SUBMITTED 11 OCT 21 1 REVISION REQ. 14 NOV 21; REVISIONS RECD. 27 DEC 21 2 ACCEPTED 19 JAN 22 3 ONLINE-FIRST: FEBRUARY 2022 4 DOI: https://doi.org/10.18295/squmj.2.2022.017 5 6 Reversible myocarditis following Black widow spider (Latrodectus spp.) bite in 7 Egypt 8 A case report 9 Ahmed G. Emara,1 Abdel-Rhman A. Aboshady,2 *Omar A. Aboshady,3 10 Mohamed M. Shawqi4 11 12 Departments of 1Cardiology, 2Critical Care Medicine Unit and 3Clinical Pharmacology, Faculty 13 of Medicine, Menoufia University, Shebin ElKoum, Egypt; 4Faculty of Medicine, Benha 14 University, Benha, Egypt 15 *Corresponding author’s email: omr.ali@med.menofia.edu.eg 16 17 Abstract 18 Black widow spiders (BWSs) are poisonous spiders of the Arthropoda phylum that live in the 19 Mediterranean region. The effects of BWS bites ranges from local damage to systemic 20 manifestations including paresthesia, stiffness, abdominal cramps, nausea, vomiting, headache, 21 anxiety, hypertension, and tachycardia. However, cardiac involvement following a BWS bite is 22 uncommon. We report a 35-year-old man who developed acute pulmonary edema with 23 electrocardiogram changes that showed ST elevation in leads I, aVL with reciprocal ST segment 24 depression in infero-lateral leads with elevated cardiac biomarkers. Echocardiography showed 25 regional wall motion abnormalities with an impaired ejection fraction of 40%. The condition was 26 reversible after one week of supportive treatment, and the patient was discharged from the hospital 27 with normal electrocardiogram, ejection fraction, and negative cardiac markers. A routine cardiac 28 evaluation, serial ECG, serial cardiac markers, and echocardiography follow-up should be 29 considered for any patient exposed to a BWS bite for detection of any potentially fatal cardiac 30 abnormalities. 31 Keywords: Black widow spider; Egypt; Spider bites; Myocarditis; Heart failure; Kounis 32 syndrome; Acute coronary syndrome. 33 34 Introduction 35 Black widow spiders (BWSs) are a rare but very poisonous species of the Arthropoda phylum that 36 generally live in moderate climatic conditions.1 These spiders are shiny black with a ventral red 37 hourglass mark on females, while males have various dorsal red marks. Their size averages 3-10 38 mm, with females up to 13 mm in length. The spider venom includes a main toxic protein (α-39 latrotoxin) that primarily affects the motor nerve endings, leading to increased catecholamine 40 release and acetylcholine consumption.2 41 42 Patients who have been bitten by a BWS typically complain of various clinical symptoms that 43 range from local to systemic manifestations; a BWS bite can cause soft tissue damage at the site of 44 the bite, with local to generalized pain and/or paresthesia.3,6,7,15,16 In addition, priapism, stiffness, 45 abdominal cramps, nausea, vomiting, headache, tremors, and/or anxiety have been reported.3,5-8 A 46 few patients have hypertension, tachycardia, and/or chest pain.3-6,8,10,16 Only one study has 47 reported acute kidney failure and rhabdomyolysis.1 Myocardial involvement after BWS bites is 48 uncommon, and only a limited number of cases have been recorded with no cases from Egypt.3-5,7-49 10,15,16 Here, we report on a 35-year-old previously healthy man who developed myocarditis 50 complicated by acute heart failure and pulmonary edema following a BWS bite, which is the first 51 case reported from Egypt. 52 53 Case Report 54 A 35-year-old previously healthy man presented to our tertiary hospital 12 hours after having been 55 bitten by a BWS on the lateral aspect of his right leg, 15 cm below the knee joint. After being 56 shown various photos of spiders, the patient chose the photo of the BWS as the attacker spider. 57 Within a few minutes of the bite, he developed local severe burning pain that rapidly involved all 58 of his thigh. Fifteen minutes later, he became nauseous with severe diffuse abdominal pain, back 59 pain, dizziness, headache, and severe muscle cramping in his lower limbs. On examination, he had 60 priapism and generalized tremors. 61 62 On admission, he was noted to appear anxious and diaphoretic. His vital signs were as follow: 63 blood pressure 150/100 mmHg, pulse rate 110/min, respiratory rate 40 /min, oxygen saturation 64 98%, and temperature 37.3°C. Physical examination revealed a 3 x 2 mm area of erythema at the 65 bite site, board-like abdominal rigidity, and hyperactive stretch reflexes. Cardiac examination 66 revealed rapid S1 and S2 with S3, and no murmur or rub. Other than a slight leukocytosis (total 67 leucocyte count was 15×103; normal range 4-10×103) with mild elevation in the absolute 68 eosinophilic count (0.9×103/L; normal range 0.0-0.4×103/L), laboratory findings and arterial blood 69 gases were normal. 70 71 The patient was given tetanus prophylaxis with intravenous analgesics, hydrocortisone, anti-72 histamine (pheniramine maleate 22.75 mg/day), and fluids (Ringer’s lactate 1.5 L/day). Anti-73 venom was not given because it is unavailable in Egypt. 74 75 Four hours later, the patient developed progressive dyspnea, orthopnea, and retrosternal chest 76 pain. An electrocardiogram was obtained that showed an ST-segment elevation of 0.5 mm in leads 77 I, and aVL with reciprocal ST-segment depression in leads II, III, aVF, and V2-V6 (Figure 1). 78 Cardiac biomarkers were CK-MB 89.9 IU/L (0-25 IU/L) and cTnI 5.1 ng/ml (0-0.6 ng/ml). A 79 chest radiograph showed exaggerated pulmonary vascular markings consistent with pulmonary 80 edema. Echocardiography, done 17 hours of his presentation, revealed impaired left ventricular 81 systolic function, with an ejection fraction of 42%. There were regional wall motion 82 abnormalities, including hypokinesis of the mid-basal anterior, mid-basal posteroseptal, mid-83 lateral, and basal inferior walls, with preserved thickness. In addition, the pericardium was noted 84 to be thickened, with a rim of pericardial effusion on the lateral wall (Figure 2). 85 86 The patient was admitted to the intensive care unit and was treated with intravenous furosemide 20 87 mg/8 h, nitroglycerine infusion, intravenous morphine, captopril 12.5 mg/8 h, and prophylactic 88 enoxaparin 80 IU/24 h. Later, beta-blocker (bisoprolol 2.5 mg/24 h for 1 month) was added to 89 maintain a heart rate of 60-70 bpm and good coronary perfusion. 90 91 The dyspnea improved rapidly after this supportive therapy. The pain, headache, dizziness, 92 tremors and muscle cramps disappeared after 48 hours. However, hyperreflexia and priapism 93 continued to the fourth day. The patient’s cardiac enzymes, electrocardiogram and echo findings 94 are shown in Table 1. He was discharged on the sixth day with resolution of his symptoms. At that 95 point, his electrocardiogram had normalized and the ejection fraction was estimated to be 51% on 96 repeated echocardiography. 97 98 Informed written consent for publication of this case report and figures was obtained from the 99 patient. 100 101 Discussion 102 Our patient had developed the commonly reported symptoms of latrodectism, such as nausea, 103 pain, muscle rigidity, headache, tremors, and muscle cramping.3,5-8,15,16 In addition, a moderate 104 degree of priapism was reported, which is also recorded in the literature.3 The hypertension and 105 tachypnea that our patient developed were similar to previous studies.4,5,8,16 106 107 Cardiac involvement following a BWS bite is uncommon. Only a few cases have been reported in 108 the literature, with effects ranging from reversible myocarditis to acute severe fulminant heart 109 failure and cardiogenic shock.1,4,5,7-10 Table 2 summarizes the available reported cases with cardiac 110 involvement after BWS bites in the literature. Most cases have been reported in males, and most 111 of them had myocarditis after BWS bite.3-5,7-10,15,16 The majority of cases presented with chest pain 112 or other manifestations suggesting pulmonary edema or heart failure.3-5,7-10,15,16 Eight cases 113 showed elevated levels of cardiac biomarkers.4,5,7-10,15,16 Only a few cases showed ST segment 114 changes that were similar to our findings.7-10,16 Cardiac dysrhythmia, such as atrial fibrillation and 115 incomplete bundle branch block, have also been reported.7,8 116 117 Although the underlying mechanism of cardiac affection after a BWS bite is still not fully 118 understood, there are many possible explanations, such as the direct toxic effect of α-latrotoxin on 119 cardiomyocytes producing a form of toxic myopericarditis.5,7-10 Recently, the hyperadrenergic 120 state was claimed to primarily be involved (broken heart syndrome).4 In addition, α-latrotoxin, 121 which is a foreign protein, might induce an allergic reaction producing a form of hypersensitivity 122 myopericarditis.1 α-latrotoxin also induces inflammatory mediator release, which could induce 123 coronary artery spasm (Kounis syndrome).1 124 125 From these proposed mechanisms of cardiac affection, the heart can be affected by two main 126 pathologies: myopericarditis and/or coronary artery spasm. However, the clinical presentation 127 depends on which of the two pathologies predominates. When coronary artery spasm is the 128 dominant pathology, the main presentation is typically chest pain or even acute coronary 129 syndrome. When myopericarditis predominates, however, the main presentation is heart failure 130 and pulmonary edema. In echocardiography, hypersensitivity myopericarditis usually shows 131 heterogeneous segmental wall motion abnormalities. In contrast, coronary artery spasm shows 132 segmental wall motion abnormalities in certain territory. Late gadolinium enhancement in cardiac 133 magnetic resonance shows patchy sub-epicardial distribution which is not consistent with any 134 coronary territory. Distribution in coronary artery spasm, however, is usually in the sub-135 endocardial and consistent with the infract-related artery. In our case, we suspect the pathology 136 was mostly combined, with greater spasm, which was reflected in the electrocardiogram. 137 138 Treatment of the BWS bites depends mainly on the severity of presentation.11 Most of cases are 139 mild and only require oral pain medication and tetanus prophylaxis. In severe cases, however, 140 parental opioids or/and benzodiazepines might be required.11 Antivenom administration is 141 reported to reduce pain duration to less than 24 hours in approximately 80% of cases; it is reported 142 to reduce severity, with home discharge in 90% of patients.11-13 However, allergic reactions, serum 143 sickness, and rare reports of fatalities have been reported from antivenom administration.11,13,14 144 Unfortunately, given that BWS bites are rare in Egypt, we did not have antivenom in our center. 145 146 Conclusion 147 To the best of our knowledge, this case is the first to be reported from Egypt and to present with 148 electrocardiogram changes typical of acute myocardial infarction in the literature. From this case, 149 clinicians should be aware that reversible myocarditis can occur after a BWS bite. Moreover, it is 150 recommended that a complete cardiac evaluation be performed for every case of BWS bite to 151 screen for myopericarditis and coronary artery spasm. 152 153 Authors’ Contribution 154 AGE and AAA managed the case clinically. All authors contributed equally to literature review, 155 drafting, and critically revising the final version of the paper. 156 157 References 158 1. Bshabshe A A, Alfaifi M, Alsayed AF. Black widow spider bites experience from tertiary care 159 center in Saudi Arabia. Avicenna J Med 2017; 7:51. doi: 10.4103/2231-0770.203606. 160 2. Ushkaryov Y A, Volynski K E, Ashton A C. The multiple actions of black widow spider toxins 161 and their selective use in neurosecretion studies. Toxicon 2004; 43:527–42. doi: 162 10.1016/J.TOXICON.2004.02.008. 163 3. Bucur I J, Obasi O E. Spider bite envenomation in Al Baha Region, Saudi Arabia. Ann Saudi 164 Med 1999; 19:15–9. doi: 10.5144/0256-4947.1999.15. 165 4. Dendane T, Abidi K, Madani N, Benthami A, Gueddari FZ, Abouqal R, et al. Reversible 166 myocarditis after black widow spider envenomation. Case Rep Med 2012; 2012:4–7. doi: 167 10.1155/2012/794540. 168 5. Erdur B, Turkcuer I, Bukiran A, Kuru O, Varol I. Uncommon cardiovascular manifestations 169 after a Latrodectus bite. Am J Emerg Med 2007; 25:232–5. doi: 10.1016/J.AJEM.2006.11.005. 170 6. Kara H, Ak A, Bayir A, Avci A. Case Report: Reversible myocarditis after spider bite. BMJ 171 Case Rep 2013; 2013. doi: 10.1136/BCR-2013-008957 172 7. Levine M, Canning J, Chase R, Ruha A-M. Cardiomyopathy following Latrodectus 173 envenomation. West J Emerg Med 2010; 11:521. 174 8. Pneumatikos I A, Galiatsou E, Goe D, Kitsakos A, Nakos G, Vougiouklakis T G. Acute fatal 175 toxic myocarditis after black widow spider envenomation. Ann Emerg Med 2003; 41:158. doi: 176 10.1067/MEM.2003.32. 177 9. Pulignano G, Del Sindaco D, Giovannini M, Zeisa P, Faia M, Soccorsi M, et al. Myocardial 178 damage after spider bite (Latrodectus tredecimguttatus) in a 16-year-old patient. G Ital Cardiol 179 1998; 28:1149–1153. 180 10. Sari I, Zengin S, Davutoglu V, Yildirim C, Gunay N. Myocarditis after black widow spider 181 envenomation. Am J Emerg Med 2008; 26:630. doi: 10.1016/j.ajem.2007.09.012. 182 11. Clark R F, Wethern-Kestner S, Vance M V, Gerkin R. Clinical presentation and treatment of 183 black widow spider envenomation: a review of 163 cases. Ann Emerg Med 1992; 21:782–7. doi: 184 10.1016/S0196-0644(05)81021-2. 185 12. Ellis R M, Sprivulis P C, Jelinek G A, Banham N D G, Wood S V, Wilkes G J, et al. A 186 double-blind, randomized trial of intravenous versus intramuscular antivenom for red-back spider 187 envenoming. Emerg Med Australas 2005; 17:152–6. doi: 10.1111/J.1742-6723.2005.00720.X. 188 13. Isbister G K, Brown S G A, Miller M, Tankel A, Macdonald E, Stokes B, et al. A randomised 189 controlled trial of intramuscular vs. intravenous antivenom for latrodectism--the RAVE study. 190 QJM 2008; 101:557–65. doi: 10.1093/QJMED/HCN048. 191 14. Murphy C M, Hong J J, Beuhler M C. Anaphylaxis with Latrodectus antivenin resulting in 192 cardiac arrest. J Med Toxicol 2011; 7:317–21. doi: 10.1007/S13181-011-0183-1. 193 15. Piscopo A, Massari F, Scicchitano P, Sanasi M, De Palo M, Caldarola P, et al. Acute 194 myocarditis after black widow spider bite: a case report. Cardiol Ther 2020; 9:569–75. doi: 195 10.1007/s40119-020-00178-3. 196 16. Yaman M, Mete T, Ozer I, Yaman E, Beton O. Reversible myocarditis and pericarditis after 197 black widow spider bite or kounis syndrome? Case Rep Cardiol 2015; 2015. doi: 198 10.1155/2015/768089. 199 200 Table 1: ECG, cardiac enzymes, and ejection fraction findings over the admission period and one 201 week after discharge 202 ECG Cardiac enzymes Ejection fraction CK-MB (0 - 25IU/L) cTnI (0 - 0.6 ng/ml) Four hours after admission ST-segment elevation (0.2 mv) in leads I, aVL with reciprocal depression (0.3 mv) in II, III, aVF and V2-V6 89.9 IU/L 5.1 ng/ml 42% Ten hours after admission ST-segment elevation (0.1 mv) in leads I, aVL with reciprocal depression (0.2 mv) in II, III, aVF and V2-V6 79.08 IU/L Not done Not done One day after admission ST-segment elevation (0.1mv)in leads I, aVLwith reciprocal depression (0.2 mv) in II, III, aVF and V2-V6 24.07 IU/L 3.2 ng/ml 43% Two days after admission Normal 6.5 IU/L 0.5 ng/ml 51% One week after discharge Normal 6.1 IU/L 0.5 ng/ml 56% 203 Table 2: Available reported cases with cardiac involvement after BWS bites in literature. 204 Year Age/sex Cardiac presentation ECG Echocardiography Cardiac markers Diagnosis Piscopo et al., 202015 50/M Not mentioned - Diphasic T wave in the lateral leads at admission. - At day 3, ECG showed sinus rhythm and negative T wave in the lateral and inferior leads. -Abnormalities in left ventricular wall motions and moderate systolic dysfunction (hypokinesia of LV middle/ basal segment of inferior, lateral and inferior-lateral wall. -LVEF= 48% Positive Acute myocarditis Yaman et al., 201516 15/M Pulmonary edema/ heart failure - ST depression in II, III, aVF, aVL and V3-V6 - EF=22% - Global hypokinesia - Rim of pericardial effusion Positive Reversible myopericarditis Bucur et al., 20124 35/M Pulmonary edema/ heart failure - Sinus tachycardia - Hyperacute T in V3-V6 - EF= 48% - Septal and lateral wall hypokinesia Positive Reversible myopericarditis Levine et al., 20107 22/M Pulmonary edema - Incomplete right bundle branch block - ST uptake in V1- V6 - EF= 35% - Mild to moderate tricuspid regurg Positive Reversible myopericarditis Sari et al., 200810 65/M Chest pain - ST elevation in II and aVF - Hyperacute T in V3-V6 - Normal Positive Kounis syndrome Erdur et al., 20075 22/M Chest pain, severe hypertension - Inverted P in leads II, III, aVF, aVL and V1 - EF = 40% - Anteroseptal wall hypokinesia Positive Reversible toxic myocarditis Pneumatikos et al., 20038 19/F Cardiogenic shock - Atrial fibrillation - Incomplete right bundle branch block - EF = 20 % - Global hypokinesia Positive Acute fatal toxic myocarditis Bucur et al., June 1988 to May 19973 Seven cases (13-57 years) Ranging from chest pain to pulmonary edema - Not mentioned - Not mentioned Not mentioned All cardiac events were reversible Pulignano et al., 19989 16/M Typical chest pain - ST-T changes in precordial leads - Akinesia of interventricular septum - Depressed left ventricular function Positive Reversible toxic myocarditis 205 206 207 Figure 1: Initial electrocardiogram showing ST-segment elevation in leads I, aVL, and ST-208 segment depression in leads II, III, aVF, and V2–V6. 209 210 211 A B 212 Figure 2: (A) Echocardiography showing normal left ventricular end-diastolic diameter and 213 impaired left ventricular systolic function with an ejection fraction (EF) of 42%. (B) 214 Echocardiography showing thickening of the pericardium with rim of pericardial effusion on 215 lateral wall and right atrium. 216 217