Checkpoint inhibitor-associated drug reaction with eosinophilia and systemic symptom syndrome.

Drug reaction with eosinophilia and systemic symptom syndrome is a potentially fatal drug reaction that must be recognized quickly. Ipilimumab and nivolumab are both important agents in the treatment of melanoma and continue to be studied in other malignancies. We believe the mainstay of therapy for immunotherapy-induced drug reaction with eosinophilia and systemic symptom syndrome is early recognition, discontinuation of the inciting agent, supportive care, and treatment with high dose corticosteroids with appropriate tapers that may reduce the length of internal organ injury in cases with liver or kidney involvement.

New-onset toxicity with programmed death-1 inhibitor rechallenge.

Immunotherapy has become a mainstay in the treatment of metastatic melanoma. Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) inhibitors and programmed death-1 (PD-1) inhibitors, which have been added more recently, represent two of the main classes of immunomodulating agents. PD-1 inhibitors are well tolerated and are known to have a decreased rate of occurrence of adverse effects compared with CTLA-4 inhibitors. However, the risk remains for serious immune-mediated adverse reactions. Given their long half and extended efficacy, treatment with a CTLA-4 inhibitor before use of a PD-1 inhibitor may increase the risk of adverse effects. In addition, caution should be exercised when rechallenging grade 3 or 4 adverse effects with the same agent or a different agent of the same class. The re-emergence of a previous toxicity may occur or, as found in this case, a new severe effect may arise. This article will present a case of fatal immune-related hepatoxicity in a patient treated with a CTLA-4 inhibitor, followed by treatment with a PD-1 inhibitor. The mechanisms of action and safety profiles for both classes of drugs will also be reviewed.

Docetaxel/Cyclophosphamide-Induced Phototherapy Recall.

Phototherapy recall can occur unexpectedly as a result of treatment with commonly used medications and chemotherapy. These reactions are rare. The recall reaction is an inflammatory response that is triggered by many medications. Cyclophosphamide and docetaxel are widely used chemotherapeutic agents that are useful in the management of many different malignancies. The pathophysiology of phototherapy recall is not clearly understood. This case highlights the need for practitioners to be aware of this potential reaction, even though UV exposure may have occurred in the distant past. We present, to the best of our knowledge, the first phototherapy recall dermatitis that occurred years after UV exposure induced by cyclophosphamide and docetaxel. The frequency of administration of this drug and the profound implications of this adverse effect make this case an important contribution to the medical literature.

Delayed dermatologic hypersensitivity reaction secondary to ipilimumab.

The treatment of melanoma has long favored the use of immunologic agents. Ipilimumab is a monoclonal antibody used to enhance the immune response. This therapy is associated with a variety of adverse reactions including skin reactions. Although dermatologic toxicities associated with the use of ipilimumab are common, delayed hypersensitivity reactions related to the drug have yet to be identified. This report is believed to be the first case of a delayed, severe dermatologic drug-related reaction secondary to ipilimumab. This case highlights the potential for severe toxicity for long periods after administration of ipilimumab.

Cumulative dermatologic toxicity with ipilimumab and vemurafenib responsive to corticosteroids.

Dermatologic toxicity is a known reaction of ipilimumab and vemurafenib. Because of the lack of effective treatments and aggressive nature of melanoma, treatments are often discontinued and new treatments are initiated in rapid succession. We report what we believe to be the first case of cumulative dermatologic toxicity secondary to rapid-sequential treatment with ipilimumab and vemurafenib for metastatic melanoma that responded to high-dose steroids. This case highlights the combined toxicity of these two drugs that can occur as a result of overlapping toxicity. It also illustrates the need for a substantial wash out period between rapid cycling of these two drugs secondary to ipilimumab's long half-life.