Management Strategy for Anaphylaxis in a Patient With Suspected or Confirmed Mastocytosis: A Case Report

Abstract

Patient: Female, 31-year-old

Final Diagnosis: Anaphylaxis

Symptoms: Hypotension

Clinical Procedure: —

Specialty: Anesthesiology • Critical Care Medicine

Objective: Unusual clinical course

Background

Anaphylaxis is a severe, systemic hypersensitivity reaction that poses a potential threat to life. The occurrence of mastocytosis increases the likelihood of severe anaphylactic reactions. Appropriate management is crucial for improving clinical outcomes.

Case Report

The case describes severe anaphylactic shock in a 31-year-old female patient with suspected mastocytosis. The shock occurred following a sting by a hymenopteran insect. The patient required mechanical ventilation and circulatory support for cardio-respiratory failure. Because of insufficient response to intramuscular injections of epinephrine, continuous intravascular infusion was needed. Intensive fluid therapy with balanced crystalloids was administered. As part of supportive treatment, antihistamines (rupatadine via a nasogastric tube) and intravenous glucocorticosteroids were given. Acid-base disturbances were also corrected. The patient was discharged from the intensive care unit on the third day of hospitalization in good general condition.

Conclusions

The core management of anaphylaxis in a patient with suspected or diagnosed mastocytosis is similar to the general recommendations for anaphylaxis treatment. However, it should be noted that patients with mastocytosis can have significantly higher requirements for adrenaline. Continuous intravenous infusion of adrenaline during the first 1 to 2 days following the onset of anaphylaxis may be warranted. Due to the rapid course of anaphylaxis and excessive immune response, more severe disturbances in organ perfusion can occur, resulting in metabolic acidosis. In such patients, intravenous infusion of sodium bicarbonate can be necessary. Therefore, patients with mastocytosis who experience anaphylaxis may be less responsive to epinephrine and should be admitted to the intensive care unit early.

Introduction

Anaphylaxis is a severe, systemic hypersensitivity reaction that poses a potential threat to life [1]. The incidence of anaphylaxis in Europe is estimated at 1.5 to 7.9 cases per 100 000 inhabitants per year, and approximately 8.2 per 100 000 inhabitants annually in Poland. Among patients over the age of 18 years, the most common cause of anaphylaxis in Europe is insect venom, primarily from bees, wasps, and hornets. Other causes include food, such as nuts, wheat, eggs, and cow’s milk, and medications, most commonly antibiotics and analgesics. In most patients, the first symptoms of anaphylaxis typically occur within 30 minutes of exposure to the triggering factor [2,3].

The mechanisms leading to the onset of anaphylaxis can include type I hypersensitivity reactions according to the Coombs classification, cytokine storm-like reactions, complement activation, and mixed reactions [4]. However, the most common pathomechanism is type I hypersensitivity, during which an allergen interacts with an immunoglobulin (Ig) E antibody bound to the high-affinity IgE receptor (FcɛRI) located primarily on mast cells and basophils [5]. Receptor activation leads to the degranulation of a large amount of cytokines and inflammatory mediators from cytoplasmic granules [6,7]. Their effects include dilation of venous and arterial vessels, increased vascular permeability, contraction of smooth muscles in the bronchi and gastrointestinal tract, and activation of the coagulation and fibrinolysis systems, the complement system, and inflammatory cells. They also exert chemotactic effects on eosinophils, thereby prolonging and intensifying the anaphylactic reaction [8].

The risk of developing a severe anaphylactic reaction can vary depending on the type of allergen. In cases of hymenoptera venom allergy (HVA), the most significant risk factors for fatal anaphylactic reactions are middle or advanced age and the coexistence of mast cell activation syndromes (MCAS) [9–11]. MCAS refers to a heterogeneous group of disorders characterized by severe, generalized, and recurrent symptoms resulting from the release of inflammatory mediators from mast cells [12]. MCAS can be classified etiologically as primary, with clonal mast cell proliferation, such as mastocytosis; secondary, triggered by an allergic reaction, most commonly IgE-mediated; or idiopathic [12–14]. The presence of clonal mast cell proliferation increases the likelihood of severe anaphylactic reactions, with the most common trigger being HVA [15–17]. This may be due to the KIT mutations present in most patients with systemic mastocytosis, which amplifies the release of inflammatory mediators during IgE-mediated reactions [18]. The coexistence of HVA and systemic mastocytosis has been reported in up to 28% of cases [19].

The management guidelines recommend intramuscular injections of epinephrine as the first line of treatment. It prevents hypotension, reduces edema, and causes bronchodilatation. Intensive fluid therapy can be necessary, due to systemic vasodilation and capillary leak. Administration of glucocorticoids, antihistamines, and beta-2 agonists can be considered as adjunctive therapy to alleviate swelling, pruritus, and bronchospasm [20]. The patient may develop metabolic acidosis, which is defined as decrease in blood pH less than 7.35 due to reduced bicarbonates levels [1]. The present case report is important because patients with mastocytosis can experience severe hypotensive vasoplegic anaphylaxis and may require continuous intravenous (IV) epinephrine infusion due to persistent anaphylactic shock.

Case Report

A 31-year-old female patient, with no history of chronic illness and no substance use, lost consciousness following a sting by an insect (hornet). Emergency medical services called to the scene noted respiratory distress and significant hypotension. The patient was intubated, and intramuscular injections of 0.5 mg epinephrine and 2 mg clemastine fumarate were administered, along with 8 mg of IV dexamethasone. Immediately after being transported to the emergency department, and following consultation with the on-call anesthesiologist, the patient was admitted to the intensive care unit (ICU) with suspected anaphylactic shock. At the time of ICU admission, the patient was in critical condition and was mechanically ventilated. She had a blood pressure of 51/34 mmHg and a heart rate of 157 beats/min after 6 intramuscular injections of 0.5 mg epinephrine.

During day 1 of ICU admission, hemodynamic parameters were monitored using an advanced hemodynamic monitoring platform. Epinephrine IV was administered via an infusion pump at a maximum dose of 0.25 mcg/kg/min, and intensive fluid therapy with balanced crystalloids was initiated. The patient received 4500 mL of crystalloids, with the first 2 L as a bolus, and the next 2.5 L as a continuous IV therapy. As part of supportive treatment, 28 mg of dexamethasone IV, 2 mg of clemastine fumarate IV, and 20 mg of rupatadine (via a nasogastric tube) was administered. Additionally, owing to metabolic acidosis, 200 mL of sodium bicarbonate 8.4% was given.

During day 2 in the ICU, a decreased requirement for catecholamine support was observed. Pharmacologic sedation was discontinued, and following the return of consciousness and adequate spontaneous breathing, the patient was extubated. The epinephrine infusion was also terminated. The patient received 30 mg of rupatadine orally and 100 mg of hydrocortisone IV. A computed tomography scan of the abdomen was performed. Due to the patient’s report of transient weakness in the right upper limb, a computed tomography scan of the head was also ordered. Imaging and microbiological studies revealed no pathological findings.

On day 3 of hospitalization, the patient was discharged from the ICU in fairly good general condition and transferred to the Department of Allergology and Pulmonary Diseases for further evaluation and treatment. The patient received 20 mg of rupatadine orally (Table 1). Plasma tryptase and lactate levels were also measured during the ICU stay (Table 2).

Table 1.

Medications used in the treatment of anaphylaxis and the consumption during ICU hospitalization.

	Day 1 of ICU admission (12 hours)	Day 2 of ICU admission (24 hours)	Day 3 of ICU admission (36 hours)
Epinephrine	14 mg/12 h Average dose 0.25 mcg/kg/min	20 mg/24 h Average dose 0.18 mcg/kg/min	0
Dexamethasone	28 mg	0	0
Hydrocortisonum	0	100 mg	0
Rupatadine	20 mg	30 mg	20 mg
Sodium bicarbonate	200 mEq	0	0
Clemastine	2 mg	0	0
Balanced crystalloids	4500 mL	1500 mL	500 mL

Table 2.

Plasma tryptase and lactate concentrations measured at selected time points during ICU hospitalization.

Time since onset of first symptoms	1 hour	4 hours	12 hours	24 hours
Tryptase (1–15 μg/L)	>200	78.7	23.4	17.3
Lactate (0.5–2.2 mmol/L)	7.2	10.1	9.3	1

During subsequent hospitalizations in the Department of Allergology and Pulmonary Diseases, further allergological evaluation confirmed a diagnosis of hypersensitivity to hymenoptera venom (Table 3). The diagnosis of mastocytosis was based on bone marrow examination findings in another hospital. The patient was also started on venom immunotherapy. During the first session, dizziness, abdominal pain, and dyspnea was reported; the following sessions were well tolerated by the patient.

Table 3.

Serum immunoglobulin E concentrations for tested allergens in the patient.

IgE sp. I1: Honey bee (SERUM)	5.55 [kU/L]	Reference ranges: IgE sp. class IgE sp. concentration 0 <0.35 1 0.35–0.70 2 0.70–3.5 3 3.5–17.5 4 17.5–50.0 5 50.0–100.0 6 >100.0
IgE sp. I3: Common Wasp (SERUM)	1.01 [kU/L]
IgE sp. I75: Vespa crabro (SUROWICA)	1.58 [kU/L]
IgE sp. I205: Bambus terrestris (bumblebee) (SERUM)	1.45 [kU/L]
IgE sp. I214: rApi m2 Hyaluronidase, Honey bee (SERUM)	0.08 [kU/L]
IgE sp. I215: rApi m3 Acid phosphatase, Honey bee (SERUM)	0.29 [kU/L]
IgE sp. I216: rApi m5 Dipeptidyl peptidase, Honey bee (SERUM)	0.02 [kU/L]
IgE sp. I208: Allergen comp. rApi m 1 (SERUM)	1.78 [kU/L]
IgE sp. I77: European paper wasp venom (SERUM)	0.18 [kU/L]
IgE sp. I209: Allergen comp. rVes v 5 (SERUM)	0.04 [kU/L]
IgE sp. I211: Allergen comp. rVes v 1 (SERUM)	0.1 [kU/L]
IgE sp. I210: Allergent comp. rPol d 5 (SERUM)	0.02 [kU/L]
IgE sp. I217: Allergen comp. rApi m 10 (SERUM)	5.68 [kU/L]

Discussion

The diagnostic criteria for anaphylaxis proposed by the World Allergy Organization in 2020 states that anaphylaxis is likely if there is a sudden onset of symptoms involving the skin and/or mucous membranes, along with at least 1 of the following: hypotension or organ dysfunction; respiratory compromise; or severe gastrointestinal symptoms. Anaphylaxis is also considered likely if, following exposure to a known or highly probable allergen, bronchial obstruction or a sudden drop in blood pressure occurs [19]. In most cases, symptoms involve 2 or more organ systems [21]. The most characteristic symptoms are as follows: (1) symptoms of the skin and mucous membranes, including urticaria, angioedema, flushing, rash, pruritus, erythema, and tearing; (2) respiratory system symptoms, including cough, hoarseness, dysphonia, tachypnea, dyspnea, stridor, bronchospasm, and respiratory arrest; (3) cardiovascular system symptoms, such as chest pain, tachycardia, arrhythmias, hypotension, shock, and cardiac arrest; (4) gastrointestinal system symptoms, such as nausea, vomiting, diarrhea, and abdominal pain; and (5) symptoms of the central nervous system, such as altered mental status, headache, and confusion [20].

Cutaneous symptoms are present in nearly 80% to 90% of patients with anaphylaxis [22]. In our patient, the primary symptom was loss of consciousness, most likely caused by a sudden drop in blood pressure. The clinical presentation thus resembled the typical course of a severe anaphylactic reaction in a patient with systemic mastocytosis. In such patients, cardiovascular symptoms predominate, whereas cutaneous or respiratory symptoms may be absent [23–25]. The differential diagnosis of anaphylaxis should include asthma exacerbation, panic attack, and syncope [19,22,26,27]. The absence of characteristic cutaneous symptoms can significantly complicate diagnosis, and syncope of vasovagal or cardiogenic origin can also present with hypotension. In the described case, the diagnostic process was facilitated by the history of an insect sting shortly before the onset of symptoms.

The therapeutic approach to severe anaphylactic reactions is the same regardless of the presence of abnormal mast cell activation [16,23–25]. Epinephrine is the first-line, life-saving medication [1,8,19,20]. By acting on alpha-1 receptors, it causes vasoconstriction of the peripheral vascular bed, reduces edema, and prevents hypotension. Its action on beta-1 receptors increases myocardial contractility and heart rate. Activation of beta-2 receptors results in bronchodilation and stabilization of mast cells, thereby reducing the release of inflammatory mediators [28]. The greatest benefit is achieved when epinephrine is administered early in the course of treatment. Initial administration is recommended via intramuscular injection into the anterolateral thigh. If intramuscular dosing does not alleviate symptoms, the dose can be repeated, or an IV epinephrine infusion can be considered under hemodynamic monitoring, as was done in the present case [1,8,19,20]. Unfortunately, epinephrine continues to be underutilized in the treatment of anaphylactic shock [29].

Due to fluid extravasation from the intravascular space, the implementation of intensive fluid therapy is also essential. Treatment should begin with a 1-L bolus of crystalloids, followed by continued fluid administration under monitoring of heart rate, blood pressure, and urine output. The patient should be placed in a supine position with elevated lower limbs to counteract distributive shock. It is important to emphasize that attempting to position a patient upright during the onset of anaphylactic shock can trigger empty ventricle syndrome, which significantly increases the risk of sudden cardiac death and results in a lack of response to epinephrine administration [1,4,8,19,21,22]. Providing the patient with an adequately high concentration of oxygen is also crucial. In our patient, mechanical ventilation was monitored through regular arterial blood gas analysis in the ICU.

As adjunctive therapy, the use of glucocorticosteroids, antihistamines, or beta-2 agonists can be considered. Administration of H1-antihistamines can reduce swelling, erythema, and pruritus; however, there is a lack of conclusive evidence supporting their efficacy in the treatment of anaphylaxis [30]. Beta-2 agonists can be useful in the management of bronchospasm but, unlike epinephrine, they do not alleviate respiratory distress caused by upper airway edema. The use of glucocorticosteroids theoretically reduces the symptoms of prolonged anaphylactic reactions and prevents biphasic anaphylaxis; however, their onset of action typically occurs after several hours, and their efficacy in anaphylaxis has never been confirmed by large randomized controlled trials [31]. The administration of adjunctive medications should never delay the use of epinephrine.

A characteristic course of an anaphylactic reaction with prominent cardiovascular involvement raises suspicion of mast cell activation disorders. In the absence of other signs of clonal mast cell disease, apart from anaphylaxis, the decision to proceed with a biopsy, which is necessary for the diagnosis of mastocytosis according to current WHO criteria [32], can pose a challenge for the physician. For this reason, tools have been developed to help identify high-risk patients, such as the REMA score (Spanish Network on Mastocytosis). This tool considers sex, clinical symptoms, and plasma tryptase concentration. In the present case, the REMA score was 3 points (tryptase level >25 ng/mL, +1 point; female sex, +1 point; syncope, +1 point). A score of 2 points or higher indicates an increased likelihood of clonal mast cell disease. The sensitivity of this scoring system is estimated at 92%, and specificity at 81% [15]. An isolated elevation in plasma tryptase concentration should also prompt increased diagnostic vigilance. In a study by Bonadonna et al, 379 patients with systemic anaphylactic reactions were evaluated, and approximately 10% of them were found to have elevated plasma tryptase levels (≥11.4 ng/mL). In most of these patients, bone marrow examination led to the diagnosis of systemic mastocytosis or monoclonal MCAS [33]. For these reasons, in cases similar to the one described here, it appears reasonable to extend diagnostic evaluation to include bone marrow biopsy in order to enable early detection of systemic mastocytosis or MCAS.

The most important element of long-term care for a patient with HVA is the prescription of an emergency kit containing epinephrine. Equally essential is patient education on the correct use of epinephrine and strategies to avoid exposure to potential insect stings. In the present case, the patient was discharged from the Department of Allergology and Pulmonary Diseases with appropriate recommendations and a prescription for an EpiPen. The patient should be referred to an allergy clinic to confirm hypersensitivity to hymenoptera venom. The only treatment modality that can improve quality of life and protect patients from another severe anaphylactic reaction is specific immunotherapy. Every patient without contraindications should undergo a 3- to 5-year course of therapy, which can provide protection in up to 80% to 90% of adult patients [4,19,20].

If MCAS is diagnosed during further evaluation, prophylactic treatment should also be initiated. First-line therapy consists of antihistamines, with doses adjusted individually. As in patients with chronic urticaria, these doses can exceed standard recommendations by up to 4-fold. Oral therapy with high-dose cromones and low-dose glucocorticosteroids can also be used concurrently [23]. In cases of gastrointestinal symptoms, proton pump inhibitors are a consideration. Patients with MCAS should receive specific immunotherapy indefinitely due to the risk of recurrent severe anaphylactic reactions after treatment cessation. In the present case, the patient was assigned to hymenoptera venom immunotherapy. The incidence of adverse events during immunotherapy in patients with MCAS is comparable to that observed in the general population [34].

Conclusions

In summary, anaphylaxis is a relatively rare condition that can lead to patient death. Although overall incidence in the general population is low, patients with mastocytosis are at substantially higher risk of anaphylaxis, particularly following hymenoptera stings. Epinephrine is the primary medication for controlling anaphylactic symptoms, and its prompt administration can significantly increase a patient’s chances of survival. In cases of severe allergic reactions to hymenoptera venom, it is important to consider that the clinical presentation can resemble syncope or a panic attack. Whenever treating a patient in anaphylactic shock following an insect sting, clinicians should assess whether further diagnostic evaluation for mastocytosis is warranted. Routine measurement of plasma tryptase concentration appears to be a reasonable standard for this purpose. Regardless of the presence of mastocytosis, every patient with HVA should receive an epinephrine autoinjector and undergo specific immunotherapy to reduce the risk of recurrent severe anaphylaxis. The core management of anaphylaxis in a patient with suspected or confirmed mastocytosis is similar to general anaphylaxis treatment guidelines. However, it should be noted that patients with mastocytosis can have significantly higher epinephrine requirements. Continuous IV infusion of epinephrine under intensive monitoring can be required in refractory cases or in patients with severe mastocytosis-related anaphylaxis. Due to the rapid course of anaphylaxis and the exaggerated immune response, more severe disturbances in organ perfusion can occur, leading to metabolic acidosis. In such cases, IV infusion of sodium bicarbonate can be necessary when patients are unresponsive to standard resuscitation. Therefore, patients with suspected or confirmed mastocytosis who experience anaphylaxis should be treated in the ICU.