Pruritic vesicles erupt on a boy’s legs


A healthy 12-year-old boy with eczema shows up at the office with an incredibly itchy rash on his legs that has exploded over the last 48 hours. He has a history of dry skin to which his mother regularly applies various moisturizers, including calendula oil.


A healthy 12-year-old boy with eczema shows up at the office with an incredibly itchy rash on his legs that has exploded over the last 48 hours. He has a history of dry skin to which his mother regularly applies various moisturizers, including calendula oil. 

NEXT: What's the diagnosis?




Used in Mediterranean countries for food and medicine since the Middle Ages, calendula oil is derived from the flowers or seeds of Calendula officinalis (pot marigold). Its high concentration of plant-based antioxidants, or flavonoids, protects against free radical damage and appears to be active against inflammation, bacteria, and viruses. It is most commonly applied to the skin for indications such as burns, cuts, bruises, and dermatitis, and is also found in cosmetic products. The extract can be derived from any part of the plant.1,2

Overall, allergic reactions to calendula have been rarely reported. The most convincing evidence comes from an Austrian study on suspected delayed allergic reactions, in which 9 of 443 patients (2%) proved to be sensitive to a short ether extract of marigold.3 Six recalled usage of marigold in an ointment or cream and 2 had contact dermatitis (CD) soon after using the product. 


In a review published by the European Medicines Agency, which conducts a systematic assessment of medicinal plants, the potential allergens in calendula are thought to be related to calendula’s phenolic acids and phenylpropanoids. These types of compounds have been previously found in other plants to be sensitizers or elicitors of CD.

Hypersensitivity develops when an innocuous substance becomes bound to cutaneous proteins, which then associate with major histocompatibility complex (MHC) class II antigens (MHC II) or bind directly to antigen-presenting cells such as Langerhans cells and epidermal dendritic cells. This T-cell recognition of the antigen leads to activation and proliferation of T-cells, which then leads to the production of inflammatory cytokines. Because of Fas ligand (FasL) and perforin expression, T-cells have an apoptotic effect on keratinocytes. The reaction peaks at 18 to 72 hours and then declines, which helps explain the clinical presentation of CD.3,4


Contact dermatitis can be divided into acute and chronic variants. In acute CD, patients present with erythema, edema, vesicles, oozing, and intense pruritus. They can also develop pruritic vesicles that burst quickly, leading to crusting and weeping. Typically, the distribution of the rash is associated with the areas of exposure to the allergen, although it is possible for allergens to reach other areas of the body by other routes such as autotransfer (ie, nail polish to the eyelids or neck by transfer of fingers) or heterotransfer (ie, transfer from another person).3 In chronic allergic contact dermatitis, hyperkeratosis, desquamation, lichenification, and fissuring become more prominent.

Next: Patch testing in atopic dermatitis

The differential diagnosis of CD is based on history of exposure as well as consideration of long-term exposure to an antigen because multiple exposures are needed for sensitization. Diagnosis can be confirmed by patch testing, biopsy, and blood tests.5 Treatment of CD involves avoidance of the allergen and use of topical class II or class III corticosteroids, such as mometasone furoate or betamethasone. Chronic allergic CD may respond to narrow band ultraviolet (UV)-B phototherapy or psoralen with UV-A (PUVA) treatments.3

As for this patient, all contact with calendula oil was discontinued. He began a 2-week tapering course of oral prednisone and cool tap water compresses, with dramatic improvement in the eruption and symptoms within 48 to 72 hours.



1. Calapai G, Miroddi M, Minciullo PL, Caputi AP, Gangemi S, Schmidt RJ. Contact dermatitis as an adverse reaction to some topically used European herbal medicinal products-part 1: Achillea millefolium-Curcuma longa. Contact Dermatitis. 2014;71(1):1-12.

2. Ehrlich SD. Complementary and alternative medicine guide: calendula. University of Maryland Medical Center. Available at: Accessed February 17, 2017.

3. Kostner L, Anzengruber F, Guillod C, Recher M, Schmid-Grendelmeier P, Navarini AA. Allergic contact dermatitis. Immunol Allergy Clin North Am. 2017;37(1):141-152.

4. Rustemeyer T, van Hoogstraten IMW, von Blomberg ME, Scheper RJ. Mechanisms in allergic contact dermatitis. In: Frosch PJ, Menné T, Lepoittevin JP, eds. Contact Dermatitis. 4th ed. Heidelberg: Springer-Verlag GmbH; 2006:11-43.

5. Yiannias J, Fowler J, Corona R. Clinical features and diagnosis of allergic contact dermatitis. UpToDate. Available at: Updated July 11, 2016. Accessed February 17, 2017.

Ms Wang is a fourth-year medical student at Johns Hopkins University School of Medicine, Baltimore, Maryland. Dr. Cohen, section editor for Dermcase, is professor of Pediatrics and Dermatology, Johns Hopkins University School of Medicine, Baltimore. The author and section editor have nothing to disclose in regard to affiliations with or financial interests in any organizations that may have an interest in any part of this article. Vignettes are based on real cases that have been modified to allow the author and editor to focus on key teaching points. Images also may be edited or substituted for teaching purposes.

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