ROLE OF METHYLPREDNISOLONE IN EARLY PREDICTED DIPHTHERIC CARDIOMYOPATHY IN CHILDREN: IS THIS A SOLUTION?
Keywords:Diphtheria, cardiomyopathy, Children, Methylprednisolone, Steroids
AbstractBackground: Diphtheria remains an important cause of paediatric mortality in developing countries. The mortality rate is still ∼10% and has changed little over the past 20 years with particular reference to developed world. The objective of this study is to examine clinical spectrum of diphtheric cardiomyopathy and by using tools (serum markers, ECG, Echocardiography) to predict the cardiomyopathy and role of steroids in these predicted patients. Methods: For this cohort study, 67 patients having diphtheria presenting for the first time in a 3-year period were enrolled after obtaining informed verbal consent from the guardian of each child. Demographical profile, vaccination status, clinical spectrum, ECG interpretation and echocardiographic findings were recorded that predicted the occurrence of diphtheric cardiomyopathy and used intravenous methylprednisolone pulses in these predicted patients to look for their outcome regarding change in severity or the fate in the form of mortality. Results: Among the 67 enrolled children (M: F 2.3:1) with age ranging from 24 to 172 months (median 106 months), 56.7% subjects presented with diphtheria were non-vaccinated. 37.3% had a cardiac involvement in the form of diphtheria cardiomyopathy or arrhythmia.7.5% patient expired on follow up. Presence of septal paradoxes on echo had association with the cardiac involvement (OR 10.1: 95% CI 1.2-84.6; p=0.0005). IV methyl prednisolone was given in all 37.3% (n=25) patients predicted as diphtheric cardiomyopathy (Asymptomatic) and 88 %(n=22) had a favourable outcome with no morbidity and mortality. 12% (n=3) were expired and they presented with shock and VT as their first presentation (symptomatic). Conclusion: Early prediction by alone or in combination of ECG and echocardiographic markers and early use of IV methyl prednisolone in these predicted patients before symptoms, can reduce the mortality related to diphtheric cardiomyopathy and can decrease the burden of the disease in the community. Further randomized controlled trials with a larger sample size are required to unambiguously delineate the prognostic value of steroids in early predicted diphtheric cardiomyopathy.
White NJ, Hien TT. Diphtheria. In: Cook GC, editor. Manson’s tropical diseases. 20th ed. London: Saunders, 1996; p.931–5.
Rakhmanova AG, Lumio J, Groundstroem K, Valova E, Nosikova E, Tanasijchuk T, et al. Diphtheria outbreak in St. Petersburg: clinical characteristics of 1860 adult patients. Scand J Infect Dis 1996;28(1):37–40.
Wesley AG, Pather M, Chrystal V. The haemorrhagic diathesis in diphtheria with special reference to disseminated intravascular coagulation. Ann Trop Paediatr 1981;1(1):51–6.
Sharma NC, Efstratiou A, Mokrousov I, Mutreja A, Das B, Ramamurthy T. Diphtheria. Nat Rev Dis Primers 2019;5(1):81.
Jayashree M, Shruthi N, Singhi S. Predictors of outcome in patients with diphtheria receiving intensive care. Indian Pediatr 2006;43(2):155–60.
Bethell DB, Nguyen Minh Dung, Ha Thi Loan, Le Thi Nguyet Minh, Nguyen Quoc Dung, Day NP, et al. Prognostic value of electrocardiographic monitoring in severe diphtheria. Clin Infect Dis 1995;20(5):1259–65.
Stockins BA, Lanas FT, Saavedra JG, Opazo JA. Prognosis in patients with diphtheric myocarditis and bradyarrhythmias: assessment of results of ventricular pacing. Br Heart J 1994;72(2):190–1.
Havaldar PV, Sankpal MN, Doddannavar RP. Diphtheritic myocarditis: Clinical and laboratory parameters of prognosis and fatal outcome. Ann Trop Paediatr 2000;20(3):209–15.
Varghese MJ, Ramakrishnan S, Kothari SS, Parashar A, Juneja R, Saxena A. Complete heart block due to diphtheritic myocarditis in the present era. Ann Pediatr Cardiol 2013;6(1):34–8.
Thisyakorn U, Wongvanich J, Kumpeng V. Failure of corticosteroid therapy to prevent diphtheritic myocarditis or neuritis. Pediatr Infect Dis 1984;3(2):126–8.
Matsumura T, Tajima S. Favorable effects of corticosteroids in the treatment of diphtheria. J Asthma Res 1973;11(2):63–75.
Kneen R, Nguyen MD, Solomon T, Pham NG, Parry CM, Nguyen TT, et al. Clinical Features and Predictors of Diphtheritic Cardiomyopathy in Vietnamese Children. Diphtheritic Cardiomyopathy in Children. Clin Infect Dis 2004;39(11):1591–8.
Kole AK, Roy R, Kar SS. Cardiac involvement in diphtheria: Study from a tertiary referral infectious disease hospital. Ann Trop Med Public Health 2012;4:302–6.
WHO. Country Cooperation Strategy for WHO and Pakistan 2011–2017. [Internet]. [cited 2021 May]. Available from: http://www.who.int/countryfocus/cooperation_strategy/ccs_pak_en.pdf
Pakistan Bureau of Statistics. Population size and growth of major cities. 1998.
Burkhardt E, Eggleston C, Smith L. Electrocardiographic changes and peripheral nerve palsies in toxic diphtheria. Am J Med Sci 1938;195:301–38.
Zakilkhany K, Efstratiou A. Diptheria in Europ: Current problems and new challenged. Future Microbial 2012;7(5):595–607.
Khan MH, Aurakzai AA, Irshad M, Ullah H. Complications and outcome of Diphtheria in admitted pediatric patients at a tertiary care setting in Peshawar. J Postgrad Med Inst 2018;32(3):242–5.
Sharland M, Butler K, Cant A, Dagan R, Davies G, de Groot R, et al, editors. Manual of childhood infections: 4th ed. the blue book. Oxford University Press, 2016; p.520–3.
Lumio JT, Groundstroem KW, Melnick OB, Huhtala H, Rakhmanova AG. Electrocardiographic abnormalities in patients with diphtheria: A prospective study. Am J Med 2004;116(2):78–83.
Harwalkar KK, Kadegaon B. Clinical profile of children with diphtheria admitted to tertiary care center. Indian J Child Health 2019;6(10):563–5.
Mason JW, O’Connell JB, Herskowitz A, Rose NR, McManus BM, Billingham ME, et al. A clinical trial of immunosuppressive therapy for myocarditis. The myocarditis treatment trial investigators. N Engl J Med 1995;3(333):269–75.
Pleasure D, Messing A. Chapter 95 – diphtheritic Polyneuropathy. In: Dyck PJ, Thomas PK, editors. Peripheral neuropathy. 4th ed. Philadelphia: Saunders, 2005; p.2147–51.
Magill AJ, editor. Hunter’s tropical medicine and emerging infectious diseases. Ninth edition. London: Saunders/Elsevier, 2013; p.402–6.
Yu H, Wu M, Lu G, Cao T, Chen N, Zhang Y, et al. Prednisone alleviates demyelination through regulation of the NLRP3 inflammasome in a C57BL/6 mouse model of cuprizone-induced demyelination. Brain Res 2018;1678:75–84.