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.