clobetasol and Lung-Neoplasms

Immunotherapy has emerged as a highly effective treatment for numerous cancers. Use of checkpoint inhibitors against various molecules including programmed cell death protein-1 (PD-1), programmed death ligand-1 (PD-L1), and cytotoxic T-lymphocyte-associated protein-4 have become widespread in clinical practice. Compared with conventional chemotherapy, immunotherapy is associated with a unique set of immune reactions known collectively as immune-related adverse events (irAEs). Of known irAEs, cutaneous toxicity is among the most frequently observed in patients treated with immunotherapy. Although often mild, dermatologic toxicity can occasionally be high grade and potentially life-threatening. In this article, we report a case of PD-1 inhibitor-induced bullous pemphigoid-a serious adverse event that has been increasingly observed with use of PD-1/PD-L1 inhibitors. We will also review diagnosis and management of low-grade cutaneous irAEs and bullous disease with checkpoint inhibitors.. PD-1/PD-L1 inhibitor-induced bullous pemphigoid (BP) is a rare but potentially serious dermatologic toxicity associated with checkpoint inhibitorsIn patients with pruritus or rash that is refractory to topical steroids, physicians should have a greater index of suspicion for higher-grade cutaneous immune-related adverse events.There is no standardized treatment algorithm for management of PD-1/PD-L1 inhibitor-induced BP, but patients frequently require topical and systemic steroids.

Topics: Aged; Antineoplastic Agents, Immunological; B7-H1 Antigen; Carcinoma, Non-Small-Cell Lung; Clobetasol; Female; Humans; Immunotherapy; Lung Neoplasms; Nivolumab; Pemphigoid, Bullous; Prednisone; Programmed Cell Death 1 Receptor; Skin

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Clobetasol; Edema; Exanthema; Glucocorticoids; Humans; Leg; Lung Neoplasms; Male; Pemetrexed; Prednisolone; Treatment Outcome

The increased use of monoclonal antibodies that target the immune checkpoint T cell receptor programmed death-1 (PD1) to treat numerous solid tumors has led to several reports describing associated cutaneous adverse events. Although lichenoid reactions have been well described, we propose that PD1 inhibitor-induced inverse lichenoid eruption (PILE) is a distinct variant. We describe two patients who presented with nearly identical deeply erythematous, malodorous, eroded anogenital plaques with focal crusting. Diagnosis of PILE was established given the biopsy findings and temporal association with PD1 inhibitor therapy. Treatment with clobetasol ointment was successful without necessitating discontinuation of immunotherapy. The findings were consistent with the only other previously published case of inverse lichenoid eruption in the groin secondary to PD1 inhibitors.

Topics: Abdomen; Adenocarcinoma; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Buttocks; Clobetasol; Female; Glucocorticoids; Humans; Lichenoid Eruptions; Lung Neoplasms; Middle Aged; Ointments; Perineum; Programmed Cell Death 1 Receptor; Skin

The Kelch-like ECH-associated protein 1 (KEAP1)-nuclear factor E2-related factor 2 (NRF2)pathway has a central role in cellular antioxidant defense. NRF2 activation due to KEAP1 or NRF2 mutations occurs frequently in many cancers, suggesting that NRF2 inhibition could be a promising therapeutic strategy. However, no potent NRF2 inhibitors are clinically available to date. To develop potent NRF2 inhibitors for therapeutic purpose, we screened ~4000 clinical compounds and determined clobetasol propionate (CP) as the most potent NRF2 inhibitor. Mechanistically, CP prevented nuclear accumulation and promoted β-TrCP-dependent degradation of NRF2 in a glucocorticoid receptor- and a glycogen synthase kinase 3 (GSK3)-dependent manner. As a result, CP induced oxidative stress and strongly suppressed the anchorage-independent growth of tumors with KEAP1 mutation, but not with the wild-type KEAP1. Further, CP alone or in combination with rapamycin strongly inhibited the in vitro and in vivo growth of tumors harboring mutations in KEAP1 or both KEAP1 and LKB1 that are frequently observed in lung cancer. Thus, CP could be a repurposed therapeutic agent for cancers with high NRF2 activity. We also proposed that the use CP and rapamycin in combination could be a potential therapeutic strategy for tumors harboring both KEAP1 and LKB1 mutations.

Topics: Animals; Anti-Inflammatory Agents; Cell Line, Tumor; Clobetasol; Drug Screening Assays, Antitumor; Humans; Kelch-Like ECH-Associated Protein 1; Lung Neoplasms; Mice, Inbred BALB C; Mice, Nude; NF-E2-Related Factor 2; Random Allocation; Signal Transduction; Xenograft Model Antitumor Assays

Wells syndrome (WS) or eosinophilic cellulitis is a rare, idiopathic, inflammatory dermatosis. The typical clinical presentation is urticarial plaque without preferential location that usually heals without scarring. We present a 62-year-old man with history of lung cancer that had undergone a right superior lobectomy 12 months previously. The patient had a relapsing dermatosis beginning about 6 months before the diagnosis of the lung cancer, characterised by pruritic, erythematous plaques located on the trunk and arms. These lesions spontaneously resolved within a few weeks without scarring. A skin biopsy revealed findings compatible with WS. Several diseases have been associated with WS. These include haematological diseases, fungal, parasitic and viral infections, drug reactions and rarely non-haematological malignancies. We present a case of this rare syndrome in a patient with history of lung cancer that we believe acted as a triggering event. To our knowledge, this is the second case reporting this association.

Topics: Administration, Topical; Biopsy; Cellulitis; Clobetasol; Dermatologic Agents; Eosinophilia; Humans; Loratadine; Lung Neoplasms; Male; Middle Aged; Recurrence; Skin Diseases; Tacrolimus; Treatment Outcome

Sorafenib is a new drug, multikinase inhibitor, which has been recently approved for the treatment of metastatic renal cell carcinoma and hepatocellular carcinoma. Up to 90 percent of patients receiving this drug have been reported to develop dermatological symptoms. Recently, it has been suggested that the appearance of skin toxicity during therapy may indicate antitumor activity. We report a new case of sorafenib-induced severe hand-foot skin reaction, which hindered the patient's normal life. The reaction was successfully treated with topical costicosteroids and discontinuation of sorafenib. However, the patient died one month later.

Topics: Antineoplastic Agents; Benzenesulfonates; Bone Neoplasms; Carcinoma, Hepatocellular; Clobetasol; Disease Progression; Drug Eruptions; Fatal Outcome; Foot Dermatoses; Hand Dermatoses; Humans; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Niacinamide; Phenylurea Compounds; Protein Kinase Inhibitors; Pyridines; Sorafenib