Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ipilimumab is indicated for the treatment of melanoma in both the metastatic and adjuvant setting. Ipilimumab inhibits cytotoxic T-lymphocyte antigen 4, leading to the augmentation of T-cell activity and an antitumor immune system response. The side effect profile of ipilimumab consists of autoimmune-like events such as dermatitis, colitis, and thyroiditis. These immune-related adverse events can be serious, often resulting in the need for systemic immunosuppression with corticosteroids. We present a case of diffuse, nonnecrotizing granulomatous lymphadenitis and granulomatous vasculitis in a heavily pretreated patient with metastatic melanoma. After completion of 4 cycles of ipilimumab for the treatment of metastatic melanoma, our patient complained of increasing fatigue, drenching night sweats, and chills. Imaging revealed diffuse adenopathy involving several lymph nodes. Biopsy was positive for nonnecrotizing granulomatous lymphadenitis and granulomatous vasculitis. High-dose prednisone was initiated and tapered gradually over 6 weeks, resulting in complete resolution of the granulomatous disease.
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PMID:Case Report of Ipilimumab-Induced Diffuse, Nonnecrotizing Granulomatous Lymphadenitis and Granulomatous Vasculitis. 2927 30

Therapeutic blocking antibodies against programmed death 1 (PD1) and cytotoxic T-lymphocyte antigen 4 (CTLA4) are applied for advanced cancer therapy, but induce a wide range of immune-related adverse events. In our recent case of a 52-year-old female doctor suffering from breast cancer having metastasized to the lung and liver, it was decided to use nivolumab to prevent the disease progressing after excisional surgeries and multiple chemotherapies. One month after completing the nivolumab course, fatigue, hypoglycemia and hypotension developed and isolated ACTH deficiency (IAD) was diagnosed. A further month later, under steroid supplementation, hyperglycemia emerged alongside thirst and polydipsia, prompting a diagnosis of fulminant type 1 diabetes (FT1D). Her susceptibility to type 1 diabetes was examined by HLA haplotype and CTLA4 gene polymorphism analyses. Polymorphisms CT60G>A and +49G>A in CTLA4 both generated a GG genotype. Our patient manifested one of the rarest combinations of autoimmune disease induced by nivolumab. Whereas the HLA haplotype was unsusceptible to autoimmune type 1 diabetes, polymorphisms of CTLA4, the antibody of which frequently causes hypophysitis, were susceptible to FT1D. Peripheral modulation of activated T cells, mainly by PD-1 antibodies, induced FT1D associated with IAD in patients with CTLA4 polymorphism. This case reveals hints of the T-cell etiology in T1D and evidence of CTLA4 involvement in IAD.
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PMID:Fulminant type 1 diabetes associated with Isolated ACTH deficiency induced by anti-programmed cell death 1 antibody-insight into the pathogenesis of autoimmune endocrinopathy. 3081 40