A Retrospective, Single-Institution Experience of Bullous Pemphigoid as an Adverse Effect of Immune Checkpoint Inhibitors

Abstract

Immune checkpoint inhibitors are a class of cancer treatment drugs that stimulate the immune system’s ability to fight tumor cells. These drugs are monoclonal antibodies targeting im-mune-inhibiting proteins on cancer cells, such as CTLA-4 and PD-1/PD-L1. Immune checkpoint inhibitors cause many immune-related adverse events. Cutaneous toxicities are of the most common adverse effects and occur with a range of severity. Bullous Pemphigoid is a rare adverse event with a high impact on quality of life that may occur after immune checkpoint inhibitor treatment. In this article, we investigate current research on immune checkpoint inhibitors, cutaneous adverse events, and common presentations and treatments, with a specific focus on Bullous Pemphigoid, its characteristics, onset timing, and treatment. Significant findings include a negative skew in the onset of presentation. Furthermore, we describe exclusive cases.

Long-Lasting Therapeutic Response following Treatment with Pembrolizumab in Patients with Non-Small Cell Lung Cancer: A Real-World Experience

“…Pembrolizumab is currently one of the most promising checkpoint inhibitor immunotherapies. Pembrolizumab is a humanized IgG4 monoclonal antibody targeting PD-1 [ 11 ], which is used as monotherapy vs. chemotherapy and in combination with chemotherapy vs. chemotherapy alone for treating metastatic NSCLC [ 12 , 13 , 14 , 15 ].…”

Unexpected Adverse Events of Immune Checkpoint Inhibitors

“…The irAEs due to pembrolizumab include hypo-or hyperthyroidism, constipation, diarrhea, fever, cough, fatigue, rash, pruritus and, in some cases, musculoskeletal pain (Table 1) [2,4,13,14]. Abbreviations: RCC, renal cell carcinoma; CRC, colorectal cancer; HCC, hepatocellular carcinoma; NSCLC, non-small-cell lung cancer; SCC, squamous cell carcinoma; MSI, microsatellite instability; MMR, mismatch repair; HNSCC, head and neck squamous cell carcinoma; SCLC, small-cell lung cancer; UTIs, urinary tract infections; ICI, immune checkpoint inhibitors; PD-1, programmed cell-death 1; PDL-1, programmed death-ligand 1.…”

Carpal Tunnel Syndrome Associated with Immune Checkpoint Inhibitors

“…CTLA-4 (CD152), a member of the B7/CD28 family, facilitates immunosuppression by indirectly inhibiting signaling via the CD28 costimulatory receptor. Its higher affinity for CD80 (B7-1) and CD86 (B7-2) results in competitive inhibition of CD28 costimulation during T cell priming, reducing the release of proinflammatory cytokines like IL-12 and cytotoxic enzymes such as perforin and granzyme B [ 13 , 14 , 28 , 29 , 30 , 31 ]. CTLA-4 also mediates the endocytosis of CD80 and CD86 on antigen-presenting cells (APCs), reducing their availability for CD28.…”

“…Such potentially life-threatening events may include drug rash with eosinophilia, toxic epidermal necrolysis, systemic symptoms, as well as Stevens–Johnson syndrome, and acute generalized exanthematous pustulosis ( Table 1 ). Atezolizumab has not been previously reported to be associated with CTS [ 13 , 14 , 38 ].…”

“…The effectiveness of ICIs lies in their ability to target immune checkpoints and disrupt the mechanisms that cancer cells utilize to evade immune recognition and targeted programmed cell death. By blocking transmembrane receptors of the immune checkpoint apparatus, including cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), programmed cell death protein (PD-1), and its ligand (PD-L1), ICIs unleash the adaptive cellular immune system, enabling it to mount a robust and sustained anti-tumor response [ 13 , 14 ]. However, adverse events characteristic of autoimmunity were initially documented in animal models secondary to the immune checkpoint blockade [ 15 , 16 ].…”