Fixed food eruption caused by mango (Mangifera indica)

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A 22-year-old woman visited dermatology outpatient department with flat brownish lesions on the trunk for 1 week. The lesions were associated with a mild burning sensation. In spite of repeated and detailed questioning, she denied intake of any drug preceding the onset of skin lesions. However, she gave a history of eating a mango one day before the onset of the lesions. On further questioning, she recalled developing similar cutaneous lesions at almost the same sites around 1year ago. This earlier episode had also occurred 1 day after eating a mango. None of the family members had similar complaints or a history of fixed drug eruption. Cutaneous examination revealed multiple, well-defined, round-to-oval, hyperpigmented to violaceous plaques with a peripheral rim of erythema on the chest, abdomen and back [Figure 1]. The surface of plaques had a rough, peau-d’-orange appearance. The plaques on the left side of the abdomen coalesced to form a large plaque of about 10×6 cm [Figure 2]. Examination of the oral cavity, palms, soles and genitalia showed no abnormality. Complete blood picture, renal function and liver function tests were within normal limits.

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Figure 1: Well defined, round to oval, hyperpigmented, dusky violaceous plaques with a peripheral rim of erythema.

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Figure 2: Large lesion from coalescence of smaller ones on the left side of the abdomen with rough, peau d’ orange surface.

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The clinical picture was strongly suggestive of a fixed drug eruption. However, as the patient denied any drug intake, a punch biopsy was taken from the lesion. Histopathology showed mild irregular acanthosis, hyperkeratosis and parakeratosis. The epidermis also showed basal vacuolar degeneration and numerous necrotic keratinocytes. The dermis showed perivascular infiltrate composed of lymphocytes, eosinophils, and plasma cells [Figure 3a and 3b]. In view of the clinicopathologic findings the provisional diagnosis was fixed food eruption (FFE). She was treated with oral prednisolone (40mg) (tapered over 4 weeks), topical betamethasone valerate cream, and oral cetirizine. About 3 months after the lesions resolved, an oral provocation test with one cup of mango pieces was conducted. Around 8 to 10 hours after consuming the mango, the patient started to develop a burning sensation followed by similar new lesions on the same sites of the body confirming FFE to mango. A patch test was not done as the patient did not give consent.

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Figure 3a: Hyperkeratosis, irregular acanthosis, numerous necrotic keratinocytes (black arrow) and interface dermatitis (Haematoxylin and eosin, 100x).

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Figure 3b: Dermal perivascular infiltrate composed of lymphocytes, eosinophils and a few plasma cells (Haematoxylin and eosin, 400x).

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Fixed drug eruption is a common entity characterised by single or multiple erythematous lesions developing at the same site on re-exposure to the offending drug. When the causative agent is a food item, it is termed as FFE. The term FFE was coined by Kelso in 1996, when it developed due to strawberries.¹ FFE typically presents with erythematous or dusky violaceous macules or plaques within 12 to 24 hours of food intake and these lesions slowly resolve with post inflammatory hyperpigmentation.² The exact pathophysiology of FFE is not known. Type IV hypersensitivity reaction in FFE is known to be mediated by intraepidermal CD8⁺ T‐cells. Due to genetic susceptibility, the patient first gets sensitised to intermittent intake of the offending food, like the mango in our case. The chemicals in mango, like mangiferin and/or mangol, act as antigens and activate the intraepidermal CD8⁺ T‐cells. These activated CD8⁺ T-cells transform morphologically into natural killer cells, release large amounts of Interferon gamma and tumour necrosis factor alpha that lead to keratinocyte necrosis through the granzyme B, porin, or Fas ligand pathway.³ On withdrawal of the offending food, the lesions slowly resolve with residual hyperpigmentation. Most of the CD8⁺ T-cells lose their natural killer morphology and attain a memory phenotype with expression of CD3, CD8, and CD11b. These cells remain dormant in the skin lesions. On re-exposure to the same offending food, these memory CD8⁺ T-cells get reactivated and release cytokines. This leads to keratinocyte apoptosis, necrosis and skin lesions at the same sites as earlier lesions. However, IgE-mediated process (type 1 hypersenstivity) has also been proposed due to the presence of urticarial skin lesions and eosinophils in the dermis. Few authors suggest that FFE is due to a combination of both type I and type IV reactions.^3-5

FFE has been reported to various food items like cheese, kiwi, peanuts, cashews, asparagus, strawberries, moringa, walnuts, hazelnuts and shellfish.^1,3,6 Fukushima et al;⁷ reported a case of FFE to cashewnut. 2S albumin protein, a vicilin-like protein found in cashew nuts, was identified as the allergen that activated the CD8⁺ T-cell pathway, leading to keratinocyte damage. Due to the presence of the same or similar allergen, the patient also showed cross-reactivity to other nuts like almonds, peanuts, and pignolia nuts. Sohn et al;³ described the first case of FFE to hardy kiwi leaves; the patient also showed cross-sensitivity to green kiwi fruit.

We report a case of FFE to mango, the national fruit of India, consumed throughout the country during summer. Though mango is a common fruit in India, our patient has reportedly eaten mango very occasionally, around 3 to 4 times before the development of the skin lesions. In genetically susceptible individuals, prior sensitisation is required for the development of lesions of fixed food/drug eruption. Sensitisation is known to occur more rapidly if the offending drug/food is consumed intermittently rather than continuously. The pulp of the mango fruit contains various chemicals, of which is a resorcinol called mangolis, known to cause allergic contact dermatitis.⁸ In susceptible individuals, these substances can act as antigens, triggering an immune reaction and activation of CD9⁺ T-cells, which migrate to the skin and result in the classical FFE lesion. The memory T-cells specific to mangiferin might remain in the affected skin site and reactivate on re-exposure to the fruit, leading to the lesions at the same site. FFE is diagnosed mainly by thorough and proper clinical history and the timing of onset of lesions after food intake. If in doubt, it can be further confirmed by skin biopsy, oral provocation testor patch test. Avoidance of the causative agent is the mainstay of treatment to prevent the recurrence of lesions. Topical corticosteroids and antihistamines are generally used in the management of FFE. However, in generalised or severe cases, oral steroids are needed.