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.