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.