NS, not significant; NA, not available; IVIG, intravenous
immunoglobulin; UC, ulcerative colitis; SARS-CoV-2, severe acute
respiratory syndrome coronavirus 2; IL, interleukin; M, male; F, female
The ages of the patients in these cases ranged from 22 to 65 years, and
they had few comorbidities. All patients had new-onset adult-onset
Still’s disease, which was treated using NSAIDs, steroids, tocilizumab,
anakinra, and intravenous immunoglobulin. All the patients recovered
after treatment. Some hyperinflammatory responses after vaccination can
be self-limiting; however, cases similar to those listed in Table 1,
wherein the symptoms meet the classification criteria for adult-onset
Still’s disease and improve after treatment, should be carefully
assessed without dismissing the symptoms as simple side effects of the
SARS-CoV-2 vaccine. In addition, patients should be appropriately
notified when a diagnosis is made.
The symptoms of adult-onset Still’s disease in the reported cases
generally started three weeks after vaccination. To our knowledge, the
present case is the first reported case of a patient with ulcerative
colitis who developed adult-onset Still’s disease after SARS-CoV-2
vaccination and was treated using an NSAID alone. The distinguishing
characteristics of the present case are the presence of ulcerative
colitis as a comorbidity and the positive response to NSAID treatment
even with extremely high levels of IL-18, which is suggested to be an
inflammatory marker of adult-onset Still’s disease2and is correlated to the severity of active adult-onset Still’s
disease.18 Patients with adult-onset Still’s disease
show extremely high IL-18 levels compared with patients with other
inflammatory diseases.18 Sequential measurement of
IL-18 level may be useful in guiding treatment as it can reflect disease
activity in adult-onset Still’s disease.19 A clinical
practice guideline suggests that IL-18 level in addition to ferritin and
C-reactive protein levels can be used to evaluate the extent of
inflammation in Still’s disease.20 The guideline also
indicates that NSAIDs can be used in addition to the mainstay treatment
comprising systemic steroids, which can be used to alleviate symptoms
with mild adult-onset Still’s disease.20
In the present case, the positive response to NSAID treatment in the
presence of high IL-18 levels after SARS-CoV-2 vaccination supports the
diagnosis of adult-onset Still’s disease. The involvement of
inflammatory cytokines, which can be induced by post-vaccination
new-onset adult-onset Still’s disease or adult-onset Still’s disease
flares, may imply that the common background etiology includes
inflammasomes and hyperinflammation through macrophage activation and
proinflammatory cytokines, such as IL-6, IL-18, and tumor necrosis
factor.
Adult-onset Still’s disease is a rare comorbidity in patients with
ulcerative colitis. Only one case of Crohn’s disease with adult-onset
Still’s disease has been reported.4 Multifactorial
factors that are likely relevant to the coexistence of adult-onset
Still’s disease and inflammatory bowel disease include intestinal
microbiota, mucosal barrier, genetic susceptibility, and environmental
factors; however, no definitive etiology has yet been
clarified.21 Although ulcerative colitis can present
with extraintestinal symptoms involving the skin and joints that can be
similar to the presentation of adult-onset Still’s disease, the rarity
of the coexistence of the two diseases suggests the independence of
their pathologies. Nevertheless, the present case indicates that even
though the coexistence of ulcerative colitis and adult-onset Still’s
disease is rare, SARS-CoV-2 vaccines may trigger a specific inflammatory
process in patients with ulcerative colitis. The patient’s
hyperinflammatory status suppressed by salazosulfapyridine may have been
substituted by an autoinflammatory condition triggered by SARS-CoV-2
vaccination.
In conclusion, this is the first report of the occurrence of adult-onset
Still’s disease in a patient with ulcerative colitis. The possibility of
autoinflammatory conditions such as adult-onset Still’s disease should
be considered when evaluating or treating symptoms suspected to be side
effects of SARS-CoV-2 vaccination, regardless of the comorbidities
associated with such symptoms.
AUTHOR CONTRIBUTIONS
Takahiro Kobayashi : Conceptualization; data curation; project
administration; writing-original draft. Kenichi Hashimoto :
Project administration; supervision; writing-review and editing.Yasuyoshi Kusanagi: Supervision; writing-review and editing.Yuji Tanaka: Supervision; writing-review and editing.
ACKNOWLEDGMENTS
This work was supported by the Fukuda Foundation for Medical Technology
(2019). We thank Editage for providing professional English editing of
the manuscript.
ORCID
Kenichi Hashimoto https://orcid.org.
0000-0001-6838-1215
Takahiro Kobayashi https://orcid.org.
0000-0002-9932-2987
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FIGURE CAPTIONS
FIGURE 1 (A) Salmon pink rashes with scratch dermatitis on the lower
left leg. (B) Skin at three months following treatment.
FIGURE 2 Clinical course of the case, including data on the patient’s
body temperature, laboratory data, and treatment. CTRX, ceftriaxone; BT,
body temperature; CRP, C-reactive protein; IL, interleukin.