Received: 3 March 2021 Revised: 7 March 2021 Accepted: 8 March 2021
DOI: 10.1111/nep.13870
CORRESPONDENCE
Takayasu's arteritis in a girl with steroid-dependent nephrotic
syndrome: Could rituximab be the culprit?
Rituximab (RTX), an anti-CD20 chimeric monoclonal antibody, is
used for the treatment of steroid-dependent nephrotic syndrome
(SDNS).1 Although RTX is relatively safe,1 RTX-induced adverse
events, including inflammatory bowel diseases (IBD) and paradoxi-
2-5
cal cutaneous vasculitis, have been reported. However, RTX-
associated Takayasu's arteritis (TA) has not been reported. Here,
we report a case of TA following RTX administration for the treat-
ment of SDNS.
A 14-year-old Japanese girl with long-standing SDNS devel-
oped remittent fever, abdominal pain, and weight loss. She had
been suffering from SDNS since the age of 1 year and had
received a combination of prednisolone (PDN) and immunosup-
pressants (mizoribine, then cyclosporine A, and finally
tacrolimus). A percutaneous renal biopsy performed at 3 years
showed minor glomerular abnormalities. Because of the difficult
clinical course, administration of a single dose of RTX, 500 mg
2
(350 mg/m ), every 6 months was commenced, when she
was12 years old. Her serum creatine was 0.39 mg/dl. The num-
ber of circulating CD19- and CD20-positive B cells reduced dras-
tically within a month after RTX administration. PDN dose was
reduced to 5 mg on alternate days without relapse of SDNS.
However, 3 months after receiving the fourth dose of RTX, the
patient developed malaise and weight loss. B cells remained
depressed, and proteinuria was negative. No signs of IBD were
2,3
noted. Left cervical vascular murmur and non-specific inflam-
matory reactions (increased level of serum C-reactive protein,
9.1 mg/dl; erythrocyte sedimentation rate, 94 mm/h) led us to
perform whole-body positron emission tomography that showed
F I G U R E 1 Accumulation of 18F-fluorodeoxyglucose (maximum standardised uptake value 5.5) on the wall of the left common carotid artery
suggesting inflammatory changes (left panel); Accumulation of 18F-fluorodeoxyglucose (maximum standardised uptake value 4.2) was also
apparent in the superior mesenteric artery (right panel)
Nephrology. 2021;1–2. wileyonlinelibrary.com/journal/nep
18
accumulation of F-fluorodeoxyglucose in the left common
carotid artery, superior mesenteric artery, and thoracic aorta
(Figure 1). Further, magnetic resonance imaging showed a high
signal area in the left common carotid artery. Therefore, a provi-
sional diagnosis of TA was made. Human leukocyte antigen
(HLA) testing revealed B52 positivity. After the diagnosis of TA,
the patient was successfully treated with increased dose of PDN
combined with tocilizumab (TCZ), an anti-human interleukin-6
receptor monoclonal antibody. At present, she is, now 17 years
old, receiving low-dose PDN, tacrolimus and intravenous TCZ
(once a month).
A protective effect of CD20-positive B cells in the gut has been
reported; therefore, their depletion sometimes triggers the onset of
IBD.2,3 Alternatively, RTX-mediated immunocomplexes with
degraded B cells components play a role in triggering systemic vas-
culitis.4,5 Even though, development of TA after RTX administration
may have been a coincidence, considering her clinical course, we
speculate that RTX, at least in part, may have played a role in the
late onset of TA. Physicians should be aware of late-onset systemic
vasculitis associated with RTX administration, especially in patients
with HLA B52 positivity.
CONFLIC T OF INT ER E ST
The authors declare no potential conflict of interest.
Azusa Sugita1
Shun Hashimoto1
Riko Sato1
© 2021 Asian Pacific Society of Nephrology 1
2 CORRESPONDENCE
Masahi Fujita1
Shojiro Watanabe1
1
Tomomi Aizawa
Koji Tsugawa1
Hiroshi Tanaka1,2
1
Department of Pediatrics, Hirosaki University Hospital, Hirosaki, Japan
2
Department of School Health Science, Hirosaki University Faculty of
Education, Hirosaki, Japan
Correspondence
Hiroshi Tanaka, Department of School Health Science, Hirosaki
University Faculty of Education, 1 Bunkyo-cho, Hirosaki 036-8224,
Japan.
Email: hirotana@hirosaki-u.ac.jp
OR CID
Shojiro Watanabe https://orcid.org/0000-0002-4379-5857
Tomomi Aizawa https://orcid.org/0000-0002-1425-1017
Hiroshi Tanaka https://orcid.org/0000-0001-7057-813X
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