Hypersensitivity, Eosinophilic, and Toxic Myocarditis



Hypersensitivity, Eosinophilic, and Toxic Myocarditis


Allen P. Burke, M.D.





Hypersensitivity and Eosinophilic Myocarditis


Incidence

Symptomatic hypersensitivity myocarditis, especially when documented histologically, is rare and generally the subject of case reports. The incidence of incidental hypersensitivity myocarditis diagnosed initially at autopsy is high, about 2% to 5%, depending on the population and history of medication use. In patients awaiting transplant, who are often on multiple medications, the incidence is 2% to 7%, as diagnosed histologically in the explanted heart or left ventricular apex removed at time of assist device insertion.1,2


Pathogenesis

Hypersensitivity is due to a delayed hypersensitivity reaction, and not a toxic effect of the offending drug. It has been postulated that modified collagen may be a trigger for eosinophilic reaction and degranulation.3

Many drugs have been histologically associated with hypersensitivity myocarditis.4 A smaller number have been implicated in symptomatic hypersensitivity myocarditis diagnosed histologically (generally by endomyocardial biopsy) (Table 164.1).

In incidentally found hypersensitivity myocarditis at autopsy and explants, a specific drug is rarely identified, because of multiple medication history.

Eosinophilic myocarditis may also be the result of mechanisms other than hypersensitivity. Churg-Strauss syndrome, parasitic infection, and chronic eosinophilic leukemia can result in eosinophilic infiltrates in the myocardium, often with myocyte necrosis. In some patients, an underlying cause or offending agent is never found.26


Clinical Findings

Clinical manifestations of hypersensitivity myocarditis fall into two groups of patients: those diagnosed during life, who have severe, often life-threatening symptoms (more often termed “eosinophilic myocarditis),” and those diagnosed at explant or autopsy, who often have no symptoms. The term “acute necrotizing eosinophilic myocarditis” has been used for the most severe form of hypersensitivity myocarditis that causes rapidly progressive congestive heart failure.27,28









TABLE 164.1 Drugs Associated with Hypersensitivity Myocarditis Diagnosed Pathologically









































































Medication


Symptom


Reference


Amoxicillin


Heart failure, chest pain, acute coronary syndrome


Sudden death


5


6 (Giant cells)


7 (No giant cells)


Ciprofloxacin


Cardiogenic shock


8


Cephalosporin (cefaclor)


Heart failure


9


Cephalosporins (2)


Heart failure and death


10


Dobutamine


Heart failure


11


12


Clozapine


Sudden deatha


Heart failure, fever


13


14


Metoprolol


Heart failure


15


Azithromycin


Fever, rash, heart failure, DRESS syndrome


16


Mesalamine


Chest pain, heart failure


17


Ephedra


Heart failure


18


Sulfasalazine


Cardiogenic shock (Fatal)


19 (Had giant cells on biopsy)


20 (No giant cells)


Isoniazid


Rash, myocarditis


21


Antituberculous drugs (multiple)


Myocarditis, heart failure


22


Herbal supplements


Heart failure, ventricular arrhythmias


23


Adalimumab


Fatal cardiogenic shock


24


No agent identified


Heart failure


25


a Diagnosed made at autopsy. Others in table were diagnosed by biopsy.


Patients with symptomatic hypersensitivity myocarditis often present with signs and symptoms of myocarditis, often with heart failure. The symptoms generally occur within weeks after exposure to agent and generally resolve after withdrawal of the drug. The cardiac symptoms may be accompanied by a skin rash. Other manifestations of systemic hypersensitivity, including peripheral eosinophilia, may accompany hypersensitivity myocarditis (drug-induced rash with eosinophilia and systemic symptoms).5,21,29,30 Hypersensitivity myocarditis causing severe heart failure has been reported complicating Stevens-Johnson syndrome.19






FIGURE 164.2 ▲ Hypersensitivity myocarditis. In this explanted heart in a transplant recipient, there are scattered interstitial infiltrates, without myocyte damage. A. There is interstitial inflammation with eosinophils and mononuclear cells. B. A higher magnification shows marked interstitial inflammation with prominent eosinophils.






FIGURE 164.1 ▲ Hypersensitivity myocarditis. There is a sparse interstitial infiltrate, without any myocyte damage. Focal interstitial infiltrates are a common finding at autopsy, especially in patients on multiple medications.

Most patients respond to steroids and drug cessation.22,23,25,31,32 Irreversible heart failure may lead to cardiogenic shock and death, or heart transplantation.7,19,20

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Aug 19, 2016 | Posted by in CARDIOLOGY | Comments Off on Hypersensitivity, Eosinophilic, and Toxic Myocarditis

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