FINAL DIAGNOSIS: IDIOPATHIC GIANT CELL MYOCARDITIS.
Idiopathic giant cell myocarditis was first described in 1905 by Saltykow (1) and has in the past been synonymously referred to as Fiedler's myocarditis. It is a rare and often rapidly fatal form of myocarditis of unknown etiology. The majority of patients present with congestive cardiac failure or conduction disturbances. Post mortem examinations have shown the conduction disturbances to be due to bilateral bundle branch block secondary to involvement of the interventricular septum by the inflammatory process (2). Segmental wall motion disturbances have been demonstrated (2), suggesting that giant cell myocarditis (GCM) can be a focal as well as a diffuse process at specific stages of its evolution. Idiopathic giant cell myocarditis is, for the most part, a disease of young and previously healthy adults with reported mean ages of 37 years (five patients), 48 years (five patients) and 42.6 +/- 12.7 years (sixty three patients), in three different series (2-4). The youngest patient reported was six weeks old (5) and the oldest 88 years old (6). The relative infrequency of reported cases in the elderly may be partially attributable to a more or less fulminant course of disease in this population, as well as to a decreased level of suspicion in these patients who often have other cardiovascular problems, as in this patient.
Many autoimmune disorders have been cited to be associated with GCM, including Hashimoto's thyroiditis, myasthenia gravis, ulcerative colitis, rheumatoid arthritis, pernicious anemia, Takayasu's arteritis and orbital myositis (2,7,8). One recent series reported 19% of sixty three patients to have an associated autoimmune disorder (4). These associations, and the reproducibility of experimental GCM in Lewis rats by autoimmunization with myosin (9), suggest that it is an autoimmune disorder dependent on CD-4 positive T lymphocytes. Further support for an autoimmune etiology is the reported response to immunosuppressive therapy. Although this patient had a history of hypothyroidism, there was no previous diagnosis of Hashimoto's thyroiditis, nor was there available laboratory data to substantiate this. Forthermore, the restrictions imposed on the autopsy prevented post mortem examination of the thyroid gland.
The gross and microscopic features described in this case are quite characteristic of this entity, the only exception being biventricular hypertrophy. Most patients described have cardiomegaly with biventricular dilatation, but in this elderly patient with severe coronary artery disease, there was an element of superimposed hypertrophy.
Several controversial issues have surround this uncommon and poorly understood entity. One such debate is the origin of the giant cells. Earlier authors have suggested a myogenic origin, since the giant cells are often located adjacent to necrotic myocytes and ultrastructural observations have shown them to contain cytoplasmic fibrils interpreted as myofilaments (6,10). However, with the advent of immunohistochemical stains, a monocyte / macrophage lineage of the giant cells, showing positive immunoreactivity with KP-1 (CD68) and an absence of staining with the muscle markers, actin and desmin, has been confirmed (2,7,11). In addition, there is ultrastructural evidence of a histiocytic origin, with abundant sarcoplasmic reticulum and cytoplasmic lysosomal vacuoles in these cells (2). A plausible explanation for the cytoplasmic myofilaments previously described is phagocytic engulfment of damaged myofilaments.
The possible relationship to differentiation of GCM and cardiac sarcoidosis has been yet another point of contention. Some authors do not distinguish between GCM and cardiac sarcoidosis (12,13), buts most recent studies suggest that the former is a distinct and well-defined entity (6,14,15). Suggested histopathological differences between the two include:
Clinical trials have suggested immunosuppressive therapy with regimens which include cyclosporine, azathioprine or both, may prolong life. Corticosteroids alone have not been therapeutically successful (2,4). The ultimate possibility for long term survival is cardiac transplantation. Noteworthy, however, are thirteen reported cases of recurrent idiopathic giant cell myocarditis in the transplanted heart, some of which were fatal (4).
Contributed by Shashi Ariyanayagam-Baksh, MBBS