Outcomes of Purpura FULminans in Adults - The hOPeFUL Study

Purpura fulminans (PF) is a rare life-threatening infectious disease characterized by the association of a sudden and extensive purpura together with acute circulatory failure. Neisseria meningitidis and Streptococcus pneumoniae are the most frequently involved microorganisms but other species (e.g., Staphylococcus aureus, Streptococcus pyogenes, Haemophilus influenzae…) have also been reported. Despite prompt antibiotics administration and intensive care management, the mortality of PF has been reported to be as high as 50% in previous adult series. Additionally, patients surviving to the early phase of PF are exposed to a high risk of serious sequelae related to extensive skin necrosis and acral symmetrical gangrene, which typically requires limb amputations, a potential source of severe handicap in these previously young and healthy patients. Although the clinical features and outcomes of PF have been well studied in the pediatric setting, the amount of available data for adult PF are scarce, often outdated and mainly limited to patients with meningococcal infections. The current study aims at assessing the short and long-term outcomes of adult patients admitted in the intensive care unit for a purpura fulminans. A large multicenter retrospective cohort will be built in order to assess hospital outcomes (i.e., mortality and amputations). Long-term outcomes, including health-related quality variables, will be prospectively assessed among survivors and compared to septic controls (i.e., patients having septic shock non-related to purpura fulminans).

• Phone interview measuring health-related quality of life variables (Other): A phone interview will be conducted by a dedicated nurse who will be blinded to the exposed/non-exposed status of the patient.

Primary outcomes

• Hospital mortality [day 60]: factors associated with hospital mortality (and rate of amputation in the hospital) will be identified using a polytomous logistic regression model
• Rate of amputation in the hospital; [day 60]: factors associated with rate of amputation in the hospital (and hospital mortality) will be identified using a polytomous logistic regression model
• Long-term outcome measure: Physical dimension scale of the SF-36 questionnaire [Within 6 years of hospital discharge]: This variable will be compared between patients with purpura fulminans and patients with septic shock non-related to purpura fulminans

Secondary outcomes

• Mental component score of the SF-36 score [Within 6 years of hospital discharge]: This variable will be compared between patients with purpura fulminans and patients with septic shock non-related to purpura fulminans
• Activity of daily living (ADL score) [Within 6 years of hospital discharge]: This variable will be compared between patients with purpura fulminans and patients with septic shock non-related to purpura fulminans
• Hospital anxiety and depression scale [Within 6 years of hospital discharge]: This variable will be compared between patients with purpura fulminans and patients with septic shock non-related to purpura fulminans
• Impact of Event Scale [Within 6 years of hospital discharge]: This variable will be compared between patients with purpura fulminans and patients with septic shock non-related to purpura fulminans
• Physical dimension scale of the SF-36 questionnaire [Within 6 years of hospital discharge]: This variable will be compared between patients with purpura fulminans who were and those who were not amputated
• Mental component score of the SF-36 score [Within 6 years of hospital discharge]: This variable will be compared between patients with purpura fulminans who were and those who were not amputated

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Patients admitted in the intensive care unit between 2010 and 2016 for an infectious purpura fulminans and discharged alive

Exclusion Criteria:

* Age < 18 years
* Non infectious purpura
* Infective endocarditis

• Results publication: Giraud T, Dhainaut JF, Schremmer B, Regnier B, Desjars P, Loirat P, Journois D, Lanore JJ. Adult overwhelming meningococcal purpura. A study of 35 cases, 1977-1989. Arch Intern Med. 1991 Feb;151(2):310-6. PMID 1992958
• Results publication: Lerolle N, Carlotti A, Melican K, Aubey F, Pierrot M, Diehl JL, Caille V, Hekimian G, Gandrille S, Mandet C, Bruneval P, Dumenil G, Borgel D. Assessment of the interplay between blood and skin vascular abnormalities in adult purpura fulminans. Am J Respir Crit Care Med. 2013 Sep 15;188(6):684-92. doi: 10.1164/rccm.201302-0228OC. PMID 23924269
• Results publication: Contou D, Canoui-Poitrine F, Coudroy R, Preau S, Cour M, Barbier F, Terzi N, Schnell G, Galbois A, Zafrani L, Zuber B, Ehrmann S, Gelisse E, Colling D, Schmidt M, Jaber S, Conia A, Sonneville R, Colin G, Guerin L, Roux D, Jochmans S, Kentish-Barnes N, Audureau E, Layese R, Alves A, Ouedraogo R, Brun-Buisson C, Mekontso Dessap A, de Prost N; Hopeful Study Group. Long-term Quality of Life in Adult Patients Surviving Purpura Fulminans: An Exposed-Unexposed Multicenter Cohort Study. Clin Infect Dis. 2019 Jul 2;69(2):332-340. doi: 10.1093/cid/ciy901. PMID 30335142
• Results publication: Contou D, Sonneville R, Canoui-Poitrine F, Colin G, Coudroy R, Pene F, Tadie JM, Cour M, Beduneau G, Marchalot A, Guerin L, Jochmans S, Ehrmann S, Terzi N, Preau S, Barbier F, Schnell G, Roux D, Leroy O, Pichereau C, Gelisse E, Zafrani L, Layese R, Brun-Buisson C, Mekontso Dessap A, de Prost N; Hopeful Study Group. Clinical spectrum and short-term outcome of adult patients with purpura fulminans: a French multicenter retrospective cohort study. Intensive Care Med. 2018 Sep;44(9):1502-1511. doi: 10.1007/s00134-018-5341-3. Epub 2018 Aug 20. PMID 30128591

• Nicolas de Prost, MD, PhD, Principal investigator, Henri Mondor University Hospital