Allergic contact dermatitis (ACD) most commonly presents as an eczematous reaction; however, a variety of non-eczematous eruptions have also been reported, including erythema multiforme (EM)-like lesions. 1-3 The pathogenesis of true EM is known to be type III hypersensitivity immune complex-mediated, affecting small vessels in the skin and mucosa. 4 The pathogenesis of EM-like lesions which appear secondary to ACD, however, remains elusive but is hypothesized to be a result of a type IV reaction mediated by T cells, as is the case in eczematous contact dermatitis. 2,5 We herein present a case of ACD in a pediatric patient who subsequently developed an EM-like reaction and discuss this potentially underreported complication to plant-induced contact dermatitis.
The immune contexture of pancreatic ductal adenocarcinoma (PDAC) is generally immunosuppressive. A role for immune checkpoint inhibitors (ICIs) in PDAC has only been demonstrated for the rare and hypermutated mismatch repair (MMR) deficient (MMR-d) subtype. Homologous recombination repair (HR) deficient (HR-d) PDAC is more prevalent and may encompass up to 20% of PDAC. Its genomic instability may promote a T-cell mediated anti-tumor response with therapeutic sensitivity to ICIs. To investigate the immunogenicity of HR-d PDAC, we used multiplex immunohistochemistry (IHC) to compare the density and spatial distribution of CD8+ cytotoxic T-cells, FOXP3+ regulatory T-cells (Tregs), and CD68+ tumor-associated macrophages (TAMs) in HR-d versus HR/MMR-intact PDAC. We also evaluated the IHC positivity of programmed death-ligand 1 (PD-L1) across the subgroups. 192 tumors were evaluated and classified as HR/MMR-intact (n=166), HR-d (n=25) or MMR-d (n=1) based on germline testing and tumor molecular hallmarks. Intra-tumoral CD8+ T-cell infiltration was higher in HR-d versus HR/MMR-intact PDAC (p<0.0001), while CD8+ T-cell densities in the peri-tumoral and stromal regions were similar in both groups. HR-d PDAC also displayed increased intra-tumoral FOXP3+ Tregs (p=0.049) and had a higher CD8+:FOXP3+ ratio (p=0.023). CD68+ TAM expression was similar in HR-d and HR/MMR-intact PDAC. Finally, 6 of the 25 HR-d cases showed a PD-L1 Combined Positive Score of >=1, whereas none of the HR/MMR-intact cases met this threshold (p<0.00001). These results provide immunohistochemical evidence for intra-tumoral CD8+ T-cell enrichment and PD-L1 positivity in HR-d PDAC, suggesting that HR-d PDAC may be amenable to ICI treatment strategies.
Question: A 17-year-old boy with high risk acute lymphoblastic leukemia, post bone marrow transplant (BMT), presented with 6 months of progressively worsening diarrhea and weight loss. He was treated for skin graft-versus-host disease (GVHD) 2 months earlier, and had also been treated twice for clostridium difficile infections. He was admitted to hospital with lower abdominal pain that was severe enough to require narcotics. In hospital, he was passing up to 10 loose nonbloody stools per day and vomiting 3-4 times a day (nonbilious). These symptoms were limiting his oral intake and he was put on continuous nasogastric tube feeds. There was no history of fever, travel or sick contacts.On examination he was hemodynamically stable. His abdomen was diffusely tender to palpation, with normal bowel sounds, no peritoneal signs and no organomegaly. The perianal examination was normal. He also had a generalized erythematous sand-paper-like rash.Laboratory tests showed a normocytic normochromic anemia (hemoglobin 88 g/L), mild leukopenia, and mild thrombocytopenia. Albumin was 25 g/L. His electrolytes, creatinine, and liver panel were normal. Inflammatory markers had not been done on admission. His stool test came back positive again for Clostridium difficile.He was treated for C difficile, initially receiving oral vancomycin, after which IV metronidazole was added. Despite appropriate management for the c. difficile, there was no improvement in the diarrhea or pain. Upper endoscopy and flexible sigmoidoscopy were therefore done for further assessment.What is the diagnosis? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI.
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