Sivaprakasam Thabuna, Nitchaikulvatana Prachaya, Gedallovich Jodi, Shah Jagruti, Baker Matthew Charles
Department of Internal Medicine, University of South Dakota Sanford School of Medicine, Sioux Falls, SD, USA.
Department of Medicine, Division of Immunology and Rheumatology, Stanford University, Palo Alto, CA, USA.
BMC Rheumatol. 2025 Aug 1;9(1):95. doi: 10.1186/s41927-025-00548-1.
Immune checkpoint inhibitors (ICIs) have become a cornerstone in the treatment of metastatic melanoma. Several case reports have documented IgG4-related disease (IgG4-RD) as an adverse event following ICI therapy. Here we report the first instance of interstitial nephritis associated with IgG4-RD as an immune-related adverse event (irAE) following ICI treatment.
A 71-year-old male with malignant melanoma (BRAF wild-type) initially received one cycle of adjuvant pembrolizumab, followed by four cycles of ipilimumab/nivolumab after the occurrence of lung metastases. Four months later, a follow-up computed tomography (CT) revealed infiltrative masses in the kidneys, along with abnormal mediastinal and hilar lymphadenopathy but his baseline serum creatinine remained stable. A subsequent kidney biopsy showed renal parenchyma with significant interstitial nephritis and an increase in IgG4-positive plasma cells, with no evidence of malignancy. Plasma IgG4 levels were elevated at 294 mg/dL (normal 11-157 mg/dL), and complement C4 level was low at < 8 mg/dL. In addition, the patient had an asymptomatic rise in lipase (105 U/L, normal 7-60 U/L), but had no other findings to suggest pancreatitis. The patient was started on prednisone 40 mg daily with a plan to taper. A follow-up CT scan performed four weeks later showed near-complete resolution of the previously observed mediastinal lymphadenopathy and bilateral infiltrative renal masses.
This represents the first reported case of interstitial nephritis resulting from IgG4-related disease following ICI treatment. Clinicians should consider the potential for IgG4-RD, particularly with associated renal manifestations, in patients undergoing ICI therapy. Early recognition and treatment of this rare side effect can significantly impact the clinical outcome. This case highlights the importance of being vigilant for uncommon and new adverse effects following ICI treatment, especially as the field continues to evolve and new immunotherapies are developed.
Not applicable.
免疫检查点抑制剂（ICIs）已成为转移性黑色素瘤治疗的基石。几例病例报告记录了IgG4相关疾病（IgG4-RD）作为ICI治疗后的不良事件。在此，我们报告首例与IgG4-RD相关的间质性肾炎作为ICI治疗后的免疫相关不良事件（irAE）。
一名71岁男性，患有恶性黑色素瘤（BRAF野生型），最初接受了一个周期的辅助派姆单抗治疗，在出现肺转移后接着接受了四个周期的伊匹单抗/纳武单抗治疗。四个月后，随访计算机断层扫描（CT）显示双肾有浸润性肿块，同时纵隔和肺门淋巴结肿大异常，但他的基线血清肌酐保持稳定。随后的肾脏活检显示肾实质有明显的间质性肾炎，IgG4阳性浆细胞增多，无恶性证据。血浆IgG4水平升高至294mg/dL（正常范围11-157mg/dL），补体C4水平降低至<8mg/dL。此外，患者脂肪酶无症状升高（105U/L，正常范围7-60U/L），但无其他提示胰腺炎的表现。患者开始每日服用40mg泼尼松，并计划逐渐减量。四周后进行的随访CT扫描显示，先前观察到的纵隔淋巴结肿大和双侧浸润性肾肿块几乎完全消退。
这是首例报道的ICI治疗后由IgG4相关疾病导致的间质性肾炎病例。临床医生在接受ICI治疗的患者中应考虑IgG4-RD的可能性，尤其是伴有肾脏表现的情况。尽早识别和治疗这种罕见的副作用可显著影响临床结局。该病例凸显了对ICI治疗后罕见和新出现的不良反应保持警惕的重要性，特别是随着该领域不断发展和新的免疫疗法不断涌现。
不适用。
