Hypersensitivity Myocarditis Research Articles

Hypersensitivity myocarditis induced by isoniazid overdose in a 15-year-old girl: a case report.

Myocarditis represents a diverse group of inflammatory diseases affecting the heart muscle, with both infectious and non-infectious etiologies. Among the non-infectious causes, drug-induced hypersensitivity reactions are rare but serious. Isoniazid, a cornerstone in tuberculosis treatment, is known for its hepatotoxicity but has rarely been documented to cause hypersensitivity myocarditis. We present a case of a 15-year-old girl from Eastern Turkmenistan who was admitted to our emergency department with altered consciousness and seizure activity. She was diagnosed with status epilepticus and treated accordingly. The patient, with no prior medical history, was found to have hypotensive shock and myocarditis upon further examination. A detailed history revealed she had ingested 45 tablets of expired isoniazid in a suicide attempt. She was treated with pyridoxine and supportive therapies, resulting in a gradual recovery. This case underscores the critical need to consider drug-induced hypersensitivity myocarditis in the differential diagnosis of myocarditis, especially in patients with recent medication use. Prompt recognition and appropriate treatment with pyridoxine, steroid, and supportive cardiac care can be lifesaving. This case also highlights the importance of awareness regarding the potential cardiotoxic effects of isoniazid overdose.

Is Acute Clozapine-Induced Hypersensitivity Myocarditis Over-Diagnosed in Australia?

Is Acute Clozapine-Induced Hypersensitivity Myocarditis Over-Diagnosed in Australia?

Immunomodulating and Immunosuppressive Therapy for Virus-Negative Immune-Mediated Myocarditis.

Myocarditis is an inflammatory disease of the myocardium caused by infectious and noninfectious agents. Clinical manifestations range from mildly symptomatic forms to acute heart failure, cardiogenic shock, life-threatening arrhythmias and sudden death. Myocarditis is still a challenging diagnosis because of its wide variability in clinical presentation and unpredictable course. Moreover, a standardized, specific treatment in not yet available. Immunosuppressive treatment for virus-negative lymphocytic myocarditis is still controversial. Conversely, immunosuppression is well established in sarcoidosis, eosinophilic, giant-cell, drug hypersensitivity, and trauma-related myocarditis as well as lymphocytic myocarditis associated with connective tissue diseases or with the rejection of a transplanted heart. Recently, immunosuppressive therapy has been also recognized as an effective treatment in virus-negative inflammatory cardiomyopathy. The aim of this review is to underline the role of immunomodulating and immunosuppressive therapies in patients with immune-mediated myocarditis and illustrate the different treatment strategies depending on the etiology. An endomyocardial biopsy remains the gold standard for the diagnosis of myocarditis as well as for a tailored treatment.

Cardiovascular Events After Coronavirus Disease 2019 Vaccinations: Hypersensitivity Myocarditis After Coronavirus Disease 2019 Vaccines, Diagnostic and Long-term Considerations.

Cardiovascular Events After Coronavirus Disease 2019 Vaccinations: Hypersensitivity Myocarditis After Coronavirus Disease 2019 Vaccines, Diagnostic and Long-term Considerations.

Reply to Letter to the Editor: 'Cardiovascular Events After Coronavirus Disease 2019 Vaccinations: Hypersensitivity Myocarditis After Coronavirus Disease 2019 Vaccines, Diagnostic and Long-term Considerations'.

Reply to Letter to the Editor: 'Cardiovascular Events After Coronavirus Disease 2019 Vaccinations: Hypersensitivity Myocarditis After Coronavirus Disease 2019 Vaccines, Diagnostic and Long-term Considerations'.

Myocarditis Related-COVID-19 mRNA Vaccination: A Narrative Review

The unprecedented impact of the coronavirus disease-19 (COVID-19) pandemic on society and the global economy has highlighted the urgent need for an effective and safe vaccine. One of the very rare side effects of this vaccine is myocarditis, which was realized to be a terrible complication of the COVID-19 mRNA vaccine. A recent study showed an increase in 1824 events of myocarditis reported to VAERS, 383 (21.00%) reported after receiving a single dose of vaccine, then 956 (52.41%) after injection of the second dose. The most common complaint is chest pain that appears within 1 week after the injection. Young and male patients have a high incidence. The pathophysiology of post-mRNA vaccination myocarditis remains unclear, with one study hypothesizing it to be due to hypersensitivity myocarditis and another study suggesting another possible mechanism is molecular mimicry. The main aim of this literature review is to improve knowledge, prevention, and management, as well as determine the incidence between the COVID-19 mRNA vaccine and myocarditis.

Cytokinopathy with aberrant cytotoxic lymphocytes and profibrotic myeloid response in SARS-CoV-2 mRNA vaccine-associated myocarditis.

Rare immune-mediated cardiac tissue inflammation can occur after vaccination, including after SARS-CoV-2 mRNA vaccines. However, the underlying immune cellular and molecular mechanisms driving this pathology remain poorly understood. Here, we investigated a cohort of patients who developed myocarditis and/or pericarditis with elevated troponin, B-type natriuretic peptide, and C-reactive protein levels as well as cardiac imaging abnormalities shortly after SARS-CoV-2 mRNA vaccination. Contrary to early hypotheses, patients did not demonstrate features of hypersensitivity myocarditis, nor did they have exaggerated SARS-CoV-2-specific or neutralizing antibody responses consistent with a hyperimmune humoral mechanism. We additionally found no evidence of cardiac-targeted autoantibodies. Instead, unbiased systematic immune serum profiling revealed elevations in circulating interleukins (IL-1β, IL-1RA, and IL-15), chemokines (CCL4, CXCL1, and CXCL10), and matrix metalloproteases (MMP1, MMP8, MMP9, and TIMP1). Subsequent deep immune profiling using single-cell RNA and repertoire sequencing of peripheral blood mononuclear cells during acute disease revealed expansion of activated CXCR3+ cytotoxic T cells and NK cells, both phenotypically resembling cytokine-driven killer cells. In addition, patients displayed signatures of inflammatory and profibrotic CCR2+ CD163+ monocytes, coupled with elevated serum-soluble CD163, that may be linked to the late gadolinium enhancement on cardiac MRI, which can persist for months after vaccination. Together, our results demonstrate up-regulation in inflammatory cytokines and corresponding lymphocytes with tissue-damaging capabilities, suggesting a cytokine-dependent pathology, which may further be accompanied by myeloid cell-associated cardiac fibrosis. These findings likely rule out some previously proposed mechanisms of mRNA vaccine--associated myopericarditis and point to new ones with relevance to vaccine development and clinical care.

The discrepancies between clinical and histopathological diagnoses of cardiomyopathies in patients with stage D heart failure undergoing heart transplantation.

BackgroundThis study aimed to determine the etiology of stage-D heart failure (HF) and the prevalence and prognosis of misdiagnosed cardiomyopathy in patients undergoing heart transplantation.Methods and resultsWe retrospectively reviewed 127 consecutive patients (mean age, 42 years; 90 [71%], male) from February 1994 to September 2021 admitted for heart transplant in our tertiary center. Pre-transplant clinical diagnosis was compared with post-transplant pathological diagnosis. The most common misdiagnosed cardiomyopathy was nonischemic cardiomyopathy accounting for 6% (n = 8) of all patients. Histopathological examination of explanted hearts in misdiagnosed patients revealed 2 arrhythmogenic cardiomyopathy, 2 sarcoidosis, 1 hypertrophic cardiomyopathy, 1 hypersensitivity myocarditis, 1 noncompacted cardiomyopathy, and 1 ischemic cardiomyopathy. Pre-transplant cardiac MRI and endomyocardial biopsy (EMB) were performed in 33 (26%) and 6 (5%) patients, respectively, with both performed in 3 (3% of patients). None of the patients undergoing both cardiac tests were misdiagnosed. During the 5-years follow-up period, 2 (25%) and 44 (37%) patients with and without pretransplant misdiagnosed cardiomyopathy died. There was no difference in survival rate between the groups (hazard ratio: 0.52; 95% CI:0.11–2.93; P = 0.314).ConclusionsThe prevalence of misdiagnosed cardiomyopathy was 6% of patients with stage-D HF undergoing heart transplantation, the misdiagnosis mostly occurred in nonischemic/dilated cardiomyopathy. An accurate diagnosis of newly detected cardiomyopathy gives an opportunity for potentially reversing cardiomyopathy, including sarcoidosis or myocarditis. This strategy may minimize the need for advanced HF therapy or heart transplantation. With advances in cardiac imaging, improvements in diagnostic accuracy of the etiology of HF can improve targeting of treatment.

Ten questions about eosinophilic myocarditis

Eosinophilic myocarditis is a rare form of myocardial inflammation characterized by interstitial infiltration by eosinophils. Clinical presentation may vary from complete absence of symptoms to fulminant myocarditis with cardiogenic shock, to chronic heart failure due to progression to restrictive cardiomyopathy. The main causes of eosinophilic myocarditis are hypersensitivity reactions secondary to drug exposure, eosinophilic granulomatosis with polyangiitis, hypereosinophilic syndrome and infections. Antibiotics and agents acting on the central nervous system are the most frequently reported drugs capable of causing hypersensitivity myocarditis. Infections are usually due to intestinal parasites. Imaging techniques together with clinical and laboratory data help rising the suspicion of eosinophilic myocarditis. However, the definite diagnosis is made by endomyocardial biopsy. The evidence of eosinophilic infiltrate among myocytes allows to start an immunosuppressive treatment, usually based on corticosteroids, that are the cardinal therapy for eosinophilic myocarditis. Anticoagulation should be undertaken in case of endoventricular thrombosis, which frequently complicates eosinophilic myocarditis, mainly those cases associated with hypereosinophilic syndrome and eosinophilic granulomatosis with polyangiitis. In this focused review, we will try to provide answers to the most common questions on the causes, presentation, diagnosis, treatment, and outcomes of eosinophilic myocarditis.

Pancarditis as the Clinical Presentation of Eosinophilic Granulomatosis with Polyangiitis: A Multimodality Approach to Diagnosis

Eosinophilic pancarditis (EP) is a rare, often unrecognized condition caused by endomyocardial infiltration of eosinophil granulocytes (referred as eosinophilic myocarditis, EM) associated with pericardial involvement. EM has a variable clinical presentation, ranging from asymptomatic cases to acute cardiogenic shock requiring mechanical circulatory support (MCS) or chronic restrictive cardiomyopathy at high risk of progression to dilated cardiomyopathy (DCM). EP is associated with high in-hospital mortality, particularly when associated to endomyocardial thrombosis, coronary arteries vasculitis or severe left ventricular systolic dysfunction. To date, there is a lack of consensus about the optimal diagnostic algorithm and clinical management of patients with biopsy-proven EP. The differential diagnosis includes hypersensitivity myocarditis, eosinophil granulomatosis with polyangiitis (EGPA), hypereosinophilic syndrome, parasitic infections, pregnancy-related hypereosinophilia, malignancies, drug overdose (particularly clozapine) and Omenn syndrome (OMIM 603554). To our knowledge, we report the first case of pancarditis associated to eosinophilic granulomatosis with polyangiitis (EGPA) with negative anti-neutrophil cytoplasmic antibodies (ANCA). Treatment with steroids and azathioprine was promptly started. Six months later, the patient developed a relapse: treatment with subcutaneous mepolizumab was added on the top of standard therapy, with prompt disease activity remission. This case highlights the role of a multimodality approach for the diagnosis of cardiac involvement associated to systemic immune disorders.

Cardiac MRI in Suspected Acute Myocarditis After COVID-19 mRNA Vaccination.

To evaluate cardiac MRI characteristics in patients with suspected hypersensitivity myocarditis following mRNA COVID-19 vaccination. Patients clinically suspected of acute myocarditis after COVID-19 vaccination were retrospectively analyzed and compared against a healthy control group. Cardiac MRI protocol included parameters such as T1 and T2 relaxation times, extracellular volume (ECV), T2 signal intensity ratio, and late gadolinium enhancement (LGE). Lymph node size was assessed in the patient group on the injection side. Student t-test, analyses of variance (ANOVA) with Tukey post-hoc test, and χ2 test were used for statistical analysis. 20 patients with clinically suspected post-vaccine myocarditis (28 ± 12 years; 12 men) and 40 controls (31 ± 11years; 25 men) were evaluated. According to the 2018 Lake Louise criteria (LLC), patients with clinically suspected myocarditis were further subdivided into an LLC-positive group (n = 9) and an LLC-negative group (n = 11). The mean time of symptom onset after vaccination was 1.1 ± 1.2 days (LLC-positive) and 6.5 ± 9.2 days (LLC-negative). Group differences in inflammatory variables between myocarditis patients and control subjects were more pronounced in the LLC-positive group (e. g., T1 relaxation time: 1041 ± 61 ms [LLC positive] vs. 1008 ± 79 ms [LLC-negative] vs. 970 ± 25 ms [control]; p <.001; or T2 signal intensity ratio 2.0 ± 0.3 vs. 1.6 ± 0.3 [LLC-negative] and vs. 1.6 ± 0.3 [control], p = .012). LLC-positive patients were significantly faster in receiving an MRI after initial symptom onset (8.8 ± 6.1 days vs. 52.7 ± 33.4 days; p = .001) and had higher troponin T levels (3938 ± 5850 ng/l vs. 9 ± 11 ng/l; p <.001). LGE lesions were predominantly located at the subepicardium of the lateral wall. Axillary lymphadenopathy was more frequent in the LLC-positive group compared to the LLC-negative group (8/9 [89 %] vs. 0/11 [0 %], p < 0.001). Vaccine-induced myocarditis should be considered in patients with acute symptom onset after mRNA vaccination, especially if elevated serum troponin T is observed. Imaging findings of vaccine-induced myocarditis are similar to virus-induced myocarditis, allowing for the use of the Lake Louise Criteria for diagnostic purposes. · Vaccine-induced hypersensitivity myocarditis can be confirmed with cardiac MRI. · Especially patients with sudden onset of symptoms and elevated serum troponin T had positive cardiac MRI findings. · Cardiac MRI characteristics of vaccine-induced myocarditis are similar to those in virus-induced myocarditis. · Kravchenko D, Isaak A, Mesropyan N et al. Cardiac MRI in Suspected Acute Myocarditis After COVID-19 mRNA Vaccination. Fortschr Röntgenstr 2022; 194: 1003 - 1011.

Reply to 'Letter to the Editor: Acute hypersensitivity myocardial infarction (Kounis syndrome) and hypersensitivity myocarditis following COVID-19 vaccine vaccination'.

Reply to 'Letter to the Editor: Acute hypersensitivity myocardial infarction (Kounis syndrome) and hypersensitivity myocarditis following COVID-19 vaccine vaccination'.

Rare acute hypersensitivity myocardial infarction (Kounis syndrome) and hypersensitivity myocarditis following COVID-19 vaccination.

Rare acute hypersensitivity myocardial infarction (Kounis syndrome) and hypersensitivity myocarditis following COVID-19 vaccination.

Hymenoptera heartaches -cardiac manifestation with hymenoptera stings, a retrospective study from a tertiary care hospital in South India.

Hymenoptera stings usually have a multitude of presentations from very subtle to life-threatening conditions. Various cardiac manifestations including Kounis syndrome often get missed due to lack of suspicion. The aim of the study was to describe the clinical profile of the cardiac etiologies associated with hymenoptera stings and review literature with focus on diagnosis and treatment strategies. A retrospective chart analysis was performed including all adult patients who had a hymenoptera sting during a two-year window (October 2018 - October 2020). Of these, patients with cardiac features were enrolled. A structured case record form was used to capture information like basic demography, clinical profile, and outcomes. Thirteen cases presented with hymenoptera stings of which six cases had cardiac presentation and were considered. The most common presentations were breathlessness and generalised itching with only one patient complaining of chest pain. All patients(with available data) had ECG changes suggestive of ischemia and associated raised troponin levels with 2D echo changes. The diagnoses considered included Kounis syndrome, hypersensitivity myocarditis, and Takotsubo cardiomyopathy. Patients were managed conservatively with one patient undergoing a coronary angiography. All patients were stable at discharge. Cardiac manifestations with hymenoptera stings although rare may complicate diagnosis and treatment.It should be borne in mind during assessment and standardised guidelines should be developed for ED treatment such as the one recommended in this study.

Myocarditis Presenting as Sudden Death in Infants and Children: A Single Centre Analysis by ESGFOR Study Group.

Acute myocarditis is an inflammatory disease of the heart mostly diagnosed in young people, which can present as sudden death. The etiology includes infectious agents (mostly viruses), systemic diseases and toxins. We aim to characterize infants and children with myocarditis at post-mortem presenting as sudden deaths. Retrospective evaluation of 813 post-mortems in infants and children dying suddenly and unexpectedly between 2009-2019. Data retrieved included histological features, microbiology and clinical history. 23 of 813 post-mortems reviewed corresponded to acute myocarditis and 1 to dilated cardiomyopathy related to remote Parvovirus infection. PCR identified enterovirus (7), parvovirus (7 cases, 2 also with HHV6 and 1 case with EVB), Influenza A (1), Parainfluenza type 3 (1). Two cases corresponded to hypersensitivity myocarditis, 1 was Group A Streptococcus and 5 idiopathic myocarditis. Enterovirus was frequent in infants (7/10), and in newborns was associated with meningoencephalitis or congenital myocarditis. More than 50% were less than 2 years of age and all remained clinically unsuspected. Myocarditis represents almost 3% of all sudden pediatric deaths. Enterovirus and parvovirus were the most common viruses. This retrospective analysis showed that patients experienced viral symptoms but remained unsuspected, highlighting the need for more clinical awareness of myocarditis.

An urgent open surgical approach for left ventricle venting during peripheral veno-arterial extracorporeal membrane oxygenation for refractory cardiac arrest: case report

The objective of the study is to describe an emergency procedure for left ventricle venting during veno-arterial extracorporeal life support for refractory cardiac arrest. Veno-arterial extracorporeal membrane oxygenation is widely used in refractory cardiac arrest but is characterized by an increase in left ventricle afterload, which may impair cardiac contractility improvement. Different left ventricle venting techniques are available. We report the use of a surgical approach with sternotomy for left ventricle venting in a 21-year-old patient who was placed under veno-arterial extracorporeal membrane oxygenation for refractory cardiac arrest with severe pulmonary edema, respiratory failure, and left ventricle stasis. A 21-year-old woman was admitted for laparoscopic sleeve gastrectomy. In the recovery room, she developed a refractory circulatory shock. Transthoracic echocardiography revealed a dilated cardiomyopathy with severe left ventricle systolic dysfunction (left ventricle ejection fraction at 20%). Coronary angiogram was normal. On day 2, she underwent laparotomy for sepsis and she presented cardiac arrest secondary to ventricular tachycardia. We proceeded to peripheral veno-arterial extracorporeal membrane oxygenation as the cardiac arrest was refractory. A miniaturized veno-arterial extracorporeal membrane oxygenation system was implanted into the right femoral vessels onsite .The low flow duration was 40 minutes. Veno-arterial extracorporeal membrane oxygenation blood flow was set to 3 L min-1, resulting in a closed aortic valve and a massive pulmonary edema. Transesophageal echocardiography showed left ventricular ejection fraction at 5% without aortic valve opening. We first implanted an intra-aortic balloon pump without clinical improvement. Transesophageal echocardiography revealed massive thrombus formation into the aortic root. We decided to perform an open surgical approach for left ventricle unload using a transmitral cannula (22 Fr) via the right superior pulmonary vein connected to the inflow tube of the veno-arterial extracorporeal membrane oxygenation with Y connection. Transesophageal echocardiography showed a full opening of aortic valve and elimination of valve aortic thrombus. Chest radiography showed a significant decrease of pulmonary congestion. We were able to withdraw extracorporeal life support organization on day 10 and discharged on day 54. Clinical explorations reveal a fulminant rocuronium-related hypersensitivity myocarditis. This salvage surgical technique using a modified central veno-arterial extracorporeal membrane oxygenation cannulation technique has efficiently decreased blood stasis and permitted rapid recovery.

DRUG RASH WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS) SYNDROME HYPERSENSITIVITY MYOCARDITIS PRESENTING WITH CARDIOGENIC SHOCK

Introduction DRESS Syndrome can vary in presentation from mild to life threatening. We report a case of suspected DRESS myocarditis presenting with cardiogenic shock. Case Description A 38-year-old man presented to the ED with fever, dizziness, skin rash and facial swelling. Four weeks prior he was treated with amoxicillin/clavulanate for presumed sinusitis which was changed to sulfamethoxazole/trimethoprim and prednisone 30 mg daily 3 weeks later due to lack of improvement. Three days later he developed presenting symptoms. On ED admission, he was febrile (T =102.5F), tachycardic (HR 150 bpm) and hypotensive (BP 80/50 mmHg) with generalized erythematous macular skin rash and submandibular lymphadenopathy. Laboratory investigation revealed mildly elevated liver enzymes and creatinine, metabolic acidosis, hyponatremia and hypocalcemia, thrombocytopenia (125/nL) and absolute eosinophils of 0.30/nL. Chest x-ray was clear. He was hemodynamically stabilized with intramuscular followed by intravenous epinephrine and 6 liters intravenous fluids. Echocardiogram revealed severely reduced ejection fraction of 35% with diffuse hypokinesis. DRESS syndrome with hypersensitivity myocarditis was suspected. Treatment with prednisolone 80mg was initiated and laboratory abnormalities resolved within 5-10 days. A repeat echocardiogram 3 months later showed near normalization of EF (50-55%). Discussion Cardiac involvement in DRESS syndrome has been reported in 4 to 21 %. DRESS was suspected in this patient given regiSCAR and J-SCAR score of 5 in absence of peripheral eosinophilia (likely suppressed due to prior prednisone treatment). Clinicians should have a high suspicion for cardiac involvement in a patient presenting with suspected DRESS syndrome and hemodynamic compromise. Prompt diagnosis is crucial for successful treatment outcome.

Multi-modality Imaging in a Hypereosinophilic Syndrome with Cardiac Involvement

Introduction Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome, is a rare, multi-system auto-immune vasculitic disorder characterized by allergic rhinitis, asthma, and prominent peripheral blood eosinophilia. Cardiac involvement is the primary contributor to mortality. Case Report Mr. W is a 53-year-old man with a history of asthma and environmental allergies presented to the emergency department with sudden onset of blurred vision in his left eye and evidence of optic neuritis. He endorsed a 2-week history of night sweats, arthralgias, anorexia, transient ankle edema, and a recent rash. His exam was notable for purpuric lesions in extremities and left visual field deficits. Laboratory data showed a WBC's of 36,000 cells/mm3 with 69% eosinophils, CRP of 63 mg/dl, ESR of 122 mm/min, IgE of 1,741 IU/ml, and troponin of 11 ng/ml. An Electrocardiogram showed low voltage and q waves in anteroseptal leads. An infectious work-up was negative.A brain MRI revealed acute punctate infarcts. A transthoracic echocardiogram (TTE) revealed a severely dilated left ventricle with an ejection fraction of 25%. Cardiac catheterization showed normal coronary arteries, elevated filling pressures, and normal cardiac output. Cardiac Magnetic Resonance (CMR) showed moderate to severe biventricular dysfunction, a moderate pericardial effusion, and patchy bi-ventricular subendocardial enhancement ( Figure 1 A). So he underwent endomyocardial biopsy, which showed increased perivascular eosinophils/eosinophilic degranulation and fibrin ( Figure 1 B). The differential diagnosis was EGPA, hypersensitivity myocarditis or a myeloproliferative variant of hypereosinophilic syndrome. A bone marrow biopsy was performed which showed hypereosinophilia ( Figure 1 C), without evidence of malignancy, confirming EGPA. He was treated with high dose steroids with a prolonged taper and cyclophosphamide, which rapidly resolved his eosinophilia. A repeat TTE 7 weeks later showed near normalization of cardiac function and resolution of pericardial fluid. Conclusion Cardiac involvement in EGPA is up to 60% and early development of myocardial fibrosis. Prompt recognition via multi-modality imaging and endomyocardial biopsy and rapid treatment with high dose steroids or other immunotherapies, may prevent early progression to dilated or restrictive cardiomyopathy.

Myocarditis: A Rare Complication of 5-ASA Therapy

Introduction: Mesalamine is an unconjugated 5-aminosalicylate (5-ASA) approved for the treatment of inflammatory bowel disease (IBD). Developed as an alternative to sulfasalazine the 5-ASA agents are well tolerated with a favorable safety profile, but concerning side effects include paradoxical colitis, pancreatitis, pneumonitis, and nephrotoxicity. We present the case of hypersensitivity myocarditis, an exceedingly rare complication of mesalamine therapy. Case Report: A 27-year-old male with recently diagnosed Crohn's disease well controlled on oral mesalamine started three weeks prior presented with two days of sharp chest pain improved with sitting upright. He was tachycardic and hypotensive despite IV fluid resuscitation. Initial labs revealed normal lactate, but elevated inflammatory markers, troponin I (0.92ng/mL), and BNP (3753pg/mL). EKG was without ischemic changes and echocardiogram showed reduced systolic function, EF 25-30% with biventricular dilation. He was admitted to the ICU, started on IV steroids, and mesalamine discontinued. Cardiac MRI demonstrated late enhancement of the subepicardial lateral wall consistent with myocarditis. Extensive infectious and rheumatologic workup was unremarkable and the patient rapidly improved without further intervention. The heart failure service recommended right heart catheterization with endomyocardial biopsy, however, the patient declined. The etiology was determined a hypersensitivity myocarditis secondary to recent mesalamine use. He was discharged on prednisone and continued to improve at outpatient follow up. Discussion: Myocarditis is an incredibly rare complication of 5-ASA therapy with unknown prevalence. Two years of mesalamine safety data in France identified three possible cases of myocarditis of 130 adverse events, but is otherwise limited to case reports. Deemed a hypersensitivity reaction, patients respond rapidly to withdrawal of agent and have immediate recurrence when re-challenged. It is dose independent occurring days to months after exposure and may be delayed by steroid use. Misdiagnosis is common as it mimics serositis, a known reactive extraintestinal manifestation of IBD mirroring intestinal activity. There is no definitive diagnosis, however, correlation with recent 5-ASA initiation and myocardial biopsy showing eosinophilic infiltration are highly suggestive. Fatalities are documented but early identification is crucial as patients will do well with cessation of medication.

Clinical Vignettes/Case Reports - Inflammatory Bowel Disease.

Mesalamine (5-aminosalycilic acid) is a first line anti-inflammatory agent used for treatment of inflammatory bowel disease. Mesalamine is thought to reduce colonic inflammation by inhibiting the cyclooxygenase pathway and the γ-form of peroxisomal proliferator-activated receptors (PPAR-γ) signaling pathway. A 30-year-old male with a medical history significant for ulcerative colitis diagnosed 1 year prior, presented with chest pain, fever, chills, and generalized weakness. His symptoms began spontaneously six hours prior to coming to the Emergency room. The patient described a localized chest pain to his mid-sternum, that was sharp, non-radiating, and unalleviated by over-the-counter analgesics. He denied pleurisy, shortness of breath, diaphoresis, palpitations. His chest pain resolved after aspirin 325 mg and 0.5 inch topical nitroglycerin at the emergency department. The patient gave a history of starting budesonide 9 mg QD and an increase in his mesalamine dose from 800 mg to 1600 mg TID, 6 weeks prior. These medication regimen change occurred after an ulcerative colitis flair which developed after the patient had stopped taking his mesalamine for 2 weeks. His initial electrocardiogram showed normal variant study. Chest xray was negative. The case was discussed with his primary gastroenterologist and on-call cardiologist. Considering the strong association of the patients' recent symptoms with increase in his mesalamine dose, only budesonide was continued at admission. Subsequently, TEE showed grade II left ventricular dysfunction and left ventricular ejection fraction of 61 %. After thorough clinical evaluation, the patient was diagnosed with mesalamine-induced-myocarditis, and cardiac catherization was deferred, with recommendations for supportive care. Mesalamine induced-myocarditis is rare. The exact mechanism of which is unclear, but is thought to be secondary to a hypersensitivity reaction rather than direct myocardiotoxicity. This ideology of hypersensitivity myocarditis is supported by cases of acute recurrence of pleuropericarditis with re-exposure to mesalamine. Mesalamine-induced myocarditis has been associated with chronic use, often more than not with a recent increase in dosage in patients who are also concomitantly taking steroids as exemplified in our case. We hope that this report will further increase the awareness of prescribers to myocarditis caused by an increased dosage of mesalamine and with its chronic use.