Shin'ichiro Morimoto

Questionnaires were sent to 46 hospitals of all over Japan in order to obtain the clinical data on sarcoidosis patients who were treated with oral corticosteroids. The number of female patients was greater than that of male patients (1.5:1), and the average age was 44.9 +/- 16.5 with peaks at 20 and at 50 to 60. The markers of disease activity were high in serum or bronchoalveolar lavage fluids (BALF): specifically, the serum angiotensin-converting enzyme (sACE) was 27.9 +/- 31.9 IU/ml (n.v. < 21.4), and the CD4/CD8 lymphocyte ratio was 6.5 +/- 5.7. Eye involvement was the most common reason for systemic steroid therapy, followed in order by lung and heart involvement. The main reasons for steroid therapy were the exacerbation of ocular symptoms, visual disturbance, respiratory symptoms, such as cough or exertional dyspnea, progression of chest radiographic findings, heart failure and severe arrhythmia, such as AV block. The initial corticosteroid dose was usually 30 mg of predinisolone per day, but for some refractory cases, a 40-60 mg per day was used. Immunosuppressive drugs, such as methotrexate, were also used in the small number of patients who responded poorly to the steroid. Overall, a good clinical response to the drug was found in 70-80% of the steroid treated patients, but in those with cardiac disease, the response rate was only 48%.

In many cases, the diagnosis of eosinophilic myocarditis is suggested by an elevated peripheral blood eosinophil count. However, no detailed studies have been performed on the sequential changes in the initial peripheral blood eosinophil count over the course of the disease. We measured the peripheral blood eosinophil count at the time of presentation in eight patients with eosinophilic myocarditis proven by endomyocardial biopsy and intermittently thereafter. The eosinophil count at the time of onset was <500/mm(3) in four patients, >500/mm(3) but <1000/mm(3) in three patients, and greater than or equal to1000/mm(3) in one patient. In three of the four patients with an initial eosinophil count of <500/mm(3), an increase to greater than or equal to500/mm(3) occurred 7-12 days after the onset. The remaining patient did not develop peripheral eosinophilia. In conclusion, in the early stage of eosinophilic myocarditis, peripheral hypereosinophilia is not present initially in some patients, and may not develop during the course of the illness in a subset of these patients.

Background: The usefulness of corticosteroid therapy for cardiac sarcoidosis has not yet been fully clarified. Methods: Of 40 patients diagnosed with cardiac sarcoidosis, twenty patients complicated by atrioventricular block but normal cardiac function (left ventricular ejection fraction greater than or equal to50%) were divided retrospectively into one group (n = 7) receiving corticosteroids and another (n=13) not receiving these agents. Over a mean observation period of 79.4 +/- 39.9 months, long-term outcome and laboratory findings were compared between the two groups and side effects also were noted. Results: There were no deaths in the corticosteroid-treated group. In the untreated group, 2 patients died (15.4%). Atrioventricular block resolved in 4 of the 7 patients in the treated group (57.1%), but did not resolve or improve in any of the untreated patients (p < 0.05). Left ventricular ejection fraction did not differ significantly between the treated and untreated groups at the time of initial evaluation (66.7 +/- 6.5% vs. 60.5 +/- 6.4%). In the follow-up period, a marked decline in the ejection fraction had occurred in the untreated group (37.6 +/- 17.3%), but not in the treated group (62.1 +/- 4.4%; p < 0.005). Ventricular tachycardia was not present at the initial assessment in any patient in either group. In the follow-up period, ventricular tachycardia occurred in only 1 of 7 treated patients (14.3%), but was present in 8 of 13 untreated patients (61.5%; p<0.05). However, side effects of corticosteroid therapy were noted in 6 of the 7 treated patients (85.7%). Conclusion: Our findings suggest that corticosteroids are useful in the treatment of cardiac sarcoidosis complicated by atrioventricular block but with normal cardiac function. However, these agents must be used with caution, with the maintenance dose kept as low as possible.

Because of the marked side effects associated with conticosteroid use, a switch was made to methotrexate therapy in 4 patients with cardiac sarcoidosis and the utility of this agent was investigated. As side effects induced by methotrexate, anaplastic anemia developed in one case and liver dysfunction in two. In the former case, when this agent was discontinued and G-CSF (granulocyte-colony stimulating factor) filgrastim was administered, swift improvement was attained. In the two cases with liver dysfunction, dosage reduction was required. In the remaining case, despite the absence of obvious side effects, the switch to this agent was associated with a resurgence of sarcoidosis activity, necessitating a switch back to cordicosteroid administration. Accumulation of further experience with methotrexate therapy for cardiac sarcoidosis is awaited. Our present experience was not promising in that methotrexate therapy could not be considered effective in 3 of the 4 cases.