Discussion
Herein, we reported the case of a patient who presented a severe acute
renal failure secondary to granulomatous interstitial nephritis (GIN)
six months after the end of an r-CHOP treatment for mantle lymphoma.
GIN is a rare histological diagnosis that occurs in 0.5% to 0.9% of
biopsies [3]. It is associated with medication, infections,
sarcoidosis, crystallization, paraproteinemia, and Wegener’s
granulomatosis, and is also observed in idiopathic patterns [3].
Based on the overall clinical picture and the histological appearance of
the granulomas strongly suggestive of sarcoidosis, we retained an SLR in
the absence of evidence of systemic involvement of the granulomatous
infiltration,
SLR is characterized by the development of a granulomatous reaction that
is indistinguishable from sarcoidosis. Multiple drug classes have been
associated with SLR, which defines drug-induced sarcoidosis-like
reactions (DISRs) [4] and may affect a single organ such as the skin
or the spleen [5, 6].
The onset of DISRs is not necessarily concomitant with treatment and may
occur months after discontinuation of the drug [6].
Most reported medications can be classified as antiretroviral
combination therapies, tumor necrosis factor-α antagonists, interferons,
and immune checkpoint inhibitors [4].
The reported patient presented an SRL following CHOP and rituximab
therapy.
Limited literature described DISRs as an uncommon adverse effect of
rituximab when prescribed alone without chemotherapy [6, 7, 8] while
we did not find any study describing this adverse effect associated with
CHOP-based chemotherapy prescribed alone. This would incriminate
rituximab in the induction of the DISRs in patients who received an
r-CHOP protocol like our patient.
The temporal relationship between rituximab administration and SLR onset
in our patient supports the diagnosis of rituximab- DISRs. Indeed, B
cells that are targeted by rituximab play an important pathogenic role
in sarcoidosis [7, 9, 10].
Rituximab binds to CD20-positive B lymphocytes ranging from pre-B cells
to early plasmablasts, resulting in complete B-cell depletion 21 days
after infusion. Four to six months after that, rituximab clearance
occurs coinciding with a peripheral B cell repopulation which is higher
than before treatment, and the re-establishment of a naive B-cell pool
[9, 10]. Thus, our patient would have been early in the process of
repopulation of peripheral B cells at the time of SLR onset,
approximately six months after his last rituximab infusion.
London et al. [11] described the development of sarcoidosis in 39
patients treated for lymphoma (fourteen cases published for the first
time and 25 cases from a literature review). About one-third (13/39) of
these patients received rituximab, expressing concern about drug-induced
sarcoidosis associated with rituximab. The time from rituximab to the
onset of sarcoidosis was not reported in this study, but the median time
from the diagnosis of lymphoma to the diagnosis of sarcoidosis was 18
months. This ranged from just under three months to over 24 months.
Immunotherapy-DISRs are usually associated with airway and skin lesions.
Other clinical features include fever, extrathoracic lymph node
swelling, uveitis, hypercalcemia, nervous system, hepatic spleen, and
muscle and bone joint involvement [4]. The organs involved in the
study of London et al. were the lung and the lymph nodes. No kidney
involvement was described in the literature, meaning this is the first
reported case of renal SLR in the context of rituximab-DISRs.
The series of London et al. counted only seven cases of NLH and to the
best of our knowledge, it was not reported, after this study of SLR
associated with rituximab in patients with NHL and especially mantle
cells. The only study found in the literature focusing on mantle cell
lymphoma and sarcoidosis described a patient who developed mantle cell
lymphoma after several years of evolution of sarcoidosis [12].
The SLR responded well to oral corticosteroids at a dose of 1 mg/kg/d in
our patient. In the series by London et al., fourteen patients received
prednisone at a dose of 0.5 to 1 mg/kg/day with partial to complete
remission. Only two presented a relapse of the granulomatous
infiltration. Corticosteroids would be therefore an effective treatment
for this pathology.