Mechanical respiratory obstruction and myocarditis account for most diphtheria-related deaths.[27]Acosta AM, Pedro LM, Hariri S et al. Diphtheria. In: Hall E, Wodi AP, Hamborsky J, et al. Centers for Disease Control and Prevention. Epidemiology and vaccine-preventable diseases. 14th ed. Washington, DC. Public Health Foundation, 2021.
https://www.cdc.gov/pinkbook/hcp/table-of-contents/chapter-7-diphtheria.html
The overall case fatality rate for diphtheria was 2.4% in the 1940s and remained at 2% to 3% in the Russian outbreak of the 1990s. If diphtheric polyneuropathy develops, mortality of 16% has been reported.[59]Logina I, Donaghy M. Diphtheritic polyneuropathy: a clinical study and comparison with Guillain-Barre syndrome. J Neurol Neurosurg Psychiatry. 1999 Oct;67(4):433-8.
http://www.ncbi.nlm.nih.gov/pubmed/10486387?tool=bestpractice.com
Before the era of effective treatment, the case-fatality rate was approximately 50%; with treatment and vaccination more widely available, the case-fatality rate has remained at approximately 10%.[1]Centers for Disease Control and Prevention. Manual for the surveillance of vaccine-preventable diseases. Chapter 1: diphtheria. Dec 2022 [internet publication].
https://www.cdc.gov/vaccines/pubs/surv-manual/chpt01-dip.html
In 2017-2019, the largest diphtheria outbreak of the current century, among Rohingya refugees in Bangladesh, was associated with a much lower mortality rate of 0.5%.[22]Truelove SA, Keegan LT, Moss WJ, et al. Clinical and epidemiological aspects of diphtheria: a systematic review and pooled analysis. Clin Infect Dis. 2020 Jun 24;71(1):89-97.
https://www.doi.org/10.1093/cid/ciz808
http://www.ncbi.nlm.nih.gov/pubmed/31425581?tool=bestpractice.com
[23]Polonsky JA, Ivey M, Mazhar MKA, et al. Epidemiological, clinical, and public health response characteristics of a large outbreak of diphtheria among the Rohingya population in Cox's Bazar, Bangladesh, 2017 to 2019: A retrospective study. PLoS Med. 2021 Apr;18(4):e1003587.
https://www.doi.org/10.1371/journal.pmed.1003587
http://www.ncbi.nlm.nih.gov/pubmed/33793554?tool=bestpractice.com
Recovery of cardiac function is usually complete following myocarditis. However, patients who experience severe arrhythmias may sustain permanent damage to the cardiac conduction system.[4]Padhye A, Fritz SA. Diphtheria. In: Kliegman R, St Geme JW, Blum NJ, et al., eds. Nelson textbook of pediatrics. 21st ed. Philadelphia, PA: Elsevier; 2020.
Usually there is complete resolution of neurological deficits. Rarely, dysfunction of the vasomotor centres can lead to hypotension and heart failure.[4]Padhye A, Fritz SA. Diphtheria. In: Kliegman R, St Geme JW, Blum NJ, et al., eds. Nelson textbook of pediatrics. 21st ed. Philadelphia, PA: Elsevier; 2020.
Patient age and immunisation status are important prognostic factors: very old and very young people generally have a poorer prognosis, while previous immunisation is associated with a better prognosis.
The timing of diphtheria antitoxin therapy is crucial to outcome; early administration can prevent many of the toxic sequelae of the disease.[4]Padhye A, Fritz SA. Diphtheria. In: Kliegman R, St Geme JW, Blum NJ, et al., eds. Nelson textbook of pediatrics. 21st ed. Philadelphia, PA: Elsevier; 2020. Skin infections rarely cause systemic symptoms.[2]Centers for Disease Control and Prevention. Diphtheria: clinical features of diphtheria. Feb 2024 [internet publication].
https://www.cdc.gov/diphtheria/hcp/clinical-signs
[3]Moore LSP, Leslie A, Meltzer M, et al. Corynebacterium ulcerans cutaneous diphtheria. Lancet Infect Dis. 2015 Sep;15(9):1100-07.
http://www.ncbi.nlm.nih.gov/pubmed/26189434?tool=bestpractice.com