Introduction

Calendula officinalis is a plant of the Asteraceae family. Extract from this plant have been used for traditional medicinal uses and suggested for many therapeutic uses such as: anti-inflammatory, anti-tumor-promoting, and cytotoxic activities [1]. Chemical constituents of Calendula include sugars, carotenoids, phenolic acids, sterols, saponins, flavonoids, resins, sterins, quinones, mucilages, vitamins, polyprenylquinones, and essential oils [2]. Assessment of therapeutic indications performed by the European Medicines Agency (EMA) recognized the traditional medicinal use of Calendula officinalis products for the following two indications: symptomatic treatment of minor inflammations of the skin (such as sunburn) and as an aid in healing of minor wounds; symptomatic treatment of minor inflammations in the mouth or the throat [3]. Preclinical experiments conducted on rodents indicate that the extract possesses an acceptable toxic profile. The dried flowers have been also used as a spice and is considered to be generally recognized to be safe [4], however minimal ocular irritation was seen with one formulation in the laboratory animal [5]. Calendula Officinalis extract is reported to be used in almost 200 cosmetic formulations, over a wide range of product categories [6]. Although data on dermal irritation and sensitization of CF and CFE’s are available, the risk of subchronic systemic toxicity following dermal application has not been evaluated. The threshold of toxicological concern (TTC) is a pragmatic, risk assessment based approach that has gained regulatory acceptance for food and has been recently adapted to address cosmetic ingredient safety [7].

Case Description

We describe a case of a 12 year old girl forced to the hospital for an acute bilateral periocular erythema and eczema after use for two days of Calendula Officinalis compresses on the eyes for the treatment of an episode of conjunctivitis. The compresses were made with a cotton wool soaked in one tablespoon of a macerated oil (a preparation with Calendula Flowers wherein the solvent is oil-based) and three tablespoons of water. A familiar history of allergies or previous allergic diseases were denied. Then the patient underwent allergological investigation. Routine blood chemical tests were normal but total seric IgE were elevated. Skin Prick test to Asteraceae was positive (+++). Patch test 20% aqueous dilution of the product was applied on the surface of her left upper arm and reading was made after 48h and 72 hours with positive result (+ and +++ respectively). Treatment with the product has been withdrawn and it is not reused. Intensity of itching and severity of dermatitis were reduced in two-three days after topical therapy with steroids and systemic oral therapy with antihistaminic drugs, symptoms were completely resolved after two weeks. Assessment of causality relationship, according to the Naranjo algorythm (score 6) showed it as probable [8].

Discussion

Even though allergenic sesquiterpene lactones are amongst the chemicals contained in Calendula officinalis, until now Calendula extracts have been considered weakly sensitizing due to the scarcity of case reports until recently. This contradictory issue has been justified with the remark that sesquiterpene lactones are lacking in the flowers, the part of plant commonly used to obtain medicinal herbal preparations from calendula [9]. Scientific literature comprises only one case reporting of an anaphylactic shock caused by gargling with Calendula tincture [10], a different herbal preparation of the plant with respect to that used in the case here reported. While, it is possible, an IgE-mediated reaction for acute hypersensitivity and a cellular-mediate reaction for the delayed hypersensitivity. Likely, as it happens with a common allergen, House Dust Mite (Dermatophagoides), that are implicated at same time in various diseases like atopic dermatitis, asthma, rhinitis and perennial, with prick- and pathch- test positives. It has also been proven that patch testing with Dermatophagoides pteronyssinus (DP) is important for detection of contact sensitization in chronic dermatitis.

Conclusion

This is the first reporting of an adverse reaction linked to the use of Calendula officinalis in pediatric age. The use of Calendula extracts is very common in traditional medicine, as these products are highly available because sold in many countries as food supplements or medical devices. Moreover, different herbal preparations derived from Calendula are cosmetic ingredients currently used also in pediatric age, including the adolescents. Because it is not considered toxic even if adequate safety data of use in children and adolescents are lacking, we think that pediatric subjects and in particular in who is allergic to Asteraceae should be very careful to use Calendula derived products.