Anaphylactic shock with methylprednisolone, Kounis syndrome and hypersensitivity to corticosteroids: a clinical paradox

Corticosteroids are potent anti-inflammatory and immunomodulating agents which can:

Systemic corticosteroids can induce allergic reactions via the following mechanisms:

Succinate esters of hydrocortisone and methylprednisolone are the drugs that are most frequently responsible for type 1 (immediate) allergic reactions. Indeed, different affinities of hydrocortisone acetate, hydrocortisone sodium phosphate, and hydrocortisone sodium succinate to serum and cutaneous proteins have been demonstrated [8]. However, intravenous administration of 200 mg of hydrocortisone sodium phosphate, for treatment of status asthmaticus [9], has induced itching, macular rash, paresthesiae, tremor of the arms and legs, and nausea and vomiting in 16 patients suffering from chronic asthma.

The described patient had experienced anaphylaxis due to cow’s milk proteins administered through gastrostomy when he was 4 months old. Therefore he could be suffered an atopic diathesis. Atopic diathesis involves genetics, immune system dysfunction, environmental exposures, and difficulties with the permeability of the skin. It results from complex abnormalities of the innate and adaptive immune systems. This condition refers to an inherited tendency to produce IgE antibodies in response to small amounts of common environmental factors and atopic patients are easily developed an allergic reaction when they are exposed to such factors. Recent reports have shown that atopic patients suffering from systemic lupus erythematosus have more severe disease at diagnosis and poorer outcomes than SLE patients without atopy [10]. Furthermore, late-onset anaphylactic reactions following intravenous cyclophosphamide pulse in a patient with systemic sclerosis and systemic lupus erythematosus overlap syndrome have been also encountered [11]. Therefore, atopy seems to constitute a disease-substrate that predispose to allergic and anaphylactic reactions. Indeed, a 32-year-old woman suffering from atopic dermatitis [12], without any previous history of food or drug allergy, no suggestive family history, and no other systemic diseases, developed erythematous patches with slight elevation and itching on the face, trunk, and both hands after 0.7 mL of intralesional triamcinolone solution with concentration 2.5 mg/mL on her dorsum of both hands. Her symptoms worsened with therapeutic intravenous re-administration of dexamethasone and she recovered only after treatment with epinephrine

In another recent report, a 52-year-old female patient, without previous history of any illness, developed severe retrosternal pain with electrocardiographic ST depression at II, III, aVF, and V3-V6 leads 15 min following 40 mg/ml of intramuscular triamcinolone acetonide (Kenacort-A Retard IM ampule) administration for rashes and itching of her scalp. Troponin was raised (TnI: 0.98 ng/mL), but, on coronary angiography, her coronary arteries were found normal and she recovered with antihistaminic therapy with a final diagnosis of variant type I Kounis syndrome [13]. Additionally, two patients developed anaphylactic shock, with cutaneous and systemic manifestations, following methylprednisolone succinate pulse therapy for neuromyelitis optica and systemic lupus erythematosus [14]. Intradermal skin tests with various types of corticosteroids revealed positive reaction to succinate-containing methyprednisolone, prednisolone, and hydrocortisone in both patients.

Furthermore, another 52-year-old woman with a previous history of allergy to anti-haemorrhoid creams and ointments, developed generalized symmetrical pruritic eruption following intra-articular administration of 1 ml of triamcinolone acetonide. Patch tests were positive to tixocortol pivalate, budesonide, hydrocortisone butyrate, nickel sulfate and potassium dichromate. Intradermal skin prick test was positive to triamcinolone and oral challenge tests were positive to deflazacort and methylprednisolone after 14 and 24 h respectively accompanied by pruritic rash. The diagnosis was allergic contact dermatitis progressing to systemic allergic dermatitis [15].