In asplenic and/or immunodepressed patients, the infection caused by C. canimorsus can determinate a Waterhouse-Friderichsen Syndrome evolving in a MODS [4]. The clinical course is characterized by a septic shock complicated by a DIC that is responsible of the diffuse microvascular thromboses accounting for (a) the rapidly extending skin infarctions 9; (b) the occurrence of HBD and AKI; and (c) the adrenal failure caused by the plugging of the adrenal venules draining the medullary sinusoids and the subsequent increase of the venous pressure leading to the intraglandular hemorrhage. The rapid deterioration of the clinical conditions alongside with the widespread involvement of the skin account for the denomination of “purpura fulminans” (PF) that is often used as a synonymous of the syndrome [9–14]. The underlying causes are not fully understood, and include (a) the capsular polysaccharide that affect the host-pathogen interaction by blocking the complement and the phagocytosis; (b) the presence of catalase making them resistant to the H2O2 produced by the macrophages; and (c), in asplenic subjects, the lack of an adequate number of B1a cells due to the absence of the splenic marginal zone B [10].
In our patient, although the cultures remained negative after three weeks of incubation, the MALS can be likely ascribed to a C. canimorsus infection due to the asplenia, the recent dog bite, the stormy course and the gram- bacilli visible inside the neutrophils that were identical to those described in other cases of septic shock due to same organism [14]: thus, is conceivable that this finding could be ascribed either to the antibiotic treatment initiated some days before the ICU admission and/or to the use of a medium not allowing the growth of this germ [15].
Actually, in ours as in other cases of C. canimorsus-related septic shock, the MODS was determined by the highly prothrombotic DIC: although the trigger(s) are not precisely identified due to the unusual occurrence of this infection, is has been hypothesized that the pathogen adhesion to the endothelium causes the upregulation of adhesion molecules and the margination of polimorphonucleates whose proteases impairs the endothelial thrombomodulin, that, in turn, substantially decreases the function of the Proteins C (PC). This is the same mechanism occurring in patients with meningococcal PF [16, 17].
AS different circumstances account for the poor outcome occurred in ours as well in other patients with MALS due to C.canimorsus, some considerations for the treatment are warranted.
First, our patient presented a full-blown MODS already at the admission; then, since most of the treatments indicated in the Surviving Sepsis Campaign are time-dependent, they could hardly modify the clinical course in an advanced phase of the disease. Consequently, patients with known risk factors for septic shock due to C.canimorsus should be encouraged to seek immediate medical advice in the event of a pet bite.
Second, the high mortality of C.canimorsus-associated MALS can be ascribed more to the occurrence of DIC than to the infection by itself; consequently, measures aiming to restore the anticoagulant capabilities, including the administration of FFP and AT III should be adopted; the administration of PC zymogen concentrates could be considered but the reduced or absent levels of thrombomodulin might prevent its activation.
Third, the extremely elevated CK despite the presence of peripheral pulses values likely indicates a diffuse muscle necrosis due to the DIC-associated plugging of the microvascular network despite the presence of peripheral pulses [18] it is arguable that had the patients survived, multiple amputations would have been required.
Finally, as it appears that most patients C. canimorsus septic shock fail to respond to the current treatments, other approaches are required to abate the hyperinflammatory reaction that is the primer of the DIC; recently, Shakoory et al [19] rewieved the results of a trial in which septic shock patients were given a blocker of the Interleukin-1 cellular receptor and demonstrated that only patients with MALS took advantage of this treatment; moreover, similar positive effects of Anakinra and of the Il-6 inhibitor tocilizumab have been reported also in different trials involving critical patients with severe Covid-19 pneumonia [20]. Then, the early off-label use of these substances could be valuable in patients with severe C. canimorsus infections possibly in association with HP and/or other blood purification techniques.
In our patient, all the therapeutic options that included both current and adjunctive treatment of septic shock failed to influence the clinical course likely due to the advanced phase of the disease. Patients with known risk factors for C. canimorsus infection and subsequent complications should not be discharged home but admitted to the hospital for a closer clinical survey and a prompt referral to the ICU.