Purpura Fulminans in a 20-Year-Old Female

A previously healthy 20-year-old female presented with extensive retiform purpura located at the face, upper and lower limbs, one week after an episode of acute tonsillitis. Despite the exuberance of the cutaneous findings and progression to skin necrosis she had no accompanying symptoms. Laboratory investigation revealed a heterozygous protein C mutation (exon 9, c.1332G> C, p.Trp444Cys), accounting for a partial deficiency of this anticoagulant protein. The patient was started on broad spectrum antibiotics, anticoagulation and systemic corticosteroids, with no lesional progression and complete resolution of cutaneous ulceration within 6 months. This is a singular case of purpura fulminans, since two different causative factors precipitated the events. The previous tonsillitis reported by the patient is significant, because the serum concentration of protein S may also decrease after an infectious event - post-infectious purpura fulminans. This case illustrates that purpura fulminans due to autoantibodies against protein S, although rare, should be considered, especially in the absence of a severe acute infection. It also illustrates how in a given patient different independent factors can act simultaneously, triggering potentially devastating clinical scenarios.

Idiopathic purpura fulminans with anti-PS antibodies in children: a multicenter case series and systematic review

Idiopathic purpura fulminans (IPF) is a rare but severe pro-thrombotic coagulation disorder that can occur after chickenpox or HHV6 infection. IPF leads to an autoantibody-mediated decrease in the protein S plasma concentration. We conducted a retrospective multicenter study involving IPF patients from 13 French pediatric centers and a systematic review of literature-published cases. Eighteen patients were included in our case series, and thirty-four as literature review cases. The median age was 4.9 years and the diagnostic delay after the first signs of viral infection was 7 days. The lower limbs were involved in 49 (94%) patients with typical lesions. A recent history of VZV or HHV6 infection was present in 41 (78%) and 7 (14%) of cases, respectively. Most of the patients received heparin (n=51, 98%) and fresh frozen plasma transfusions (n=41, 79%); other treatment options were immunoglobulin infusion, platelet transfusion, corticosteroid therapy, plasmapheresis, and coagulation regulator concentrate infusion. The antithrombin level and platelet count at diagnosis appeared to be associated with severe complications. Given the rarity of this disease, the creation of a prospective international registry is required to consolidate these findings.

1003. Cytokine Levels in Sepsis and TNFα Association with Mortality but not Sepsis Severity or Infection Source: a Systematic Review and Meta-analysis

Background Sepsis is a global health problem associated with significant morbidity and mortality and is attributed to a “cytokine storm.”. However, anti-cytokine therapies have failed to lower sepsis mortality in clinical trials. Linking cytokine excess to sepsis pathogenesis requires quantification of cytokine levels in sepsis. This systematic review and meta-analysis characterizes levels of key cytokines in the circulation of sepsis patients and relates TNFα levels to mortality and patient characteristics. Methods Medline, Embase, Cochrane Library, and Web of Science Core Collection databases were searched from 1946 to May 2020 for studies in English disclosing cytokine levels in sepsis. Keywords included sepsis, septic shock, purpura fulminans, and tumor necrosis factor (TNF)α. We related cytokine amounts to 28-day mortality. Data analyses were performed using a random-effects model to estimate pooled odds ratios (OR) and 95% confidence intervals (CI). This systematic review is registered in PROSPERO under number CRD42020179800. Results A total of 3656 records were identified. After exclusions, 103 studies were included. Among these studies, 72 disclosed TNFα levels, 25 showed interleukin (IL)-1β levels, and 6 presented interferon (IFN)γ levels. The pooled estimate mean TNFα concentration in sepsis patients was 58.4 pg/ml (95% CI, 39.8-85.8 pg.ml; I2 = 99.4%). Pooled estimate means for IL-1α and IFNγ in sepsis patients were 21.8 pg/ml (95% CI, 12.6-37.8 pg.ml; I2 =99.8%) and 63.3 pg/ml (95% CI, 19.4-206.6 pg/ml; I2 = 99.7%), respectively. Elevated TNFα concentrations were associated with increased 28-day mortality (P=0.001). In a subgroup analysis, TNFα levels did not relate to sepsis source, sepsis severity, or sequential organ failure assessment (SOFA) score (figure 1). In a metaregression, TNFα associated with age, percentage of females and mortality at 28 days. Figure 1: A: TNFa levels according to sepsis source. B: TNFa levels according to measurement technique. C: TNFa levels according to presence or absence of cardiovascular disease. D: TNFa levels according to presence or absence of malignancy. E: TNFa levels according to sepsis severity. F: TNFa levels in fungal compared to other causes of sepsis (Yes=fungal sepsis; No= Other types of sepsis). G: TNFa levels according to SOFA score. H: TNFa levels and mortality at 28 days. Conclusion We presented levels of TNFα, IL-1β, and IFNγ in human sepsis and showed that TNFα elevations are associated with sepsis mortality. TNFα concentrations did not correlate with sepsis severity. We believe the concept that elevated cytokines cause sepsis should be revisited in the context of these data. Disclosures All Authors: No reported disclosures