According to The World Allergy Organization (WAO) Anaphylaxis Committee, anaphylaxis is defined as “a serious systemic hypersensitivity reaction that is usually rapid in onset and may cause death. Severe anaphylaxis is characterized by potentially life-threatening compromise in the airway, breathing and/or the circulation, and may occur without typical skin features or circulatory shock being present”. It is a spectrum of disorders with the severity of symptoms ranging from mild, localized skin reaction to fatal anaphylactic shock resulting cardio respiratory arrest (3). Clinical features can be dermatological manifestation including mucocutaneous involvement, cardiorespiratory, gastrointestinal and symptoms and signs of other organ system involvement (4). Urticarial rash, angioedema causing swelling of the lips, tongue, oropharynx and uvula are the common mucocutaneous manifestation of anaphylaxis. Although mucocutaneous manifestations are the common clinical features, which alone is not enough to diagnose anaphylaxis. In fact skin manifestations can be subtle or absent in 10–20% of cases (4). Respiratory features include stridor, hoarse voice, bronchospasm causing cough or wheezing, prolong expiration, low saturation and cardiovascular features are peripheral vasodilation causing warm peripheries, high volume pulses, arrhythmias, low blood pressure postural hypotension leading to collapse and syncope (severe shock can cause pale, clammy peripheries). Common gastrointestinal (GI) symptoms include nausea, vomiting, abdominal cramps and diarrhea. GI symptoms alone are not diagnostic.
Onset of symptoms and fatal anaphylaxis depends on the type of trigger, dose, route and type of reaction (idiosyncratic vs. dose dependent) (4). Deaths caused by intravenous medications occur most commonly within 5 minutes; Insect stings cause collapse from shock after 10–15 minutes; and fatal anaphylaxis due to food reactions typically cause cardiorespiratory arrest after approximately 30 minutes. Cardiorespiratory arrest more than 4 h after the initial allergen exposure is rare (4).
Ig E-mediated anaphylaxis is considered the classic and most frequent mechanism in which complex immunological cascade is triggered by the interaction of an allergen with the allergen-specific Ig E receptor complex expressed on effector cells, predominantly mast cells and basophils resulting in the release of preformed histamine and other mediators (3). These chemical mediators can result in several pathophysiological changes such as; fluid extravasation leading to airway edema and reduced intravascular volume; vasodilatation leading to distributary shock and reduced effective arterial perfusion; Smooth muscle contraction leading to bronchospasm (and abdominal cramps); direct effect on myocardium leading to myocardial dysfunction and cardiogenic shock. These mechanisms altogether, ultimately can cause tissue hypoxia and hypotension (4).
There are multiple common triggers and most of them are natural substances, but few are synthetic chemicals and medicines. However, most common allergens identified can be categorized into food, drugs and venom (5). In this case presentation, the patient did not have past known allergen. However, he has sprayed sulphur containing herbicide call ‘Gulliver’ (Azimsulfuron) without full protection equipments for about 3 hours that may have led absorption of chemical into circulation via the skin, mucus membrane and respiratory routes resulting in anaphylactic shock. Azimsulfuron is highly soluble in water, semi-volatile and, appears to have potential for leaching to groundwater. Although it has a low mammalian toxicity, it has high potential for bioaccumulation (6). There are no reported cases related to anaphylaxis following spray of Azimsulfuron. However, it is well known fact that a significant proportion of the general population has an allergy to sulphur containing drugs. Figure 1 bellow illustrates 2D structure diagram of Azimsulfuron (6).
Diagnosis of anaphylaxis is clinical and serum tryptase and histamine levels might support the diagnosis retrospectively. The WAO Anaphylaxis Committee has proposed to amend the current NIAID/FAAN criteria to make two simplified criteria as mentioned bellow (3);
Anaphylaxis is highly likely when any one of the following 2 criteria is full field;
1. Acute onset of an illness (minutes to several hours) with simultaneous involvement of the skin, mucosal tissue, or both (e.g., generalized hives, pruritus, flushing, swollen lips-tongue-uvula)
And at least one of the following:
- Respiratory compromise (dyspnea, wheeze-bronchospasm, stridor, reduced PEF, hypoxemia)
- Reduced BP or associated symptoms of end-organ dysfunction (hypotonia [collapse], syncope, incontinence)
- Severe gastrointestinal symptoms (severe crampy abdominal pain, repetitive vomiting), especially after exposure to non-food allergens
2. Acute onset of hypotension or bronchospasm or laryngeal involvement after exposure to a known or highly probable allergen for that patient (minutes to several hours), even in the absence of typical skin involvement.
- Hypotension defined as a decrease in systolic BP greater than 30% from that person's baseline, OR i. Infants and children under 10 years: systolic BP less than (70 mmHg þ [2 x age in years]) ii. Adults and children over 10 years: systolic BP less than <90 mmHg.
- Excluding lower respiratory symptoms triggered by common inhalant allergens or food allergens perceived to cause “inhalational” reactions in the absence of ingestion.
- Laryngeal symptoms include: stridor, vocal changes, odynophagia.
- An allergen is a substance (usually a protein) capable of triggering an immune response that can result in an allergic reaction. Most allergens act through an IgE mediated pathway, but some non-allergen triggers can act independent of IgE (for example, via direct activation of mast cells).
As in this case presentation, with a high degree of suspicion towards the possible trigger, an early diagnosis of anaphylaxis can reduce fatal outcomes. In Sri Lanka, a survey in 2016/2017 revealed 27 percent of the total labour force was engaged in agricultural sectors (7). We emphasize the importance of consideration of allergy and anaphylaxis in similar presentation in an agricultural based country like Sri Lanka.