; given the higher prevalence of aluminum allergy in children, some clinics routinely use plastic chambers for all pediatric patch testing.34 Importantly, elemental aluminum, including empty aluminum test chambers or aluminum foil, alone is not sufficient for patch testing as it lacks sensitivity.1 Additionally, nearly 20% of positive tests will be missed if a day 7 reading is not performed, making delayed reading a must in cases with high suspicion for aluminum allergy.21

Management of Aluminum Allergy

The development of pruritic subcutaneous nodules is uncomfortable for children and their guardians alike and may be associated with prolonged symptoms that negatively impact quality of life35,36; nonetheless, expert authorities have determined that the preventive benefits of childhood vaccination far outweigh any risk posed by the presence of aluminum in vaccines.12,13,37 Because aluminum-free formulations may not be available for all vaccines, it is essential to educate patients and families who may be at risk for developing vaccine hesitancy or avoidance.35,36,38 Given the hypothesis that epidermal dendritic cells mediate aluminum sensitization, it has been proposed that vaccine administration via deep intramuscular rather than subcutaneous injection may mitigate the risk, but more evidence is needed to support this approach.39,40 The good news is that the nodules tend to fade with age, with a median time to resolution of 18 to 49 months.14 In addition, patients may experience loss of sensitization to aluminum over time41; in one study, 77% of 241 children lost patch test reactivity when retested 5 to 9 years later.42 The exact reason for this diminishment of reactivity is not well understood. Adjunctive treatments to relieve symptoms of vaccine granulomas include topical and intralesional corticosteroids and antihistamines.

For patients reacting to aluminum in antiperspirants, there are many aluminum-free formulations on the market as well as recipes for homemade antiperspirants.6 On a case-by-case basis, patients may need to avoid aluminum-containing medications, permanent tattoos, and orthopedic or dental implants. To the best of our knowledge, there is no evidence suggesting a need to avoid aluminum in foods and their containers in routine daily life; although some patients report exacerbations of their symptoms associated with food-related aluminum exposures (eg, canned food, dried fruit) and improvement with dietary modification, further investigation is needed to confirm the relevance of these sources of contact.36,38 For patients who require allergen-specific immunotherapy, aluminum-free allergen extracts are available.6

Final Interpretation

Exposure to aluminum is ubiquitous; although relatively uncommon, awareness of the potential for ACD to aluminum is increasingly important, particularly in children. Given the prevalence of aluminum contact allergy, it has been recommended by contact dermatitis experts for inclusion in baseline pediatric patch test series.1 Although it is a complex issue, the development of ACD in a small proportion of children exposed to aluminum in vaccines does not outweigh the benefit of vaccination for almost all children. When conducting patch testing to aluminum, studies support testing to ACH 10% in petrolatum for adults, and consider reducing the concentration to ACH 2% for children.

Acknowledgment—The authors thank Ian Fritz, MD (South Portland, Maine), for his critical input during preparation of this article.

References
  1. Bruze M, Netterlid E, Siemund I. Aluminum—Allergen of the Year 2022. Dermatitis. 2022;33:10-15.
  2. Toxicological profile for aluminum. Agency for Toxic Substances and Disease Registry website. Accessed June 22, 2022. https://wwwn.cdc.gov/TSP/ToxProfiles/ToxProfiles.aspx?id=191&tid=34
  3. Klotz K, Weistenhöfer W, Neff F, et al. The health effects of aluminum exposure. Dtsch Arztebl Int. 2017;114:653-659.
  4. Liszewski W, Zaidi AJ, Fournier E, et al. Review of aluminum, paraben, and sulfate product disclaimers on personal care products [published online June 16, 2021]. J Am Acad Dermatol. doi:10.1016/j. jaad.2021.06.840
  5. Van Dyke N, Yenugadhati N, Birkett NJ, et al. Association between aluminum in drinking water and incident Alzheimer’s disease in the Canadian Study of Health and Aging cohort. Neurotoxicology. 2021;83:157-165.
  6. Kullberg SA, Ward JM, Liou YL, et al. Cutaneous reactions to aluminum. Dermatitis. 2020;31:335-349.
  7. Hall AF. Occupational contact dermatitis among aircraft workers. J Am Med Assoc. 1944;125:179-185.
  8. HogenEsch H. Mechanism of immunopotentiation and safety of aluminum adjuvants. Front Immunol. 2012;3:406.
  9. Vaccine exipient summary. Centers for Disease Control and Prevention website. Published November 2021. Accessed June 22, 2022. https://www.cdc.gov/vaccines/pubs/pinkbook/downloads/appendices/b/excipient-table-2.pdf
  10. Vaccines licensed for use in the United States. US Food and Drug Administration website. Updated January 31, 2022. Accessed June 22, 2022. https://www.fda.gov/vaccines-blood-biologics/vaccines/vaccines-licensed-use-united-states
  11. Swenson A. US and EU COVID vaccines don’t contain aluminum. AP News. Published March 16, 2021. Accessed June 22, 2022. https://apnews.com/article/fact-checking-afs:Content:9991020426
  12. Adjuvants and vaccines. Centers for Disease Control and Prevention website. Updated August 4, 2020. Accessed June 22, 2022. https://www.cdc.gov/vaccinesafety/concerns/adjuvants.html
  13. Common ingredients in U.S. licensed vaccines. US Food and Drug Administration website. Updated April 19, 2019. Accessed June 22, 2002. https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/common-ingredients-us-licensed-vaccines
  14. Bergfors E, Hermansson G, Nyström Kronander U, et al. How common are long-lasting, intensely itching vaccination granulomas and contact allergy to aluminium induced by currently used pediatric vaccines? a prospective cohort study. Eur J Pediatr. 2014;173:1297-1307.
  15. Bergfors E, Trollfors B, Inerot A. Unexpectedly high incidence of persistent itching nodules and delayed hypersensitivity to aluminium in children after the use of adsorbed vaccines from a single manufacturer. Vaccine. 2003;22:64-69.
  16. Mistry BD, DeKoven JG. Widespread cutaneous eruption after aluminum-containing vaccination: a case report and review of current literature. Pediatr Dermatol. 2021;38:872-874.
  17. Netterlid E, Hindsén M, Björk J, et al. There is an association between contact allergy to aluminium and persistent subcutaneous nodules in children undergoing hyposensitization therapy. Contact Dermatitis. 2009;60:41-49.
  18. Netterlid E, Hindsén M, Siemund I, et al. Does allergen-specific immunotherapy induce contact allergy to aluminium? Acta Derm Venereol. 2013;93:50-56.
  19. Hoffmann SS, Elberling J, Thyssen JP, et al. Does aluminium in sunscreens cause dermatitis in children with aluminium contact allergy: a repeated open application test study. Contact Dermatitis. 2022;86:9-14.
  20. Veien NK, Hattel T, Laurberg G. Systemically aggravated contact dermatitis caused by aluminium in toothpaste. Contact Dermatitis. 1993;28:199-200.
  21. Siemund I, Dahlin J, Hindsén M, et al. Contact allergy to two aluminum salts in consecutively patch-tested dermatitis patients. Dermatitis. 2022;33:31-35.
  22. Hoffmann SS, Wennervaldt M, Alinaghi F, et al. Aluminium contact allergy without vaccination granulomas: a systematic review and metaanalysis. Contact Dermatitis. 2021;85:129-135.
  23. Bergfors E, Lundmark K, Kronander UN. Case report: a child with a long-standing, intensely itching subcutaneous nodule on a thigh: an uncommon (?) reaction to commonly used vaccines [published online January 13, 2013]. BMJ Case Rep. doi:10.1136/bcr-2012-007779
  24. Mooser G, Gall H, Weber L, et al. Cold panniculitis—an unusual differential diagnosis from aluminium allergy in a patient hyposensitized with aluminium-precipitated antigen extract. Contact Dermatitis. 2001;44:366-375.
  25. Mulholland D, Joyce EA, Foran A, et al. The evaluation of palpable thigh nodularity in vaccination-age children—differentiating vaccination granulomas from other causes. J Med Ultrasound. 2021;29:129.
  26. Chong H, Brady K, Metze D, et al. Persistent nodules at injection sites (aluminium granuloma)—clinicopathological study of 14 cases with a diverse range of histological reaction patterns. Histopathology. 2006;48:182-188.
  27. Nikpour S, Hedberg YS. Using chemical speciation modelling to discuss variations in patch test reactions to different aluminium and chromium salts. Contact Dermatitis. 2021;85:415-420.
  28. Siemund I, Zimerson E, Hindsén M, et al. Establishing aluminium contact allergy. Contact Dermatitis. 2012;67:162-170.
  29. Bergfors E, Inerot A, Falk L, et al. Patch testing children with aluminium chloride hexahydrate in petrolatum: a review and a recommendation. Contact Dermatitis. 2019;81:81-88.
  30. Bruze M, Mowitz M, Netterlid E, et al. Patch testing with aluminum chloride hexahydrate in petrolatum. Contact Dermatitis. 2020;83:176-177.
  31. Hedberg YS, Wei Z, Matura M. Quantification of aluminium release from Finn Chambers under different in vitro test conditions of relevance for patch testing. Contact Dermatitis. 2020;83:380-386.
  32. King N, Moffitt D. Allergic contact dermatitis secondary to the use of aluminium Finn Chambers®. Contact Dermatitis. 2018;78:365-366.
  33. Rosholm Comstedt L, Dahlin J, Bruze M, et al. Patch testing with aluminium Finn Chambers could give false-positive reactions in patients with contact allergy to aluminium. Contact Dermatitis. 2021;85:407-414.
  34. Tran JM, Atwater AR, Reeder M. Patch testing in children: not just little adults. Cutis. 2019;104:288-290.
  35. Bergfors E, Trollfors B. Sixty-four children with persistent itching nodules and contact allergy to aluminium after vaccination with aluminium-adsorbed vaccines-prognosis and outcome after booster vaccination. Eur J Pediatr. 2013;172:171-177.
  36. Hoffmann SS, Thyssen JP, Elberling J, et al. Children with vaccination granulomas and aluminum contact allergy: evaluation of predispositions, avoidance behavior, and quality of life. Contact Dermatitis. 2020;83:99-107.
  37. Löffler P. Review: vaccine myth-buster-cleaning up with prejudices and dangerous misinformation [published online June 10, 2021]. Front Immunol. doi:10.3389/fimmu.2021.663280
  38. Salik E, Løvik I, Andersen KE, et al. Persistent skin reactions and aluminium hypersensitivity induced by childhood vaccines. Acta Derm Venereol. 2016;96:967-971.
  39. Beveridge MG, Polcari IC, Burns JL, et al. Local vaccine site reactions and contact allergy to aluminum. Pediatr Dermatol. 2012; 29:68-72.
  40. Frederiksen MS, Tofte H. Immunisation with aluminium-containing vaccine of a child with itching nodule following previous vaccination. Vaccine. 2004;23:1-2.
  41. Siemund I, Mowitz M, Zimerson E, et al. Variation in aluminium patch test reactivity over time. Contact Dermatitis. 2017;77:288-296.
  42. Lidholm AG, Bergfors E, Inerot A, et al. Unexpected loss of contact allergy to aluminium induced by vaccine. Contact Dermatitis. 2013;68:286.
Article PDF
CT110001021.PDF
Author and Disclosure Information

Ms. Novack is from the Icahn School of Medicine at Mount Sinai, New York, New York. Dr. Yu is from the Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston. Dr. Adler is from the Department of Dermatology, Keck School of Medicine, University of Southern California, Los Angeles.

Ms. Novack reports no conflict of interest. Dr. Yu is an immediate past member of the Board of Directors and chair of the Interactive Media Committee of the American Contact Dermatitis Society. He also has served as a speaker for the National Eczema Association and has received a research grant from the Dermatology Foundation. Dr. Adler has served as a research investigator and/or consultant for AbbVie and Skin Research Institute, LLC. He also is a member of the Board of Directors and chair of the CAMP Strategic Planning and Industry Support Committee of the American Contact Dermatitis Society.

The views expressed in this article are those of the authors and do not represent the views of the American Contact Dermatitis Society.

The eTable can be found in the Appendix online at www.mdedge.com/dermatology.

Correspondence: Brandon L. Adler, MD, 1441 Eastlake Ave, Ezralow Tower, Ste 5301, Los Angeles, CA 90033 (Brandon.Adler@med.usc.edu).

Issue
Cutis - 110(1)
Publications
MDedge Dermatology
Cutis
Topics
Contact Dermatitis
Page Number
21-24,E3
Sections
Contact Dermatitis
Author(s)
Danielle E. Novack, BA
Jiade Yu, MD
Brandon L. Adler, MD
Author(s)
Danielle E. Novack, BA
Jiade Yu, MD
Brandon L. Adler, MD
Author and Disclosure Information

Ms. Novack is from the Icahn School of Medicine at Mount Sinai, New York, New York. Dr. Yu is from the Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston. Dr. Adler is from the Department of Dermatology, Keck School of Medicine, University of Southern California, Los Angeles.

Ms. Novack reports no conflict of interest. Dr. Yu is an immediate past member of the Board of Directors and chair of the Interactive Media Committee of the American Contact Dermatitis Society. He also has served as a speaker for the National Eczema Association and has received a research grant from the Dermatology Foundation. Dr. Adler has served as a research investigator and/or consultant for AbbVie and Skin Research Institute, LLC. He also is a member of the Board of Directors and chair of the CAMP Strategic Planning and Industry Support Committee of the American Contact Dermatitis Society.

The views expressed in this article are those of the authors and do not represent the views of the American Contact Dermatitis Society.

The eTable can be found in the Appendix online at www.mdedge.com/dermatology.

Correspondence: Brandon L. Adler, MD, 1441 Eastlake Ave, Ezralow Tower, Ste 5301, Los Angeles, CA 90033 (Brandon.Adler@med.usc.edu).

Author and Disclosure Information

Ms. Novack is from the Icahn School of Medicine at Mount Sinai, New York, New York. Dr. Yu is from the Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston. Dr. Adler is from the Department of Dermatology, Keck School of Medicine, University of Southern California, Los Angeles.

Ms. Novack reports no conflict of interest. Dr. Yu is an immediate past member of the Board of Directors and chair of the Interactive Media Committee of the American Contact Dermatitis Society. He also has served as a speaker for the National Eczema Association and has received a research grant from the Dermatology Foundation. Dr. Adler has served as a research investigator and/or consultant for AbbVie and Skin Research Institute, LLC. He also is a member of the Board of Directors and chair of the CAMP Strategic Planning and Industry Support Committee of the American Contact Dermatitis Society.

The views expressed in this article are those of the authors and do not represent the views of the American Contact Dermatitis Society.

The eTable can be found in the Appendix online at www.mdedge.com/dermatology.

Correspondence: Brandon L. Adler, MD, 1441 Eastlake Ave, Ezralow Tower, Ste 5301, Los Angeles, CA 90033 (Brandon.Adler@med.usc.edu).

Article PDF
CT110001021.PDF
Article PDF
CT110001021.PDF

No time of the year is more exciting than the unveiling of the American Contact Dermatitis Society Allergen of the Year. Sometimes the selected allergen represents a completely novel cause of allergic contact dermatitis (ACD) with an unpronounceable chemical name. Not this time! The 2022 Allergen of the Year is likely to be lurking in your kitchen drawer at this very moment, as this year aluminum was chosen for this most prestigious honor.1 But do not throw out your aluminum foil just yet—aluminum allergy tends to be confined to specific scenarios. In this article, we highlight the growing recognition of aluminum contact allergy, particularly in the pediatric population, focusing on distinct presentations of aluminum ACD, unique sources of exposure, and nuances of patch testing to this metal.

Aluminum Is All Around Us

As the third most common element in the Earth’s crust, aluminum can be found quite literally everywhere.1 However, aluminum rarely is found in its pure elemental form; instead, it reacts with other elements around it, most commonly oxygen, to form aluminum-containing compounds. Known for their stability and safety, aluminum and its salts are incorporated in myriad products ranging from electronic equipment to foods and their packaging, medications, cosmetics, orthopedic and dental implants, and even tattoos. Aluminum also is found in the air and water supply and may even be encountered in certain workplaces, such as aircraft and machine industries. As such, contact with aluminum is all but certain in modern life.

The use of aluminum in consumer products is widely accepted as safe by public health agencies in the United States.2 Although there has been public concern that aluminum could be linked to development of breast cancer or Alzheimer disease, there is no clear evidence that these conditions are associated with routine aluminum exposure through ingestion or consumer products.3-5

Aluminum Contact Allergy

In part because of its ubiquity and in part because of the stability of aluminum-containing compounds, it was long thought that aluminum was nonallergenic. Contact allergy to elemental aluminum is rare; on the other hand, aluminum salts (the forms we are likely to encounter in daily life) are now recognized in the field of contact dermatitis as allergens of significance, particularly in the pediatric population.1,6

First reported as a possible occupational allergen in 1944,7 aluminum allergy came to prominence in the 1990s in association with vaccines. Aluminum is included in some vaccines as an adjuvant that bolsters the immune response8; the eTable lists currently available aluminum-containing vaccines in the United States; of note, none of the COVID-19 vaccines approved in the United States or Europe contain aluminum.11 Although the use of aluminum in vaccines is considered to be safe by the US Food and Drug Administration and Centers for Disease Control and Prevention,12,13 a small number of children become sensitized to aluminum through vaccines and may develop persistent pruritic subcutaneous nodules (also known as vaccination granulomas) at the injection site; however, the incidence of this adverse effect was less than 1% in large studies including as many as 76,000 children, suggesting that it is relatively rare.14,15 Upon patch testing, aluminum allergy has been detected in 77% to 95% of such cases.14 There is wide variation in the onset of the nodules ranging from weeks to years following vaccination.15 Due to pruritus, the examination may reveal accompanying excoriations, hyperpigmentation, and sometimes hypertrichosis at the injection site. Aluminum allergy related to vaccination also can manifest with widespread eruptions representing systemic contact dermatitis.16

Vaccines Containing Aluminum Adjuvants Currently Available in the United States

Along with vaccines, the second major source of aluminum sensitization is allergen-specific immunotherapies administered by allergists/immunologists, many of which contain aluminum hydroxide.17,18

On the consumer product front, antiperspirants are the most common source of cutaneous exposure to aluminum. Aluminum complexes react with electrolytes in sweat to form plugs in eccrine ducts, thereby preventing sweat excretion.6 Allergic contact dermatitis to these products presents with axillary-vault dermatitis. There also have been reports of ACD to aluminum in sunscreen and toothpaste, with the latter implicated in causing systemic ACD.19,20

 

 

Prevalence of Sensitization to Aluminum

There have been a few large-scale studies evaluating rates of sensitization to aluminum in general patch-test patient populations; additionally, because of the complexities of testing this metal, investigators have utilized differing formulations for patch testing. A recent Swedish study found that 0.9% of 5448 adults and 5.1% of 196 children showed positive reactions to aluminum chloride hexahydrate (ACH) 10% in petrolatum and/or aluminum lactate 12% in petrolatum.21 Notably, there was a significant association between aluminum allergy and history of atopy for both adults (P=.0056) and children (P=.046), which remains to be further explored. A systematic review and meta-analysis found comparable rates of aluminum allergy in 0.4% of adults and 5.6% of children without vaccine granulomas who were tested.22 With this evidence in mind, it has been recommended by contact dermatitis experts that aluminum be included in pediatric baseline patch test series and also investigated for potential inclusion in baseline series for adults.1

Differential Diagnosis of Aluminum ACD

The differential diagnosis for subcutaneous nodules following vaccination is broad and includes various forms of panniculitis, sarcoidosis, foreign body reactions, vascular malformations, infections, and malignancies.23-25 The diagnosis may be obscured in cases with delayed onset. Biopsy is not mandatory to establish the diagnosis; although variable histopathologic findings have been reported, a common feature is histiocytes with abundant granular cytoplasm.26 It may be possible to demonstrate the presence of aluminum particles in tissue using electron microscopy and X-ray microanalysis.

For those patients who present with axillary-vault dermatitis, the differential includes ACD to more common allergens in antiperspirants (eg, fragrance), as well as other axillary dermatoses including inverse psoriasis, erythrasma, Hailey-Hailey disease, and various forms of intertrigo. Dermatitis localized to the axillary rim suggests textile allergy.

Patch Testing to Aluminum

Due to its physicochemical properties, patch testing for aluminum allergy is complicated, and historically there has been a lack of consensus on the ideal test formulation.1,27,28 At this time, it appears that the most sensitive formulation for patch testing to aluminum is ACH 10% in petrolatum.1 Some contact dermatitis experts recommend that children younger than 8 years should be tested with ACH 2% in petrolatum to minimize the risk of extreme patch test reactions.29,30 In some patients sensitized to aluminum, the use of aluminum patch test chambers has been noted to produce false-positive reactions, taking the form of multiple ring-shaped reactions to the chambers themselves or reactions to certain allergens whose chemical properties cause corrosion of the aluminum within the chambers.31-33 Therefore, when testing for suspected aluminum allergy, plastic chambers should be used; given the higher prevalence of aluminum allergy in children, some clinics routinely use plastic chambers for all pediatric patch testing.34 Importantly, elemental aluminum, including empty aluminum test chambers or aluminum foil, alone is not sufficient for patch testing as it lacks sensitivity.1 Additionally, nearly 20% of positive tests will be missed if a day 7 reading is not performed, making delayed reading a must in cases with high suspicion for aluminum allergy.21

Management of Aluminum Allergy

The development of pruritic subcutaneous nodules is uncomfortable for children and their guardians alike and may be associated with prolonged symptoms that negatively impact quality of life35,36; nonetheless, expert authorities have determined that the preventive benefits of childhood vaccination far outweigh any risk posed by the presence of aluminum in vaccines.12,13,37 Because aluminum-free formulations may not be available for all vaccines, it is essential to educate patients and families who may be at risk for developing vaccine hesitancy or avoidance.35,36,38 Given the hypothesis that epidermal dendritic cells mediate aluminum sensitization, it has been proposed that vaccine administration via deep intramuscular rather than subcutaneous injection may mitigate the risk, but more evidence is needed to support this approach.39,40 The good news is that the nodules tend to fade with age, with a median time to resolution of 18 to 49 months.14 In addition, patients may experience loss of sensitization to aluminum over time41; in one study, 77% of 241 children lost patch test reactivity when retested 5 to 9 years later.42 The exact reason for this diminishment of reactivity is not well understood. Adjunctive treatments to relieve symptoms of vaccine granulomas include topical and intralesional corticosteroids and antihistamines.

For patients reacting to aluminum in antiperspirants, there are many aluminum-free formulations on the market as well as recipes for homemade antiperspirants.6 On a case-by-case basis, patients may need to avoid aluminum-containing medications, permanent tattoos, and orthopedic or dental implants. To the best of our knowledge, there is no evidence suggesting a need to avoid aluminum in foods and their containers in routine daily life; although some patients report exacerbations of their symptoms associated with food-related aluminum exposures (eg, canned food, dried fruit) and improvement with dietary modification, further investigation is needed to confirm the relevance of these sources of contact.36,38 For patients who require allergen-specific immunotherapy, aluminum-free allergen extracts are available.6

Final Interpretation

Exposure to aluminum is ubiquitous; although relatively uncommon, awareness of the potential for ACD to aluminum is increasingly important, particularly in children. Given the prevalence of aluminum contact allergy, it has been recommended by contact dermatitis experts for inclusion in baseline pediatric patch test series.1 Although it is a complex issue, the development of ACD in a small proportion of children exposed to aluminum in vaccines does not outweigh the benefit of vaccination for almost all children. When conducting patch testing to aluminum, studies support testing to ACH 10% in petrolatum for adults, and consider reducing the concentration to ACH 2% for children.

Acknowledgment—The authors thank Ian Fritz, MD (South Portland, Maine), for his critical input during preparation of this article.

No time of the year is more exciting than the unveiling of the American Contact Dermatitis Society Allergen of the Year. Sometimes the selected allergen represents a completely novel cause of allergic contact dermatitis (ACD) with an unpronounceable chemical name. Not this time! The 2022 Allergen of the Year is likely to be lurking in your kitchen drawer at this very moment, as this year aluminum was chosen for this most prestigious honor.1 But do not throw out your aluminum foil just yet—aluminum allergy tends to be confined to specific scenarios. In this article, we highlight the growing recognition of aluminum contact allergy, particularly in the pediatric population, focusing on distinct presentations of aluminum ACD, unique sources of exposure, and nuances of patch testing to this metal.

Aluminum Is All Around Us

As the third most common element in the Earth’s crust, aluminum can be found quite literally everywhere.1 However, aluminum rarely is found in its pure elemental form; instead, it reacts with other elements around it, most commonly oxygen, to form aluminum-containing compounds. Known for their stability and safety, aluminum and its salts are incorporated in myriad products ranging from electronic equipment to foods and their packaging, medications, cosmetics, orthopedic and dental implants, and even tattoos. Aluminum also is found in the air and water supply and may even be encountered in certain workplaces, such as aircraft and machine industries. As such, contact with aluminum is all but certain in modern life.

The use of aluminum in consumer products is widely accepted as safe by public health agencies in the United States.2 Although there has been public concern that aluminum could be linked to development of breast cancer or Alzheimer disease, there is no clear evidence that these conditions are associated with routine aluminum exposure through ingestion or consumer products.3-5

Aluminum Contact Allergy

In part because of its ubiquity and in part because of the stability of aluminum-containing compounds, it was long thought that aluminum was nonallergenic. Contact allergy to elemental aluminum is rare; on the other hand, aluminum salts (the forms we are likely to encounter in daily life) are now recognized in the field of contact dermatitis as allergens of significance, particularly in the pediatric population.1,6

First reported as a possible occupational allergen in 1944,7 aluminum allergy came to prominence in the 1990s in association with vaccines. Aluminum is included in some vaccines as an adjuvant that bolsters the immune response8; the eTable lists currently available aluminum-containing vaccines in the United States; of note, none of the COVID-19 vaccines approved in the United States or Europe contain aluminum.11 Although the use of aluminum in vaccines is considered to be safe by the US Food and Drug Administration and Centers for Disease Control and Prevention,12,13 a small number of children become sensitized to aluminum through vaccines and may develop persistent pruritic subcutaneous nodules (also known as vaccination granulomas) at the injection site; however, the incidence of this adverse effect was less than 1% in large studies including as many as 76,000 children, suggesting that it is relatively rare.14,15 Upon patch testing, aluminum allergy has been detected in 77% to 95% of such cases.14 There is wide variation in the onset of the nodules ranging from weeks to years following vaccination.15 Due to pruritus, the examination may reveal accompanying excoriations, hyperpigmentation, and sometimes hypertrichosis at the injection site. Aluminum allergy related to vaccination also can manifest with widespread eruptions representing systemic contact dermatitis.16

Vaccines Containing Aluminum Adjuvants Currently Available in the United States

Along with vaccines, the second major source of aluminum sensitization is allergen-specific immunotherapies administered by allergists/immunologists, many of which contain aluminum hydroxide.17,18

On the consumer product front, antiperspirants are the most common source of cutaneous exposure to aluminum. Aluminum complexes react with electrolytes in sweat to form plugs in eccrine ducts, thereby preventing sweat excretion.6 Allergic contact dermatitis to these products presents with axillary-vault dermatitis. There also have been reports of ACD to aluminum in sunscreen and toothpaste, with the latter implicated in causing systemic ACD.19,20

 

 

Prevalence of Sensitization to Aluminum

There have been a few large-scale studies evaluating rates of sensitization to aluminum in general patch-test patient populations; additionally, because of the complexities of testing this metal, investigators have utilized differing formulations for patch testing. A recent Swedish study found that 0.9% of 5448 adults and 5.1% of 196 children showed positive reactions to aluminum chloride hexahydrate (ACH) 10% in petrolatum and/or aluminum lactate 12% in petrolatum.21 Notably, there was a significant association between aluminum allergy and history of atopy for both adults (P=.0056) and children (P=.046), which remains to be further explored. A systematic review and meta-analysis found comparable rates of aluminum allergy in 0.4% of adults and 5.6% of children without vaccine granulomas who were tested.22 With this evidence in mind, it has been recommended by contact dermatitis experts that aluminum be included in pediatric baseline patch test series and also investigated for potential inclusion in baseline series for adults.1

Differential Diagnosis of Aluminum ACD

The differential diagnosis for subcutaneous nodules following vaccination is broad and includes various forms of panniculitis, sarcoidosis, foreign body reactions, vascular malformations, infections, and malignancies.23-25 The diagnosis may be obscured in cases with delayed onset. Biopsy is not mandatory to establish the diagnosis; although variable histopathologic findings have been reported, a common feature is histiocytes with abundant granular cytoplasm.26 It may be possible to demonstrate the presence of aluminum particles in tissue using electron microscopy and X-ray microanalysis.

For those patients who present with axillary-vault dermatitis, the differential includes ACD to more common allergens in antiperspirants (eg, fragrance), as well as other axillary dermatoses including inverse psoriasis, erythrasma, Hailey-Hailey disease, and various forms of intertrigo. Dermatitis localized to the axillary rim suggests textile allergy.

Patch Testing to Aluminum

Due to its physicochemical properties, patch testing for aluminum allergy is complicated, and historically there has been a lack of consensus on the ideal test formulation.1,27,28 At this time, it appears that the most sensitive formulation for patch testing to aluminum is ACH 10% in petrolatum.1 Some contact dermatitis experts recommend that children younger than 8 years should be tested with ACH 2% in petrolatum to minimize the risk of extreme patch test reactions.29,30 In some patients sensitized to aluminum, the use of aluminum patch test chambers has been noted to produce false-positive reactions, taking the form of multiple ring-shaped reactions to the chambers themselves or reactions to certain allergens whose chemical properties cause corrosion of the aluminum within the chambers.31-33 Therefore, when testing for suspected aluminum allergy, plastic chambers should be used; given the higher prevalence of aluminum allergy in children, some clinics routinely use plastic chambers for all pediatric patch testing.34 Importantly, elemental aluminum, including empty aluminum test chambers or aluminum foil, alone is not sufficient for patch testing as it lacks sensitivity.1 Additionally, nearly 20% of positive tests will be missed if a day 7 reading is not performed, making delayed reading a must in cases with high suspicion for aluminum allergy.21

Management of Aluminum Allergy

The development of pruritic subcutaneous nodules is uncomfortable for children and their guardians alike and may be associated with prolonged symptoms that negatively impact quality of life35,36; nonetheless, expert authorities have determined that the preventive benefits of childhood vaccination far outweigh any risk posed by the presence of aluminum in vaccines.12,13,37 Because aluminum-free formulations may not be available for all vaccines, it is essential to educate patients and families who may be at risk for developing vaccine hesitancy or avoidance.35,36,38 Given the hypothesis that epidermal dendritic cells mediate aluminum sensitization, it has been proposed that vaccine administration via deep intramuscular rather than subcutaneous injection may mitigate the risk, but more evidence is needed to support this approach.39,40 The good news is that the nodules tend to fade with age, with a median time to resolution of 18 to 49 months.14 In addition, patients may experience loss of sensitization to aluminum over time41; in one study, 77% of 241 children lost patch test reactivity when retested 5 to 9 years later.42 The exact reason for this diminishment of reactivity is not well understood. Adjunctive treatments to relieve symptoms of vaccine granulomas include topical and intralesional corticosteroids and antihistamines.

For patients reacting to aluminum in antiperspirants, there are many aluminum-free formulations on the market as well as recipes for homemade antiperspirants.6 On a case-by-case basis, patients may need to avoid aluminum-containing medications, permanent tattoos, and orthopedic or dental implants. To the best of our knowledge, there is no evidence suggesting a need to avoid aluminum in foods and their containers in routine daily life; although some patients report exacerbations of their symptoms associated with food-related aluminum exposures (eg, canned food, dried fruit) and improvement with dietary modification, further investigation is needed to confirm the relevance of these sources of contact.36,38 For patients who require allergen-specific immunotherapy, aluminum-free allergen extracts are available.6

Final Interpretation

Exposure to aluminum is ubiquitous; although relatively uncommon, awareness of the potential for ACD to aluminum is increasingly important, particularly in children. Given the prevalence of aluminum contact allergy, it has been recommended by contact dermatitis experts for inclusion in baseline pediatric patch test series.1 Although it is a complex issue, the development of ACD in a small proportion of children exposed to aluminum in vaccines does not outweigh the benefit of vaccination for almost all children. When conducting patch testing to aluminum, studies support testing to ACH 10% in petrolatum for adults, and consider reducing the concentration to ACH 2% for children.

Acknowledgment—The authors thank Ian Fritz, MD (South Portland, Maine), for his critical input during preparation of this article.

References
  1. Bruze M, Netterlid E, Siemund I. Aluminum—Allergen of the Year 2022. Dermatitis. 2022;33:10-15.
  2. Toxicological profile for aluminum. Agency for Toxic Substances and Disease Registry website. Accessed June 22, 2022. https://wwwn.cdc.gov/TSP/ToxProfiles/ToxProfiles.aspx?id=191&tid=34
  3. Klotz K, Weistenhöfer W, Neff F, et al. The health effects of aluminum exposure. Dtsch Arztebl Int. 2017;114:653-659.
  4. Liszewski W, Zaidi AJ, Fournier E, et al. Review of aluminum, paraben, and sulfate product disclaimers on personal care products [published online June 16, 2021]. J Am Acad Dermatol. doi:10.1016/j. jaad.2021.06.840
  5. Van Dyke N, Yenugadhati N, Birkett NJ, et al. Association between aluminum in drinking water and incident Alzheimer’s disease in the Canadian Study of Health and Aging cohort. Neurotoxicology. 2021;83:157-165.
  6. Kullberg SA, Ward JM, Liou YL, et al. Cutaneous reactions to aluminum. Dermatitis. 2020;31:335-349.
  7. Hall AF. Occupational contact dermatitis among aircraft workers. J Am Med Assoc. 1944;125:179-185.
  8. HogenEsch H. Mechanism of immunopotentiation and safety of aluminum adjuvants. Front Immunol. 2012;3:406.
  9. Vaccine exipient summary. Centers for Disease Control and Prevention website. Published November 2021. Accessed June 22, 2022. https://www.cdc.gov/vaccines/pubs/pinkbook/downloads/appendices/b/excipient-table-2.pdf
  10. Vaccines licensed for use in the United States. US Food and Drug Administration website. Updated January 31, 2022. Accessed June 22, 2022. https://www.fda.gov/vaccines-blood-biologics/vaccines/vaccines-licensed-use-united-states
  11. Swenson A. US and EU COVID vaccines don’t contain aluminum. AP News. Published March 16, 2021. Accessed June 22, 2022. https://apnews.com/article/fact-checking-afs:Content:9991020426
  12. Adjuvants and vaccines. Centers for Disease Control and Prevention website. Updated August 4, 2020. Accessed June 22, 2022. https://www.cdc.gov/vaccinesafety/concerns/adjuvants.html
  13. Common ingredients in U.S. licensed vaccines. US Food and Drug Administration website. Updated April 19, 2019. Accessed June 22, 2002. https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/common-ingredients-us-licensed-vaccines
  14. Bergfors E, Hermansson G, Nyström Kronander U, et al. How common are long-lasting, intensely itching vaccination granulomas and contact allergy to aluminium induced by currently used pediatric vaccines? a prospective cohort study. Eur J Pediatr. 2014;173:1297-1307.
  15. Bergfors E, Trollfors B, Inerot A. Unexpectedly high incidence of persistent itching nodules and delayed hypersensitivity to aluminium in children after the use of adsorbed vaccines from a single manufacturer. Vaccine. 2003;22:64-69.
  16. Mistry BD, DeKoven JG. Widespread cutaneous eruption after aluminum-containing vaccination: a case report and review of current literature. Pediatr Dermatol. 2021;38:872-874.
  17. Netterlid E, Hindsén M, Björk J, et al. There is an association between contact allergy to aluminium and persistent subcutaneous nodules in children undergoing hyposensitization therapy. Contact Dermatitis. 2009;60:41-49.
  18. Netterlid E, Hindsén M, Siemund I, et al. Does allergen-specific immunotherapy induce contact allergy to aluminium? Acta Derm Venereol. 2013;93:50-56.
  19. Hoffmann SS, Elberling J, Thyssen JP, et al. Does aluminium in sunscreens cause dermatitis in children with aluminium contact allergy: a repeated open application test study. Contact Dermatitis. 2022;86:9-14.
  20. Veien NK, Hattel T, Laurberg G. Systemically aggravated contact dermatitis caused by aluminium in toothpaste. Contact Dermatitis. 1993;28:199-200.
  21. Siemund I, Dahlin J, Hindsén M, et al. Contact allergy to two aluminum salts in consecutively patch-tested dermatitis patients. Dermatitis. 2022;33:31-35.
  22. Hoffmann SS, Wennervaldt M, Alinaghi F, et al. Aluminium contact allergy without vaccination granulomas: a systematic review and metaanalysis. Contact Dermatitis. 2021;85:129-135.
  23. Bergfors E, Lundmark K, Kronander UN. Case report: a child with a long-standing, intensely itching subcutaneous nodule on a thigh: an uncommon (?) reaction to commonly used vaccines [published online January 13, 2013]. BMJ Case Rep. doi:10.1136/bcr-2012-007779
  24. Mooser G, Gall H, Weber L, et al. Cold panniculitis—an unusual differential diagnosis from aluminium allergy in a patient hyposensitized with aluminium-precipitated antigen extract. Contact Dermatitis. 2001;44:366-375.
  25. Mulholland D, Joyce EA, Foran A, et al. The evaluation of palpable thigh nodularity in vaccination-age children—differentiating vaccination granulomas from other causes. J Med Ultrasound. 2021;29:129.
  26. Chong H, Brady K, Metze D, et al. Persistent nodules at injection sites (aluminium granuloma)—clinicopathological study of 14 cases with a diverse range of histological reaction patterns. Histopathology. 2006;48:182-188.
  27. Nikpour S, Hedberg YS. Using chemical speciation modelling to discuss variations in patch test reactions to different aluminium and chromium salts. Contact Dermatitis. 2021;85:415-420.
  28. Siemund I, Zimerson E, Hindsén M, et al. Establishing aluminium contact allergy. Contact Dermatitis. 2012;67:162-170.
  29. Bergfors E, Inerot A, Falk L, et al. Patch testing children with aluminium chloride hexahydrate in petrolatum: a review and a recommendation. Contact Dermatitis. 2019;81:81-88.
  30. Bruze M, Mowitz M, Netterlid E, et al. Patch testing with aluminum chloride hexahydrate in petrolatum. Contact Dermatitis. 2020;83:176-177.
  31. Hedberg YS, Wei Z, Matura M. Quantification of aluminium release from Finn Chambers under different in vitro test conditions of relevance for patch testing. Contact Dermatitis. 2020;83:380-386.
  32. King N, Moffitt D. Allergic contact dermatitis secondary to the use of aluminium Finn Chambers®. Contact Dermatitis. 2018;78:365-366.
  33. Rosholm Comstedt L, Dahlin J, Bruze M, et al. Patch testing with aluminium Finn Chambers could give false-positive reactions in patients with contact allergy to aluminium. Contact Dermatitis. 2021;85:407-414.
  34. Tran JM, Atwater AR, Reeder M. Patch testing in children: not just little adults. Cutis. 2019;104:288-290.
  35. Bergfors E, Trollfors B. Sixty-four children with persistent itching nodules and contact allergy to aluminium after vaccination with aluminium-adsorbed vaccines-prognosis and outcome after booster vaccination. Eur J Pediatr. 2013;172:171-177.
  36. Hoffmann SS, Thyssen JP, Elberling J, et al. Children with vaccination granulomas and aluminum contact allergy: evaluation of predispositions, avoidance behavior, and quality of life. Contact Dermatitis. 2020;83:99-107.
  37. Löffler P. Review: vaccine myth-buster-cleaning up with prejudices and dangerous misinformation [published online June 10, 2021]. Front Immunol. doi:10.3389/fimmu.2021.663280
  38. Salik E, Løvik I, Andersen KE, et al. Persistent skin reactions and aluminium hypersensitivity induced by childhood vaccines. Acta Derm Venereol. 2016;96:967-971.
  39. Beveridge MG, Polcari IC, Burns JL, et al. Local vaccine site reactions and contact allergy to aluminum. Pediatr Dermatol. 2012; 29:68-72.
  40. Frederiksen MS, Tofte H. Immunisation with aluminium-containing vaccine of a child with itching nodule following previous vaccination. Vaccine. 2004;23:1-2.
  41. Siemund I, Mowitz M, Zimerson E, et al. Variation in aluminium patch test reactivity over time. Contact Dermatitis. 2017;77:288-296.
  42. Lidholm AG, Bergfors E, Inerot A, et al. Unexpected loss of contact allergy to aluminium induced by vaccine. Contact Dermatitis. 2013;68:286.
References
  1. Bruze M, Netterlid E, Siemund I. Aluminum—Allergen of the Year 2022. Dermatitis. 2022;33:10-15.
  2. Toxicological profile for aluminum. Agency for Toxic Substances and Disease Registry website. Accessed June 22, 2022. https://wwwn.cdc.gov/TSP/ToxProfiles/ToxProfiles.aspx?id=191&tid=34
  3. Klotz K, Weistenhöfer W, Neff F, et al. The health effects of aluminum exposure. Dtsch Arztebl Int. 2017;114:653-659.
  4. Liszewski W, Zaidi AJ, Fournier E, et al. Review of aluminum, paraben, and sulfate product disclaimers on personal care products [published online June 16, 2021]. J Am Acad Dermatol. doi:10.1016/j. jaad.2021.06.840
  5. Van Dyke N, Yenugadhati N, Birkett NJ, et al. Association between aluminum in drinking water and incident Alzheimer’s disease in the Canadian Study of Health and Aging cohort. Neurotoxicology. 2021;83:157-165.
  6. Kullberg SA, Ward JM, Liou YL, et al. Cutaneous reactions to aluminum. Dermatitis. 2020;31:335-349.
  7. Hall AF. Occupational contact dermatitis among aircraft workers. J Am Med Assoc. 1944;125:179-185.
  8. HogenEsch H. Mechanism of immunopotentiation and safety of aluminum adjuvants. Front Immunol. 2012;3:406.
  9. Vaccine exipient summary. Centers for Disease Control and Prevention website. Published November 2021. Accessed June 22, 2022. https://www.cdc.gov/vaccines/pubs/pinkbook/downloads/appendices/b/excipient-table-2.pdf
  10. Vaccines licensed for use in the United States. US Food and Drug Administration website. Updated January 31, 2022. Accessed June 22, 2022. https://www.fda.gov/vaccines-blood-biologics/vaccines/vaccines-licensed-use-united-states
  11. Swenson A. US and EU COVID vaccines don’t contain aluminum. AP News. Published March 16, 2021. Accessed June 22, 2022. https://apnews.com/article/fact-checking-afs:Content:9991020426
  12. Adjuvants and vaccines. Centers for Disease Control and Prevention website. Updated August 4, 2020. Accessed June 22, 2022. https://www.cdc.gov/vaccinesafety/concerns/adjuvants.html
  13. Common ingredients in U.S. licensed vaccines. US Food and Drug Administration website. Updated April 19, 2019. Accessed June 22, 2002. https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/common-ingredients-us-licensed-vaccines
  14. Bergfors E, Hermansson G, Nyström Kronander U, et al. How common are long-lasting, intensely itching vaccination granulomas and contact allergy to aluminium induced by currently used pediatric vaccines? a prospective cohort study. Eur J Pediatr. 2014;173:1297-1307.
  15. Bergfors E, Trollfors B, Inerot A. Unexpectedly high incidence of persistent itching nodules and delayed hypersensitivity to aluminium in children after the use of adsorbed vaccines from a single manufacturer. Vaccine. 2003;22:64-69.
  16. Mistry BD, DeKoven JG. Widespread cutaneous eruption after aluminum-containing vaccination: a case report and review of current literature. Pediatr Dermatol. 2021;38:872-874.
  17. Netterlid E, Hindsén M, Björk J, et al. There is an association between contact allergy to aluminium and persistent subcutaneous nodules in children undergoing hyposensitization therapy. Contact Dermatitis. 2009;60:41-49.
  18. Netterlid E, Hindsén M, Siemund I, et al. Does allergen-specific immunotherapy induce contact allergy to aluminium? Acta Derm Venereol. 2013;93:50-56.
  19. Hoffmann SS, Elberling J, Thyssen JP, et al. Does aluminium in sunscreens cause dermatitis in children with aluminium contact allergy: a repeated open application test study. Contact Dermatitis. 2022;86:9-14.
  20. Veien NK, Hattel T, Laurberg G. Systemically aggravated contact dermatitis caused by aluminium in toothpaste. Contact Dermatitis. 1993;28:199-200.
  21. Siemund I, Dahlin J, Hindsén M, et al. Contact allergy to two aluminum salts in consecutively patch-tested dermatitis patients. Dermatitis. 2022;33:31-35.
  22. Hoffmann SS, Wennervaldt M, Alinaghi F, et al. Aluminium contact allergy without vaccination granulomas: a systematic review and metaanalysis. Contact Dermatitis. 2021;85:129-135.
  23. Bergfors E, Lundmark K, Kronander UN. Case report: a child with a long-standing, intensely itching subcutaneous nodule on a thigh: an uncommon (?) reaction to commonly used vaccines [published online January 13, 2013]. BMJ Case Rep. doi:10.1136/bcr-2012-007779
  24. Mooser G, Gall H, Weber L, et al. Cold panniculitis—an unusual differential diagnosis from aluminium allergy in a patient hyposensitized with aluminium-precipitated antigen extract. Contact Dermatitis. 2001;44:366-375.
  25. Mulholland D, Joyce EA, Foran A, et al. The evaluation of palpable thigh nodularity in vaccination-age children—differentiating vaccination granulomas from other causes. J Med Ultrasound. 2021;29:129.
  26. Chong H, Brady K, Metze D, et al. Persistent nodules at injection sites (aluminium granuloma)—clinicopathological study of 14 cases with a diverse range of histological reaction patterns. Histopathology. 2006;48:182-188.
  27. Nikpour S, Hedberg YS. Using chemical speciation modelling to discuss variations in patch test reactions to different aluminium and chromium salts. Contact Dermatitis. 2021;85:415-420.
  28. Siemund I, Zimerson E, Hindsén M, et al. Establishing aluminium contact allergy. Contact Dermatitis. 2012;67:162-170.
  29. Bergfors E, Inerot A, Falk L, et al. Patch testing children with aluminium chloride hexahydrate in petrolatum: a review and a recommendation. Contact Dermatitis. 2019;81:81-88.
  30. Bruze M, Mowitz M, Netterlid E, et al. Patch testing with aluminum chloride hexahydrate in petrolatum. Contact Dermatitis. 2020;83:176-177.
  31. Hedberg YS, Wei Z, Matura M. Quantification of aluminium release from Finn Chambers under different in vitro test conditions of relevance for patch testing. Contact Dermatitis. 2020;83:380-386.
  32. King N, Moffitt D. Allergic contact dermatitis secondary to the use of aluminium Finn Chambers®. Contact Dermatitis. 2018;78:365-366.
  33. Rosholm Comstedt L, Dahlin J, Bruze M, et al. Patch testing with aluminium Finn Chambers could give false-positive reactions in patients with contact allergy to aluminium. Contact Dermatitis. 2021;85:407-414.
  34. Tran JM, Atwater AR, Reeder M. Patch testing in children: not just little adults. Cutis. 2019;104:288-290.
  35. Bergfors E, Trollfors B. Sixty-four children with persistent itching nodules and contact allergy to aluminium after vaccination with aluminium-adsorbed vaccines-prognosis and outcome after booster vaccination. Eur J Pediatr. 2013;172:171-177.
  36. Hoffmann SS, Thyssen JP, Elberling J, et al. Children with vaccination granulomas and aluminum contact allergy: evaluation of predispositions, avoidance behavior, and quality of life. Contact Dermatitis. 2020;83:99-107.
  37. Löffler P. Review: vaccine myth-buster-cleaning up with prejudices and dangerous misinformation [published online June 10, 2021]. Front Immunol. doi:10.3389/fimmu.2021.663280
  38. Salik E, Løvik I, Andersen KE, et al. Persistent skin reactions and aluminium hypersensitivity induced by childhood vaccines. Acta Derm Venereol. 2016;96:967-971.
  39. Beveridge MG, Polcari IC, Burns JL, et al. Local vaccine site reactions and contact allergy to aluminum. Pediatr Dermatol. 2012; 29:68-72.
  40. Frederiksen MS, Tofte H. Immunisation with aluminium-containing vaccine of a child with itching nodule following previous vaccination. Vaccine. 2004;23:1-2.
  41. Siemund I, Mowitz M, Zimerson E, et al. Variation in aluminium patch test reactivity over time. Contact Dermatitis. 2017;77:288-296.
  42. Lidholm AG, Bergfors E, Inerot A, et al. Unexpected loss of contact allergy to aluminium induced by vaccine. Contact Dermatitis. 2013;68:286.
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Aluminum: The 2022 American Contact Dermatitis Society Allergen of the Year
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Practice Points

  • Aluminum is an allergen of significance relating to its use in vaccines, immunotherapies, and antiperspirants.
  • There is a greater prevalence of aluminum contact allergy in children than in adults, affecting up to 5% of the pediatric patch-test population.
  • The recommended patch test formulation is aluminum chloride hexahydrate 10% in petrolatum, with consideration of reducing the concentration to 2% in children younger than 8 years to avoid strong reactions.
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