Stevens-Johnson syndrome like eruptions; perforated duodenal ulcer; sepsis; multiple small oral ulcers; fatigue; oral mucositis; tongue ulcer; difficulty swallowing; a non-pruritic and non-tender rash in the upper back and upper extremities; lip ulcer; hemorrhagic crust more prominent in the lower lip, showing cracking and fissuring with blood encrustation; hemorrhagic crust more prominent in the lower lip, showing cracking and fissuring with blood encrustation; extensive vesicles/vesicles with erythematous borders scattered in hard palate, mucosa, and gums; lip, showing cracking and fissuring; vesicles with erythematous borders scattered in hard palate, mucosa, and gums; death NOS; This case was reported in a literature article and described the occurrence of unknown cause of death in a 80-year-old female patient who received Herpes zoster (Herpes Zoster vaccine) for prophylaxis.  Co-suspect products included pembrolizumab for adenocarcinoma lung.   Previously administered products included chemotherapy, pembrolizumab (5 doses received on an unspecified date) and immunotherapy. Concurrent medical conditions included adenocarcinoma lung (treated with lobectomy).   On an unknown date, the patient received the 1st dose of Herpes Zoster vaccine and pembrolizumab at an unknown dose and frequency. On an unknown date, unknown after receiving Herpes Zoster vaccine, the patient experienced unknown cause of death (serious criteria death and GSK medically significant), stevens johnson type reaction (serious criteria hospitalization and GSK medically significant), duodenal ulcer perforation (serious criteria hospitalization and GSK medically significant), sepsis (serious criteria hospitalization and GSK medically significant), mouth ulcer (serious criteria hospitalization), fatigue (serious criteria hospitalization), mucositis oral (serious criteria hospitalization), tongue ulceration (serious criteria hospitalization), swallowing difficult (serious criteria hospitalization), rash (serious criteria hospitalization), lip ulcer (serious criteria hospitalization), lip hemorrhage (serious criteria hospitalization), crust (serious criteria hospitalization), vesicles (serious criteria hospitalization), cracked lips (serious criteria hospitalization) and erythema (serious criteria hospitalization). The patient was treated with acyclovir, prednisone and antiseptics (nos) (Antiseptic). Pembrolizumab was discontinued. On an unknown date, the outcome of the unknown cause of death was fatal and the outcome of the stevens johnson type reaction was recovering/resolving and the outcome of the duodenal ulcer perforation, sepsis, mouth ulcer, fatigue, mucositis oral, tongue ulceration, swallowing difficult, rash, lip ulcer, lip hemorrhage, crust, vesicles, cracked lips and erythema were unknown. The reported cause of death was unknown cause of death.   The reporter considered the unknown cause of death, stevens johnson type reaction, duodenal ulcer perforation, sepsis, mouth ulcer, fatigue, mucositis oral, tongue ulceration, swallowing difficult, rash, lip ulcer, lip hemorrhage, crust, vesicles, cracked lips and erythema to be related to Herpes Zoster vaccine.   Additional details were provided as follows: This case was reported in a literature article and described the occurrence of Stevens-Johnson syndrome (SJS) like eruptions in an 80-year-old female patient, who was vaccinated with unspecified recombinant zoster vaccine (RZV) (manufacturer unknown) for prophylaxis. The patient was woman. The patient had a 13-year history of lung adenocarcinoma. The patient was treated with lobectomy. Despite several surgeries and chemotherapy, progression to advanced lung adenocarcinoma with invasion of the visceral pleura occurred. Based on biomarker testing (PD-L1 positive, EGFR/ALK negative), 15 weeks before the presentation, the patient received immunotherapy with a single-agent pembrolizumab that resulted in improvement of disease progression. There were no other new medications recorded either previous experience with other immunotherapy agents or corticosteroids. No information on patient's family history was provided. On an unspecified date, the patient received 1st dose of unspecified recombinant zoster vaccine (RZV) (administration route and site unspecified, dosage unknown; batch number not provided). The age of vaccination was not provided but it could be 79 years or 80 years. On an unspecified date, the patient received 6st dose of pembrolizumab. The patient received a total of 6 doses of pembrolizumab before presentation. On an unspecified date, 2 days after the 6th dose of pembrolizumab and 7 days after 1st dose of recombinant zoster vaccine, the patient presented with a 2-day history of multiple small oral ulcers. Associated symptoms included fatigue. The oral mucositis was considered nonspecific; thus, an antiseptic solution was prescribed. After 2 days, the patient developed new ulcers in the tongue associated with difficulty swallowing solids. The patient received treatment with acyclovir without improvement. Subsequently, the patient exhibited worsening of ulcers over the lips and a non-pruritic and non-tender rash in the upper back and upper extremities. The physical examination revealed hemorrhagic crust more prominent in the lower lip, showing cracking and fissuring with blood encrustation. Oral mucosa examination showed extensive vesicles with erythematous borders scattered in hard palate, mucosa, and gums. The tongue was denuded, with prominent taste buds and a rough surface appearance. Some scabs were noticed in the upper extremities and upper back without any surrounding erythema. A buccal mucosa biopsy revealed focally ulcerated mildly parakeratotic stratified squamous epithelium overlying fibrovascular connective tissue. The ulcer bed was covered by a fibrin clot composed of enmeshed erythrocytes, neutrophils, and lymphocytes. Numerous ectatic endotheliallined vascular channels were noticed throughout the subjacent connective tissue stroma, which exhibits a diffuse acute and chronic inflammatory cell infiltrate. No immunoreactants (C3, immunoglobulin [Ig] G, IgA, IgM) were detected. The viral culture and polymerase chain reaction did not detect herpes simplex virus. Although the histopathologic findings were nonspecific, when correlated with the clinical presentation and onset of new medications, the findings were compatible with the diagnosis of SJS-like eruption. The patient received prednisone, which slowed the progression of her lesions. The patient had not been maintained on steroid therapy prior. The patient did not receive the second dose of RZV and pembrolizumab was discontinued. At a 1-month follow-up appointment, her initial eruptions improved. Unfortunately, the patient subsequently presented to the hospital with severe sepsis from a perforated duodenal ulcer. On an unspecified date, the patient was died with an unknown cause. It was unknown whether the patient's autopsy was performed or not. This case has been considered serious due to death and hospitalization. The author commented, "SJS is a rare blistering disorder with high mortality rate and significant morbidity. Stevens-Johnson syndrome (SJS) is a life-threating mucocutaneous reaction predominantly induced by drugs. Causes include drugs, herpes viruses, and immunization. The timing of the eruption soon after the receipt of recombinant zoster vaccine suggests a role of vaccination in our patient, yet patients receiving cancer immunotherapy may develop late-onset skin toxicity. Targeted cancer therapies such as pembrolizumab, which has been approved for the treatment of metastatic malignancy, can cause severe skin toxicities, including SJS. They are rare and inconsistently reported. Therefore, we recommend long-term monitoring for mucocutaneous reactions after initiation of pembrolizumab. It is possible that the corticosteroids given for her SJS-like syndrome contributed to her death. The most common drugs associated with SJS are sulfonamide antibiotics, anticonvulsants, nonsteroidal anti-inflammatory drugs, and corticosteroids. Other etiologies, such as viruses (i.e., herpes simplex virus) and vaccinations, have been implicated as a cause of SJS. Some predisposing factors, namely, drug-specific T-cell-mediated cytotoxicity, and genetic susceptibility of the patient (human leukocyte antigen [HLA] and non-HLA genes) may play a role in its pathogenesis. Our patient developed SJS-like eruptions in oral mucosa after 15 weeks of exposure of pembrolizumab (6 doses) and 7 days after 1 dose of RZV. SJS only rarely occurs 8 weeks following suspected drug exposure, but late onset in patients receiving immunotherapy has been reported. Pembrolizumab is usually a well-tolerated therapy for metastatic cancers. The most common immune-related skin lesions reported are lichenoid reaction, eczema, and vitiligo. Pembrolizumab rarely causes skin reactions, but severe responses such as SJS can occur. The latent period between pembrolizumab exposure and onset of symptoms in SJS varies from 7 to 140 days. In addition, gene expression profiles from skin lesions caused by anti-programmed death-1 (anti-PD-1) antibody therapy and SJS has similarities. These findings suggests that anti-PD-1 antibody can induce SJS-like adverse reactions. Furthermore, cases of SJS following herpes zoster vaccination are exceedingly rare. In a recent systematic review, there were 2 post-marketing surveillance studies implicating live-attenuated varicella vaccine with SJS. The immunologic theory behind vaccine-induced cutaneous hypersensitivity states that antigens in the vaccine are expressed on the surface of keratinocytes, generating a CD8+ T lymphocyte immune response against epidermal cells. This leads to apoptosis of keratinocytes and detachment of the dermal-epidermal junction. Our patient received the new vaccine RZV that promotes strong CD4+ T-cell and humoral immune response against recombinant proteins. It is difficult to ignore the appearance of her severe mucocutaneous eruption shortly after she received zoster vaccine, suggesting that herpes virus antigens, perhaps in combination with her immunotherapy, may have induced the cytotoxic skin reaction. However, immunotherapies require time to induce immune responses, and skin immune-mediated adverse effect may take longer to appear compared with cytotoxic therapies." This article corresponding to this case is not available for regulatory submission due to copyright restriction.      Lab Comments: On an unspecified date, lab test were performed. The patient's oral mucosa examination showed extensive vesicles with erythematous borders scattered in hard palate, mucosa, and gums. The tongue was denuded, with prominent taste buds and a rough surface appearance. Some scabs were noticed in the upper extremities and upper back without any surrounding erythema.A buccal mucosa biopsy revealed focally ulcerated mildly parakeratotic stratified squamous epithelium overlying fibrovascular connective tissue. The ulcer bed was covered by a fibrin clot composed of enmeshed erythrocytes, neutrophils, and lymphocytes. Numerous ectatic endotheliallined vascular channels were noticed throughout the subjacent connective tissue stroma, which exhibits a diffuse acute and chronic inflammatory cell infiltrate. The histopathologic findings were nonspecific, when correlated with the clinical presentation and onset of new medications, the findings were compatible with the diagnosis of SJS-like eruption. No immunoreactants. (C3, immunoglobulin [Ig] G, IgA, IgM) were detected.; Reported Cause(s) of Death: unknown cause of death