Couvreur, Céline

Forget, Patrice

Mitchell, John

Thonon, Henri

Cureus

English

Consumption of fava beans in a patient with glucose-6-phosphate dehydrogenase (G6PD) deficiency, also called favism, can lead to a haemolytic crisis. We report the case of a 69-year-old patient of Iranian origin admitted to the emergency department following syncope. The patient's comprehensive interview and blood analysis revealed that the patient presented a haemolytic crisis triggered by fava beans consumption, due to previously undiagnosed G6PD deficiency. The pathophysiology of favism is complex and clinical presentations of G6PD deficiency are numerous due to multiple genetic variants. Indirect signs, such as the presence of methemoglobinaemia and hemighosts on the blood smear, can aid in the diagnosis. This case highlights the importance of considering G6PD deficiency as a potential diagnosis in case of haemolytic crisis, even in elderly patients

DIAL UCLouvain

Syncope in the Emergency Department: A Case Report of a Rare Presentation of Favism.

Aberdeen University Research

Review began 06/18/2024 Review ended 07/05/2024 Published 07/15/2024© Copyright 2024Couvreur et al. This is an open accessarticle distributed under the terms of theCreative Commons Attribution License CC-BY 4.0., which permits unrestricted use,distribution, and reproduction in anymedium, provided the original author andsource are credited.DOI: 10.7759/cureus.64592Syncope in the Emergency Department: A CaseReport of a Rare Presentation of FavismCéline Couvreur , John Mitchell , Patrice Forget , Henri Thonon 1. Emergency Medicine, CHU (Centre Hospitalier Universitaire) UCLouvain (Université Catholique de Louvain) Namur -Godinne, Godinne, BEL 2. Anesthesiology, CHU (Centre Hospitalier Universitaire) UCLouvain (Université Catholique deLouvain) Namur - Godinne, Godinne, BEL 3. Anesthesiology, University of Aberdeen, Aberdeen, GBRCorresponding author: Céline Couvreur, ce.couvreur@student.uclouvain.beAbstractConsumption of fava beans in a patient with glucose-6-phosphate dehydrogenase (G6PD) deficiency, alsocalled favism, can lead to a haemolytic crisis. We report the case of a 69-year-old patient of Iranian originadmitted to the emergency department following syncope. The patient's comprehensive interview and bloodanalysis revealed that the patient presented a haemolytic crisis triggered by fava beans consumption, due topreviously undiagnosed G6PD deficiency. The pathophysiology of favism is complex and clinicalpresentations of G6PD deficiency are numerous due to multiple genetic variants. Indirect signs, such as thepresence of methemoglobinaemia and hemighosts on the blood smear, can aid in the diagnosis. This casehighlights the importance of considering G6PD deficiency as a potential diagnosis in case of haemolyticcrisis, even in elderly patients.Categories: Family/General Practice, Emergency Medicine, HematologyKeywords: haemoglobinemia, hemighosts, syncope, favism, g6pd deficiencyIntroductionGlucose-6-phosphate dehydrogenase (G6PD) is an enzyme involved in the protection of red blood cellsagainst oxidative stresses, the most common being infection [1]. The prevalence of G6PD deficiency isestimated at more than 350 million individuals worldwide [2], with a predominance of males [3]. It is mostcommonly found in Africa, Asia, the Mediterranean basin, and the Middle East.Most patients with G6PD deficiency are asymptomatic but may present with haemolytic crises, particularlywhen eating fava beans. This is why G6PD deficiency is better known as favism. The manifestations of ahaemolytic crisis in patients with favism are diverse, ranging from fatigue to syncope [4].We report the case of a patient admitted to the emergency department following syncope due to ahaemolytic crisis in a context of favism, unaware of having G6PD deficiency. The aim of this article is toreview the different clinical presentations of a haemolytic crisis, as well as diagnostic and therapeuticapproaches.Case PresentationA 69-year-old male of Iranian origin was admitted to the emergency department for syncope. At home, thepatient suffered from loss of consciousness preceded by dizziness, resulting in mild head trauma. Onadmission, the patient reported generalized fatigue and mild abdominal pain for the past 24 hours. Thepatient's history included Brugada syndrome, for which he had an internal defibrillator,hypercholesterolemia and hypertension. His chronic treatment included perindopril and rosuvastatin-ezetimibe. His clinical examination showed blood pressure measurements of 100/60 mmHg, tachycardia at110 beats per minute, temperature at 37.9°C, and pulsed oxygen saturation at 90% on room air. His GlasgowComa Scale (GCS) on admission was 15/15.The patient presented with mucocutaneous jaundice. An analysis of potential arrhythmia recorded in hisdefibrillator was requested and showed no arrhythmia concomitant with the syncope. Arterial blood gaseswere collected on admission and showed arterial oxygen pressure of 73 mmHg and arterial oxygensaturation of 95%. There was therefore a slight discrepancy between the oxygen saturation measured byoximeter and by gasometry. This blood gas analysis also showed a methaemoglobin level of 3% (for a normbelow 2%). Blood biology results are presented in Table 1. Blood smear revealed phantom red blood cellscalled hemighosts (Figure 1).1 2 3 1 Open Access Case ReportHow to cite this articleCouvreur C, Mitchell J, Forget P, et al. (July 15, 2024) Syncope in the Emergency Department: A Case Report of a Rare Presentation of Favism.Cureus 16(7): e64592. DOI 10.7759/cureus.64592Dosage Result Reference RangeC-reactive protein (CRP) 70 mg/L < 5mg/LHaemoglobin 11.1 g/dL 13.3-16.7 g/dLReticulocytes 4.9% 0.5-2%Creatinine 0.7 mg/dL < 1.2 mg/dLTotal bilirubin 6.6 mg/dL < 1.3 mg/dLUnconjugated bilirubin 6.0 mg/dL <0.8 mg/dLLactate dehydrogenase (LDH) 707 U/L < 250 U/LHaptoglobin 0.1 g/L 0.3-2.0 g/LTABLE 1: Patient’s blood biology resultsFIGURE 1: Patient's blood smear with multiple red blood cells partiallyemptied of their contents, called hemighostsThe Coombs test for haemolytic antibodies was negative. Basic bacteriological examination, including chestX-ray, urine sediment and molecular biology test for respiratory viruses, was negative. The patient describedno recent medication changes but did report consumption of fava beans 48 hours prior to admission. Thepatient reported having consumed fava beans several times in the past without developing symptoms andthat he was not known to have G6PD deficiency, in contrast with the current syncope in the context of ahaemolytic crisis due to favism.He was admitted to a general internal medicine unit for monitoring. In the emergency department, given thepresence of haemolytic anaemia with hemighosts, the patient's ethnic origin, and the recent consumption offava beans, a genetic analysis for G6PD deficiency was requested. The results, which came a few days later,showed a partial deficiency. His haemoglobin level dropped to 7.9 g/dL but did not require any red blood celltransfusion; the patient only received an oral folate supplement. After one week, the haemoglobin level was8.5 g/dL and the patient was discharged with recommendations to avoid beans and certain medications.DiscussionG6PD is an enzyme present in every animal cell. It catalyzes the first step of the pentose pathway, one of thefour main pathways of energy metabolism. In a red blood cell, the pentose pathway allows the production ofnicotinamide adenine dinucleotide phosphate (NADPH). NADPH is essential for maintaining glutathione inits reduced form, the only one allowing the red blood cell to defend itself against oxidative stress linked tothe production of free radicals [1]. 2024 Couvreur et al. Cureus 16(7): e64592. DOI 10.7759/cureus.64592 2 of 4Significant oxidative stress can be induced by certain medications, infectious diseases or the consumption ofcertain foods, particularly fava beans. Medications to avoid in patients with favism include primaquine,sulfamethoxazole, nitrofurantoin, and methylene blue. The infectious agents most frequently involved in ahaemolytic crisis are hepatitis A and B viruses, cytomegalovirus, any bacteria responsible for pneumonia,and Salmonella typhi. In addition to fava beans, quinine-based drinks and dietary supplements containingvitamin C are also prohibited [5]. Fava beans contain two beta-glucosides that trigger haemolysis: vicine andconvicine. Once ingested, these two molecules are converted in the intestine, leading to increasedproduction of free radicals. These free radicals are responsible for oxidative stress, increasing glutathioneoxidation and making red blood cells more vulnerable [4].The severity of symptoms is related to the amount of beta-glucosides ingested and depends on the quantityof beans, the type of preparation, the degree of maturity of the beans and patient-specific factors such as age[6,7]. Fresh beans contain more beta-glucosides than dried beans due to their green shell [8]. Soaking beforecooking reduces the vicine and convicine contents by 56% and 34%, respectively. Cooking has little impacton the level of beta-glucosides [9]. These factors explain why the diagnosis of mild to moderate G6PDdeficiency is sometimes made at an advanced age, following a first attack; severe forms being diagnosed inpaediatrics.Genetically, G6PD is an X-linked enzyme, resulting in male predominance. Females can be heterozygoussince they have two copies of the G6PD gene; homozygous forms in populations with a high prevalence arepossible. Due to the genetic mosaicism resulting from X chromosome inactivation, heterozygous femalescan be as deficient in G6PD as males [5]. To date, 217 G6PD genetic variants have been identified andclassified by the World Health Organisation from class I to IV, ranging from the most severe to the mildestforms. Old age is not an exclusion criterion for the diagnosis of favism; mild forms can remain minimallysymptomatic, unlike severe forms discovered in childhood [10]. Patient's ethnic origin is essentialinformation, as these mutations are mainly found in Africa, Asia, the Mediterranean basin, and the MiddleEast [11]. Screening campaigns are organised in high-prevalence regions. Screening is carried out mainly inpatients who have suffered from a first episode of haemolysis and in icteric newborns. The aim of suchscreening is to prevent a major crisis by avoiding high-risk foods or drugs. Rapid testing has becomepossible, particularly in developing countries, thanks to the advent of simpler molecular methods such aspolymerase chain reaction (PCR) [6]. In 2009, Peters et al. also described a correlation between theprevalence of G6PD deficiency and the distribution of malaria, suggesting that G6PD deficiency providesprotection against infection [12].In a patient suffering from favism, symptoms begin between 24 hours and five days after eating fava beans.The main symptoms of a haemolytic crisis or acute haemolytic anaemia are fatigue and abdominal or backpain. A sub-febrile state is sometimes present. To our knowledge, this is the second described case ofsyncope as the inaugural symptom of a haemolytic crisis on favism; the first case having been described bySoyuncu et al. in 2010 [13]. Syncope is defined as a short-duration loss of consciousness, caused by atransient decrease in cerebral blood flow [14]. The hypothesis is that syncope is secondary to a drop incerebral oxygenation caused by a rapid drop in haemoglobin level associated with a state of fever-induceddehydration.Biologically, classic markers of haemolysis are always present: regenerative anaemia, unconjugatedhyperbilirubinemia, low haptoglobin, and increased lactate dehydrogenase (LDH). This hyperbilirubinemiainduces dark urine [6]. Low to moderate methaemoglobinaemia is frequently found chronically in patientswith favism [4]. Methaemoglobin is a form of haemoglobin in which the iron cation is in an oxidized state(ferric rather than ferrous), and therefore unable to transport oxygen. One of the physiological mechanismsfor reducing methaemoglobin to haemoglobin is that of NADPH-dependent methaemoglobin reductase [15].As its name suggests, this enzyme depends on the production of NADPH, which is lacking in G6PD-deficientpatients. In methaemoglobinaemia, as in other haemopathies, a dissociation between pulsed oxygensaturation and arterial oxygen saturation can be observed [16]. In our patient, a slight dissociation wasobserved. During a crisis, microscopic observation of blood cells reveals phantom red blood cells, also called(hemi)ghosts. These are red blood cells partially emptied of their haemoglobin content [17].From a therapeutic point of view, there is little literature on the subject. In most cases of favism, symptomsare moderate and transient, and treatment is symptomatic. Avoidance of the triggering factor andsupporting red blood cell regeneration through oral administration of vitamins B9-12 and iron would be theonly treatment in most cases. In more severe forms, red blood cell transfusions may be necessary. The mostsevere and common complication is acute renal failure. This is the result of acute tubular necrosis due toischemia and tubular obstruction by haemoglobin casts [5] and sometimes requiring dialysis [4]. Fluidrepletion and alkalinisation can prevent haemolysis-induced renal failure [18]. Paracetamol in case of feveris authorized but should not exceed the recommended doses. Cases of severe haemolysis due to paracetamoloverdose have been described [5].ConclusionsHaemolytic crises due to favism may be responsible for atypical presentations such as syncope. The diagnosisis based on patient’s history regarding their ethnic origin and diet, as well as paraclinical examinations 2024 Couvreur et al. Cureus 16(7): e64592. DOI 10.7759/cureus.64592 3 of 4looking for methaemoglobin and hemighosts. This diagnosis must not be forgotten, even in elderly patients.Additional InformationAuthor ContributionsAll authors have reviewed the final version to be published and agreed to be accountable for all aspects of thework.Concept and design:  Céline Couvreur, Patrice Forget, John Mitchell, Henri ThononDrafting of the manuscript:  Céline Couvreur, Henri ThononCritical review of the manuscript for important intellectual content:  Patrice Forget, John Mitchell,Henri ThononSupervision:  Henri ThononDisclosuresHuman subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: Incompliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/servicesinfo: All authors have declared that no financial support was received from any organization for thesubmitted work. Financial relationships: All authors have declared that they have no financialrelationships at present or within the previous three years with any organizations that might have aninterest in the submitted work. Other relationships: All authors have declared that there are no otherrelationships or activities that could appear to have influenced the submitted work.References1. Roper D, Layton M, Rees D, Lambert C, Vulliamy T, De la Salle B, D'Souza C: Laboratory diagnosis of G6PDdeficiency. A British Society for Haematology guideline. Br J Haematol. 2020, 189:24-38. 10.1111/bjh.163662. Testing for G6PD Deficiency for Safe Use of Primaquine in Radical Cure of P. vivax and P. ovale. WorldHealth Organization, Geneva, Switzerland; 2016. https://www.who.int/publications/i/item/WHO-HTM-GMP-2016.9.3. Nkhoma ET, Poole C, Vannappagari V, Hall SA, Beutler E: The global prevalence of glucose-6-phosphatedehydrogenase deficiency: a systematic review and meta-analysis. 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Syncope in the Emergency Department : A Case Report of a Rare Presentation of Favism

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Syncope in the Emergency Department : A Case Report of a Rare Presentation of Favism

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