Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic vasculitis that affects small to medium vessels characterised by an eosinophilic-rich and necrotizing granulomatous inflammation [1]. The clinical and laboratory features of the EGPA usually develop in sequential phases (although not always distinguishable):
prodromal or “allergic” phase: it usually occurs in the second and third decades and it is characterised by asthma and chronic rhinosinusitis;
“eosinophilic” phase: characterised by blood eosinophilia and organ eosinophilic infiltrations;
“vasculitic” phase: characterised by clinical symptoms due to a systemic vasculitis of the small to medium vessels (e.g., mononeuritis) [2].
Clinical features typically include asthma, ENT symptoms (such as chronic rhinosinusitis with nasal polyps and otitis media), eosinophilia, multiple and migratory lung infiltrates, peripheral neuropathy, skin lesions (e.g., palpable purpura), myocarditis, pericarditis, gastrointestinal involvement, and systemic manifestations such as fatigue, weight loss, myalgia and arthralgia [3].
There are no diagnostic criteria for EGPA. The 1990 American College of Rheumatology (ACR) criteria and the 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification (ACR–EULAR) criteria should not be used as diagnostic criteria; instead a diagnosis of EGPA should be based on highly suggestive clinical features, objective evidence of vasculitis and ANCA [4, 5].
The incidence of severe perioperative reactions is estimated to be approximately 1 : 7000–10,000 and the aetiology is mainly attributable to neuromuscular blocking agents (NMBAs), antibiotics, natural rubber latex, chlorhexidine, blue dyes, opioids, nonsteroidal anti-inflammatory drugs (NSAIDs) and anaesthetic agents [6, 7].
The pathophysiology of perioperative hypersensitivity (POH) reactions can be subdivided into IgE-mediated and non-IgE-mediated ones; the latter include reactions due to mast cell activation (e.g. mast cell non-specific activation, C and A2-dependent mechanism, MRGPRX2 activation) or to mast cell-independent mechanisms [8]. Although it is normally uncommon, POH following the administration of anaesthetics or other drugs for surgical procedures can be severe and life-threatening.
A 54-year-old woman with chronic rhinosinusitis with nasal polyps (CRSwNP) was scheduled for functional endoscopic sinus surgery (FESS).
Her medical history at the time included Hashimoto thyroiditis controlled with levothyroxine, respiratory distress while taking NSAIDs, gastroesophageal reflux disease (GERD), osteopenia in treatment with 25000 units/month of vitamin D.
The patient underwent general anaesthesia with propofol, sufentanil, remifentanil, rocuronium and then she was treated with cefazolin, paracetamol, pantoprazole and ondansetron. Immediately after the surgery, the woman presented with gastrointestinal pain, dyspnoea, bronchospasm, hypotension and desaturation, so she was promptly treated with 80 mg of methylprednisolone, 10 mg of chlorphenamine and fluids, with a rapid improvement of the symptoms. No skin rash has been described and no blood sample has been taken for tryptase during the reaction.
The woman was subsequently referred to our Center by her general physician and we performed allergy tests for the involved drugs, latex and disinfectants after 6 weeks from the reaction with a negative result, according to the ENDA/EAACI position paper [9]. Then we carried out skin prick tests for common aeroallergens and a patch test for contact allergy with positive results to Dermatophagoides and nickel sulphate. At the general examination no skin lesions were detected; neurological, cardiac and abdominal examinations were normal except pain in the hypogastrium. Thoracic physical examination revealed diffuse wheezing, so we performed a spirometry with bronchoreversibility (salbutamol 400 μg) which documented a reversible obstructive pattern.
The patient also reported that she had lost approximately 8 kg in the last few months. Because of her medical history including CRSwNP, GERD and adult onset asthma, we asked for further examinations (including complete blood count, serum protein electrophoresis, p-ANCA, c-ANCA, ECP, total and specific IgE, thyroid, liver and kidney blood screening exams, ESR, CRP, serum tryptase, a sinus computed tomography, a thorax computed tomography, an echocardiography and an esophago-gastro-duodenoscopy (EGDS) with multiple biopsies).
When she returned, the blood analysis showed a mild absolute-relative eosinophilia (> 10% of leukocytes), negative ANCAs, lung infiltrates and paranasal cavities completely occupied by polyps (despite the recent surgery) were described at lung CT and sinus CT, respectively. The EGDS revealed a massive eosinophilic involvement of the oesophagus, but no macroscopic disease. Echocardiography was normal.
A diagnosis of an ANCA-negative EGPA including CRSwNP, asthma, blood and tissue eosinophilia and lung infiltrates was established. BVAS (Birmingham Vasculitis Activity Score) was 4 and the FFS (Five-Factor Score) was 0.
As the disease activity was low and as the patient had recently undergone steroid therapy, we decided to treat her only with mepolizumab 300 mg s.c. every 28 days.
As there are no diagnostic criteria but only classificatory ones, the diagnosis of EGPA was not straightforward given the atypical clinical presentation.
Melemeni et al. [10] described a similar case of a young (15-year-old) girl with achalasia who suffered from anaphylactic shock after anaesthesia induction during Heller’s esophagomyotomy; however she already had an asthma and a chronic rhinosinusitis (CRS) diagnosis and paediatric EGPA presentation is very rare.
Although several cases of drug-induced EGPA are described in the literature, the patient had already developed this disease; maybe EGPA could therefore have a correlation with a non-allergic hypersensitivity to drugs, but for lack of clinical studies this cannot be stated and more likely the patient developed a perioperative hypersensitivity reaction independent of the underlying disease.
The patient is currently in good health (FFS 0, BVAS 3) and the clinical condition is perfectly controlled with a monthly infusion of mepolizumab 300 mg.
This unusual clinical presentation of EGPA, discovered after a perioperative anaphylaxis, is the second case of Churg-Strauss syndrome in the literature whose diagnosis was formulated starting from a perioperative anaphylaxis, the first in an adult woman.
