Discussion
Tocilizumab has been associated with both atypical and delayed
presentations of infections.5 Atypical presentations
of common conditions in patients on tocilizumab include case reports of
pneumonia with absence of fever and disproportionately normal or mildly
elevated biochemical markers.5 Delayed presentations
of severe infection have also been reported in patients on tocilizumab,
with case reports of disseminated Staphylococcus aureusbacteraemia associated with epidural abscess, polyarticular septic
arthritis, and empyema.4 Other unusual presentations
include re-activation of latent tuberculosis presenting as fulminant
sepsis with splenic abscess two weeks after initiating
tocilizumab.6 An increased risk of fungal
co-infections and reports of invasive fungal disease have also been
observed in patients after a single dose of tocilizumab for the
management of COVID-19.7,8
We present a case of Staphylococcus aureus subcapsular splenic
abscess and associated left-sided empyema in the setting of tocilizumab.
Using “tocilizumab” and “splenic abscess” search terms on PubMed and
Google Scholar, there was a single case report of splenic abscess in
context of reactivated tuberculosis.6 There were no
previously reported cases of non-mycobacterial splenic abscess
associated with tocilizumab therapy, and hence this would be the first
reported case to the best of our knowledge.
In this clinical case, we hypothesise the formation of splenic abscess
was by haematogenous seeding from transient but uncapturedStaphylococcus aureus bacteraemia in the context of antibiotic
therapy suppression, with the recurrent Bartholin cyst infection being
the likely primary source of infection. The left sided empyema/pleural
effusion with biopsy-proven pleural infection, was likely a continuation
of the adjacent splenic abscess Staphylococcus infection through
the presence of otherwise clinically-insignificant congenital
diaphragmatic defects,9 given the similar radiological
appearance (Figure 1). While the rotational injury of the spine which
prompted the patient’s presentation may have coincidentally caused
concurrent musculoskeletal pain in her left upper quadrant and flank, it
is likely to be a red herring in the setting of the splenic abscess
being the more plausible cause for progressively worsening pain. The
significant immunosuppressive regimen of leflunomide, methotrexate and
tocilizumab likely contributed to the development of the atypical
infection and delayed presentation, due to the patient having a markedly
suppressed ability to mount an immune response and hence remaining
relatively asymptomatic during the early stages of infection. However,
we postulate that this atypical presentation was in particular due to
the recent commencement of tocilizumab – given the patient had
previously tolerated methotrexate and leflunomide for two years prior
without developing significant infections.
This case emphasises the importance of considering infection as a
differential diagnosis for common presentations such as suspected
musculoskeletal pain in patients who are on tocilizumab. Additionally,
given tocilizumab inhibits IL-6 mediated production of
CRP,5 a normal CRP may be unreliable for excluding
infection. Conversely, elevation in CRP in the setting of active
tocilizumab therapy may be a marker of severe disseminated infection –
as exemplified by the present case. As the availability and use of
tocilizumab increases, it is increasingly important for clinicians to
have a high index of suspicion for delayed presentations of unusual
infections in patients on tocilizumab therapy, including those who
present with otherwise common presentations such as suspected
musculoskeletal pain.