A 44-Year-Old Female With Overwhelming Sepsis

sepsis, asplenia, RPSA gene, Howell-Jolly bodies, Streptococcus pneumonia

To the Editor—The case presented as a photo quiz by Meléndez-Carmona et al is described as fatal pneumococcal sepsis presenting as purpura fulminans in a previously healthy asplenic 44 year-old woman [1, 2]. But it can also be considered as isolated congenital asplenia (ICA). The name difference is significant because it raises the possibility of a congenital, and therefore probably inherited, defect. Inborn errors have been discovered in patients with ICA [3]. More than half of the patients have mutations in the RPSA gene, which encodes a ribosomal protein. Our initial studies indicated that ICA is transmitted as an autosomal dominant trait with complete penetrance. Everyone who had a mutation affecting the coding region of RPSA lacked a spleen. However, our current work indicates that with some mutations, especially outside the coding region, penetrance is incomplete [4].

The diagnosis of ICA is based on the absence of a detectable spleen by ultrasound (US) or computed tomography (CT) scan, the presence of Howell-Jolly bodies on a peripheral blood smear, and the absence of a congenital heart abnormality or a splenectomy. Invasive, life-threatening infections are common [5]. Streptococcus pneumoniae was the infecting organism in 15 of the 24 ICA cases in which the causative organism was known [6]. Haemophilus influenzae caused 6 infections. Interestingly, no cases had Neisseria meningitidis, a virulent encapsulated bacterium isolated as the third most common organism from splenectomized patients [7]. Although severe sepsis usually appears in infancy or childhood, the first episode of septicemia in a woman with ICA occurred at age 60 [8].

Recommendations for patients with ICA include prophylactic antibiotics, vaccination to prevent pyogenic infections, and prompt antibiotic treatment in case of suspicion of infection. Their families should have genetic counseling. Although vaccination is less effective in asplenic patients and some of the serotypes of S. pneumoniae causing infections in ICA patients are not in the vaccine, vaccination with the pneumococcal vaccines (both Prevnar and Pneumovax) and Haemophilus B vaccine are strongly recommended (https://www.cdc.gov/vaccines/adults/rec-vac/health-conditions/asplenia.html). The usual vaccinations to prevent other infectious diseases should also be given. Recommendations for antibiotic prophylaxis vary from 5 years of age (https://www.cdc.gov/pneumococcal/clinicians/prevention.html) to lifetime [9]. Individuals with ICA should report promptly for emergent evaluation at the onset of symptoms.

In the photo quiz, the patient was considered to have a normal abdominal US 1 year previously. Since in the absence of splenectomy, the spleen is not known to disappear so quickly, the previous US should be reviewed to see if it confirms the absence of a spleen indicated by abdominal CT. An unlikely alternative is that asplenia occurred due to an autoimmune mechanism [10]. As the patient had no autoimmune manifestations, we think it more likely that the patient had ICA. The patient’s family should be contacted, and at least an examination for Howell-Jolly bodies should be performed. If they are present, abdominal US or CT should be performed and the DNA from relevant family members sequenced to detect variations in RPSA.

Notes

Funding. This work was supported by the March of Dimes Foundation (no. 1-FY12-440), St. Giles Foundation, National Center for Research Resources and the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH) (no. 8UL1 TR001866)

Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.