Background
Iopamidol, a contrast agent widely used internationally, has been considered safe [1], and hypersensitivity reactions following iopamidol administration occur in approximately 1–3% of patients [2, 3]. The most commonly reported adverse reactions include erythema, urticaria, vomiting, and generalized rashes. The most commonly affected organs and systems are the skin, respiratory system, and gastrointestinal tract. Hypersensitivity reactions to iopamidol are acute in 71.1% of cases and are most commonly Class I [4]. Reports of severe and fatal reactions resulting in death are less common [5]. Transient pulmonary and gastric hemorrhage due to iopamidol allergy has never been reported. Here, we report a case of transient pulmonary and gastric hemorrhage following chest and total abdominal enhancement CT with iopamidol in a woman with marginal zone lymphoma who was receiving antineoplastic therapy.
Case presentation
A 60-year-old woman was admitted to our oncology department on 2021-06-21 with recurrent palpitations and findings of anemia for more than 2 months, diagnosed as marginal zone lymphoma and treated with antitumor therapy. Laboratory examinations revealed anemia, renal function damage, hyperuricemia, and chronic viral hepatitis B, and bone marrow puncture results suggested a lymphoma. However, the patient’s platelet count and coagulation, liver, and heart functions were normal, and there was no bleeding. Antinuclear (ANAs), anti-neutrophil cytoplasmic (ANCAs) and anti-glomerular basement membrane (GBM) antibodies were all negative. Complement levels were normal. As part of the examination of her condition, she was required to undergo an enhanced CT examination of the chest and whole abdomen. On the day of the examination, the patient entered the CT room at 10:43 a.m. and an iopamidol syringe was attached without incident. A chest CT was performed at 10:45 a.m. Scattered exudates could be seen (see Fig. 1-ABCD). After a static push of contrast agent, at 10:50 it was shown that the pulmonary exudate was rapidly increasing (see Fig. 1-EFGH). At 10:54, she felt very bloated and had to sit up. At 10:56, She was unconscious after spitting blood. The adjoining room’s emergency physician arrived in the CT room and assisted with resuscitation. Mechanical ventilation was given after endotracheal intubation, and hemorrhagic sputum could be drawn into the airway. An indwelling gastric tube connected to a negative pressure box can induce bloody fluid. At 12:10, the patient became conscious and could move his limbs autonomously. At 14:35, Fibrobronchoscopic alveolar lavage was performed. We saw bloody sputum and several reddish neoplasms in the segmental bronchus. Bronchoscopes at that time used eyepieces, so no photos could be taken. We did not test sputum for the haemosiderin of alveolar macrophages, so Golde score could not be calculated. Despite of the absence of true BAL, we consider an alveolar haemorrhage as probable. She was sent to the ICU for further treatment.
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Fig. 1
(A-D)10:45:45am, before the injection of iopamidol; (E-G)10:50:05am, after the injection of iopamidol; (H)11:30:00am, After endotracheal intubation
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The patient denies a history of food and drug allergies. On physical examination, she had an anemic appearance, and small, 0.5–1 cm, hard, non-tender, and well-defined lymph nodes were palpable in the left axilla and bilateral groins. The remaining superficial lymph nodeswere not palpable. The respiratory sounds in both lungs were slightly coarse, and crackles were heard bilaterally.
The patient was administered levofloxacin for infection, norepinephrine for gastric lavage, esomeprazole for acid inhibition and gastric protection, methylprednisolone sodium succinate for allergy treatment, and.
blood transfusions for improving anemia.(Table 1).
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Table 1
The results of the patient’s blood routine examination
Before CT | After CT | reference range | measuring unit | |
|---|---|---|---|---|
white blood cell, WBC | 7.79 | 14.53\( \uparrow \) | 3.5–9.5 | 10^9/L |
red blood cell, RBC | 2.07\( \downarrow \) | 1.79\( \downarrow \) | 3.8–5.1 | 10^12/L |
Hemoglobin, HGB | 60\( \downarrow \) | 52\( \downarrow \) | 115–150 | g/L |
hematocrit, HCT | 18.7\( \downarrow \) | 16.8\( \downarrow \) | 35–45 | % |
blood platelet | 157 | 177 | 125–350 | 10^9/L |
percentage of neutrophils | 46.5 | 38.6\( \downarrow \) | 40–75 | % |
percentage of lymphocyte | 37.7 | 52.3\( \uparrow \) | 20–50 | % |
percentage of monocyte | 11.5\( \uparrow \) | 6.2 | 3–10 | % |
percentage of eosinophils | 3.7 | 2.2 | 4–8 | % |
percentage of basophils | 0.6 | 0.7 | 0–1 | % |
neutrophils | 3.62 | 5.61 | 1.8–6.3 | 10^9/L |
lymphocyte | 2.94 | 7.6\( \uparrow \) | 1.1–3.2 | 10^9/L |
monocyte | 0.9\( \uparrow \) | 0.9\( \uparrow \) | 0.1–0.6 | 10^9/L |
eosinophils | 0.29 | 0.32 | 0.02-0.52 | 10^9/L |
basophils | 0.05 | 0.1\( \uparrow \) | 0-0.06 | 10^9/L |
On the second day after admission to ICU, gastroscopy showed congestion of the gastric body mucosa, and several mucosal bleeding spots were seen in the greater curvature and posterior wall, without active bleeding or ulceration, and the morphology of mucosal folds was normal, as shown in Fig. 2. Fiberoptic bronchoscopy showed no bleeding, but the patient had a secondary infection after pulmonary hemorrhage. After one week of treatment, the patient was weaned and extubated, and transferred to the general ward.
Fig. 2
Gastroscopy: mucosal congestion in the body of the stomach, several mucosal haemorrhagic spots in the greater curvature and posterior wall, no active bleeding or ulceration, normal pattern of mucosal folds
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Discussion
Pulmonary hemorrhage may be caused by a variety of disorders, and some drugs have also been implicated in the a etiology of diffuse alveolar hemorrhage.On Pneumotox.com site, many publications (see Table 2)are available concerning lung hemorrhage or pulmonary oedema after contrast agents, such as cannabis, abciximab, aspiration, amiodarone, propylthiouracil.
Table 2
Cases of pulmonary hemorrhage from Pneumotox.com (By 2024-3-15)
Article | Drug | background disease | Other drugs/ treatment | Possible reasons of lung haemorrhage |
|---|---|---|---|---|
Uyar 2009 [19] | 5-nitroimidazole | amebiasis | none | PT |
Vizzardi 2008 [20] | abciximab | HP, MI, HF | aspirin, heparin. | CD, HF |
Turan 2020 [21] | abciximab | HP, MI | clopidogrel, aspirin, heparin. | CD |
Seto 2011 [22] | bevacizumab | branch retinal vein occlusion, gastric cancer | none | diminish the regenerative capacity of endothelial cells |
Tahir 2015 [23] | alemtuzumab | RF, Alport syndrome, | renal transplantation, methy prednisolone, chlorpheniramine, paracetamol | Sepsis |
Ohtsuka 1997 [24] | Propylthiouracil | GD | none | AAV |
Yamauchi 2003 [25] | Propylthiouracil | GD, HP, hyperlipidaemia, | Simvastatin, ethy icosapentate, amlodipine besilate | AAV |
El-Fakih 2008 [26] | Propylthiouracil | GD | none | AAV |
Arai 2018 [27] | methimazole | GD | none | AAV |
Perri 2007 [28] | azathioprine | IPF, HP, CKD, bladder cancer | Prednisone, beclomethasone inhalations, nadolol and hydrochlorothiazide | Myelosuppression, thrombocytopenia, pneumonia |
Tanawuttiwat 2010 [29] | Amiodarone | AF, HP, AKI, rhabdomyolysis, | intravenous hydration, metoprolol and warfarin | PT, AHF, MI, CD |
Saeed 2019 [30] | Amiodarone | MI, HF, COPD, AF, T2DM, HP | none | PT |
Mengar 2020 [31] | Cocaine | None(smoking and drinking), | mechanical ventilation, anti-infection | HF |
Villeneuve 2020 [32] | “vaped” electronic Cigarettes(nicotine salt) | none | comprehensive treatment | PT |
Kalinczuk 2011 [33] | Aspirin, clopidogrel | PFO | none | CD |
Kelchen 2013 [34] | aerosol propellant | none | marijuana | PT |
Grassin 2011 [35] | cannabis | none | none | PT |
Moatemri 2016 | cannabis | none | none | PT |
Nakamura 2018 [36] | topikku GX(include acetaminophen and chlorpheniramine) | None | None | CD, PT |
Ugajin 2020 | Iodinated Contrast Medium | CKD, HP, MI, HF | comprehensive treatment | PT, HF, CD* |
The differential diagnosis of pulmonary hemorrhage is broad. Congestive heart failure, infectious causes, vasculitis, thrombocytopenia, coagulation disorders(primary or secondary) should be considered.To our knowledge, this is the first reported case of transient pulmonary and gastric hemorrhage caused by an iopamidol-induced hypersensitivity reaction. Enhanced CT documented the complete pulmonary hemorrhage. The patient furthermore developed hematemesis at the end of the CT examination on sitting up, and lost consciousness. No further bleeding was observed after antiallergic treatment. Based on the patient’s clinical presentation (bleeding developed, resolved quickly, and basophilia) and treatment outcome (the patient recovered after antiallergic treatment), we determined that this was a type I hypersensitivity reaction.
Learning about the physico-chemical and pharmacological properties of drug is the basis of our medicine [6]. Despite the widespread use of iopamidol, the mechanisms underlying its rapid hypersensitivity reactions remain unclear [7]. However, the most commonly accepted view is that non-ionic contrast agents trigger immunoglobulin E (IgE)-mediated allergic reactions [8‐11]. A Type I hypersensitivity reaction is a local or systemic reaction caused by the IgE-mediated release of biologically active mediators from mast cells and basophils, which develops and subsides rapidly. It often causes physiological disturbances with little or no serious tissue or cell damage and has a marked individual and genetic predisposition [12]. We hypothesize that iopamidol acts as a semiantigen that enters the body and acquires immunogenicity by binding to proteins, thereby becoming an allergen. IgE binds to the IgE Fc receptor on the surface of mast cells or basophils via its Fc segment, placing the body in a state of sensitization to iopamidol. This causes capillary dilation and increases vascular permeability, resulting in hemorrhage. Due to limitations of resource constraints or lack of laboratory assays, we couldn’t get more immunological and hypersensitivity tests.
Although studies have shown that skin testing for non-ionic contrast media can help manage immediate hypersensitivity reactions to iodinated contrast media, the specific IgE-mediated mechanisms that may be involved are unclear and are subject to wide variations in positivity rates across national and central study populations, ranging from 4.2–73% [8, 11‐17]. Further, in most cases, the skin test results are negative [18]. The instructions also mention that the iodine allergy test does not predict whether a serious or fatal reaction to the contrast agent will occur; therefore, the iodine allergy test is not recommended. However, taking a detailed history prior to contrast administration and focusing on the patient’s history of allergic reactions may be more accurate than allergy testing in predicting potential adverse reactions.
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Conclusion
We believe that clinicians should ask patients about their allergy history before administering contrast media. Patients with a history of contrast reactions, allergy to iodine, or metabolic or hypersensitivity states have a high incidence of adverse reactions and are advised not to undergo iodine contrast testing unless specifically needed. Detailed history-taking and focusing on a patient’s history of allergic reactions and sensitization may be more accurate than allergy testing in predicting potential adverse reactions. The administration of antihistamines or glucocorticoids as prophylactic medications prior to contrast examination may prevent or reduce the incidence of allergic reactions. Allergic reactions to contrast media can be classified as mild, moderate, or severe. Mild reactions are treated symptomatically, whereas moderate and severe reactions should stop the drug immediately and treated by immediate vascular administration.
Finally, the possibility of adverse reactions needs to be considered, not only among radiologists, but also among other healthcare professionals, such as oncologists, ICU doctors, prescribers, and medical staff, who should be pre-trained in first aid measures and prepared with the necessary resuscitation drugs and equipment. Awareness of the safety of contrast agents must be raised, and it is important to treat hypersensitive individuals with a better understanding of susceptibility risk factors, potential interactions, and other relevant aspects.
Declarations
Ethics approval and consent to participate
Appropriate written informed consent was obtained from the patient for the publication of this case report and accompanying images. This report was approved by the Foshan Hospital of Traditional Chinese Medicine, and the approval number is KY[2023]190.
Consent for publication
Written informed consent was obtained from the patient for publication of this case report and any accompanying images.
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Competing interests
The authors declare no competing interests.
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