Aetiology of myocarditis is highly varied (Tab. 1) and includes both infectious and non-infectious agents. The introduction of PCR and electron microscopy for the analysis of bioptically taken samples of the myocardium of patients with myocarditis had a big importance for the discovery of infectious agents causing the disease.
The most frequent cause of myocarditis and ICMP are considered infectious agents, whereas groups of viruses which are predominant in the aetiology of myocarditis and ICMP are changing depending of time and geographical location. For a long period of time, dominant agents of these conditions in Europe and North America were considered enteroviruses and adenoviruses. In present, they have been replaced by herpes viruses and parvovirus B19 (PVB19) [170]. The most frequent viral agents of myocarditis and ICMP generally are considered PVB19, human herpes virus 6, cytomegalovirus and Epstein-Barr virus [170]. However, results of the studies differ in the question of the extent of the representation of these viruses in aetiology of myocarditis and ICMP. In study published in 2012, including 203 with myocarditis who underwent EMB, genome of PVB19 was detected in 55,7 % of individuals, HHV-6 in 24,1 % and dual infection of PVB19 and HHV-6 in 17,2 % [27].
In a Czech study including 50 patients with DCMP who underwent EMB, viral genome was detected in 29 individuals, and 27 of these individuals (93 %) constituted PVB19 [28].
However, the importance of PVB19 in aetiology of myocarditis was repeatedly called into question because the genome of PVB19 was detected even in patients without no signs of myocarditis and ICMP [35].
Nevertheless, enteroviruses (primarily Coxsackie), adenoviruses, hepatitis C virus and influenza virus still remain relatively important viral agents of myocarditis and ICMP. In Japan, even cases of H1N1 virus myocarditis were described [20].
Bacteria are also no less important agents of myocarditis and ICMP. In the Czech Republic, myocarditis caused by Borellia burgdorferi has relatively often incidence [29]. In the developing countries, the disease may be caused even by meningococcus and diphteriae [22]. Primarily in the area of the Central and South America, infection of Trypanosoma cruzi dominates developing often in so called Chagas disease [26].
Nonnegligible parts of aetiology of myocarditis are also different cardiotoxic drugs, ethanol and addictive drugs (chemotherapeutics, cocaine), hypersensitive allergic reactions (e.g. by ATB or antidepressants) and systematic inflammatory disorders (primarily connective tissue diseases). As for the hypersensitive reactions caused by antidepressant, myocarditis was described as a complication for example in the therapy with clozapine. In Australian study from 1993 to 2003 including 116 patients treating with clozapine, its incidence varied between 0,7 to 1,2 %, including 10,3 % fatal cases of myocarditis [31].
Myocarditis remains a frequent complication in patients with HIV infection, especially in patients with AIDS when myocarditis is confirmed post-mortem in up to 52 % of individuals [32]. In up to 25 % of patients, HIV infection is connected with DCMP [34]. Pathogenesis of myocarditis in HIV positive patients remains still unclear. It may include a direct effect of the HIV virus on the myocardium or the development of myocarditis in these patients may be connected with the weakened immune system and myocarditis could be thus caused by a different agent, for example toxoplasmosis [33].
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| Viruses | Enteroviruses (Coxsackie, echoviruses), adenoviruses, influenza viruses, herpetic viruses (cytomegalovirus, HHV-6, Epstein Baar virus, varicella zoster virus), PVB19, hepatitis C virus, HIV, rubella, yellow fever, Dengue fever |
| Bacteria | Borellia burgdorferi, streptococcus, stafylococcus, mycobacterium, Chlamydiae, mycoplasma, legionella, corynobacterium diphteriae, treponema pallidum, neisseria, rickettsia, salmonella, Leptospira, brucella, bartonella, yersenia, Coxiella burnetti (Q fever), shigella, campylobacter jejuni, vibrio cholera, hemophilus influenzae, Francisella tularensis |
| Protozoans and parasites | Toxoplasma gondii, Trypanosoma cruzi, Plasmodium falciparum, Trichinella spiralis, schistosomiasis, toxocara canis, echinococcus, ascarida, entamoeba, leishmania, Taenia solium, Larva migrans |
| Fungi | Candida, cryptococcus, histoplasma, aspergillus, actinomyces, blastomyces, coccidioides, mucormycoces, nocardia, sporothrix |
| Toxic damage | Ethanol, anthracyclines, cocaine, anabolic steroids, heavy metals (cobalt, lead, iron, copper), substances of arsenic and phosphorus, corban oxide, catecholamines, snake, scorpion, spider, wasp and bee poison, lithium, amphetamines, cyclophosphamide, 5-phluorouracile, chloramphenicol, aminophylline, zidovudin, trastuzumab, methylsergid, mesylate, tetanus toxoid, colchicine |
| Hypersensitive (allergic) reactions | Antibiotics (penicillin, sulphonamides, tetracyclines, streptomycine, cefalosporines, azitromycin, chloramphenicol), antidepressants, anti-tuberculosis drugs (isoniasid, para-aminobutyric acid), anticonvulsants (fenindion, fenytoin, karbamazepin), diuretics (acetazolamid, chlorthalidon, spironolakton, hydrochlorothiazid), non-steroidal anti-inflammatory drugs (indometacin, oxyfenbutazon, fenylbutazon, ibuprofen), small-pox vaccine, mesalazin, dobutamin, methyldopa, sulfonylurea, digoxin, enalapril, captopril, lidocaine |
| Disease (primarily autoimmune) | Rheumatic fever, SLE, diabetes mellitus, ulcerative colitis, rheumatic arthritis, sarcoidosis, polymyositis, thyrotoxicosis, Wegener´s granulomatosis, Kawasaki disease, coeliac disease, Sjögren´s syndrome, Churg-Strauss syndrome, Hypereosinophilic syndrome, dermatomyositis, scleroderma, Crohn´s disease, myasthenia gravis |
| Others | Radiation, electric shock, gravidity, heart transplant rejection, hypothermia |
Table 1: Aetiology of myocarditis (based on references – 4, 8–18), bold the most common agents of myocarditis based on references 4, 8-18
Author of the opening picture: Thomas Splettstoesser
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References:
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