Cyclophosphamide in pulmonary alveolar hemorrhage due to leptospirosis

Abstract

Background and Aims:Severe pulmonary involvement in leptospirosis carries high mortality rates. It is the most common cause of death due to leptospirosis in many parts of India and the world. Exacerbated immune response of the host plays an important role in its pathogenesis. Hence, immunosuppressive drugs could be useful in its treatment. Glucocorticosteroids have been found to be useful in several studies. Cyclophosphamide, an immunosuppressive agent, has been found to be useful in a majority of pulmonary alveolar hemorrhages due to non leptospiral causes. This study was carried out to study the effects of cyclophosphamide in patients with leptospiral pulmonary alveolar hemorrhage.Method:A total of 65 patients with confirmed leptospirosis with severe pulmonary involvement admitted to a tertiary care center in south Gujarat were included in the study. All of the patients were treated with injection crystalline penicillin, methyl prednisolone pulse therapy, and non invasive mechanical ventilation. A total of 33 patients were given parenteral cyclophosphamide 60 mg/kg body weight stat on diagnosis. Their outcomes were compared with the remaining 32 patients who had not been given this drug. Survival was considered the main outcome indicator.Results:Out of the 33 patients treated with cyclophosphamide, 22 (66.7%) survived, while in the control group out of 32 patients, three (9.4%) survived. On statistical analysis, the odds ratio was 19.33 (4.22–102.13) and the P-value was <0.001. Leucopenia (78.78%) and alopecia (18.75%) were the main side effects noted. No mortality was noted due to these side effects.Conclusion:Cyclophosphamide improves survival in cases of severe pulmonary alveolar hemorrhage due to leptospirosis. Statistically, the improvement is highly significant.

Effect of Methylprednisolone and Cyclophosphamide on the Survival of Patients with Leptospirosis, Renal Failure and Pulmonary Hemorrhage

“…This is consistent with previous studies showing a poor prognosis for patients with pulmonary hemorrhage [6]. Gancheva in their study on the hemorrhagic syndrome of leptospirosis showed that hemorrhages were found in 75% of death and were risk factors for death [9].…”

“…Sharma in their study in 2009 concluded that thrombocytopenia was an important contributory factor in the pathogenesis of hemorrhage in leptospirosis [12]. Trevendi Parameters HC N (percent) N=48 in 2010 also noted that there is an increase in the megakaryocytes in the bone marrow of patients with thrombocytopenia, suggesting peripheral destruction of platelets, which is most likely immune-mediated brought about by vasculitis [13]. Furthermore, the study by Gancheva et al [9] demonstrated the presence of anti-thrombocyte antibodies causing platelet destruction in severe leptospirosis [9].…”

“…A study by Trivedi et al [6] showed that among 33 patients treated with cyclophosphamide, 22 (66.7%) survived, while in 32 patients given standard therapy plus methylprednisolone alone, only three (9.4%) survived. Trivedi et al concluded that cyclophosphamide improved survival in cases of severe alveolar hemorrhage due to leptospirosis [6].…”

“…A study by Trivedi et al [6] showed that among 33 patients treated with cyclophosphamide, 22 (66.7%) survived, while in 32 patients given standard therapy plus methylprednisolone alone, only three (9.4%) survived. Trivedi et al concluded that cyclophosphamide improved survival in cases of severe alveolar hemorrhage due to leptospirosis [6]. The improvement in survival of patients using an immunosuppressive regimen, as shown in our study, further strengthens the possibility that an immune mechanism plays a key role in the pathogenesis of the disease.…”

“…Despite standard and supportive treatment, mortality still ranges from 5-20% [6,7]. Because of the more aggressive manifestations of the disease, trends in management are currently focusing on its immune aspect as a target for therapy.…”