Remission of refractory esophageal lichen planus induced by tofacitinib.

As of now, there exists no established therapy for ELP. Retinoids, which are standard in treating cutaneous LP, do not exhibit positive effects in ELP. While topical glucocorticosteroids often yield favorable responses in esophageal inflammation, some cases prove recalcitrant or refractory. In such instances, various immunosuppressive therapies have been attempted with variable success.This report details a severe case of ELP that showed resistance to prednisolone, acitretin, alitretinoin, adalimumab, tacrolimus, hydroxychloroquine plus mycophenolate mofetil, and cyclophosphamide. The initiation of the JAK inhibitor tofacitinib induced an impressive clinical, endoscopic, and histological remission. This positive response to a JAK inhibitor is discussed in the context of our evolving understanding of the immune-mediated pathogenesis of this disease.

Comparison between traumatic and atraumatic over-the-scope clips in patients with duodenal ulcer bleeding: a retrospective analysis with propensity score-based matching.

BACKGROUND AND AIMS: Over-the-scope clips (OTSCs) substantially improved the endoscopic armamentarium for the treatment of severe GI bleeding and can potentially overcome limitations of standard clips. Data indicate a superiority of OTSCs in hemostasis as first- and second-line therapy. However, the impact of the OTSC designs, in particular the traumatic (-t) or atraumatic (-a) type, in duodenal ulcer bleeding has not been analyzed so far. METHODS: This was a retrospective analysis of a prospective collected database from 2009 to 2020 of 6 German endoscopic centers. All patients who underwent emergency endoscopy and were treated using an OTSC for duodenal ulcer bleeding were included. OTSC-t and OTSC-a patients were compared by the Fisher exact test, χ2 test, or Mann-Whitney U test as appropriate. A propensity score-based 1:1 matching was performed to obtain equal distribution of baseline characteristics in both groups. RESULTS: The entire cohort comprised 173 patients (93 OTSC-a, 80 OTSC-t). Age, gender, anticoagulant therapy, Rockall score, and treatment regimen had similar distributions in the 2 groups. However, the OTSC-t group showed significantly more active bleeding ulcers (Forrest Ia/b). Matching identified 132 patients (66 in both groups) with comparable baseline characteristics. Initial bleeding hemostasis (OTSC-a, 90.9%; OTSC-t, 87.9%; P = .82) and 72-hour mortality (OTSC-a, 4.5%; OTSC-t, 6.0%; P > .99) were not significantly different, but the OTSC-t group revealed a clearly higher rate of recurrent bleeding (34.9% vs 7.6%, P < .001) and necessity of red blood cell transfusions (5.1 ± 3.4 vs 2.5 ± 2.4 concentrates, P < .001). CONCLUSIONS: For OTSC use, the OTSC-a should be the preferred option for duodenal ulcer bleeding.

[Esophageal Lichen Planus - An Underdiagnosed Disease]. / Der Lichen planus des Ösophagus ­ Eine unterschätzte Erkrankung.

An involvement of the esophagus in patients with lichen planus was described for the first time in 1982. Ever since, it has been seen as a rarity. However, studies over the last 10 years have shown a higher prevalence than expected. It may even be supposed that esophageal lichen planus (ELP) is more common than eosinophilic esophagitis. ELP mostly affects middleaged women. The principal symptom is dysphagia. Endoscopically, ELP is characterized by denudation and tearing of the mucosa, trachealization and hyperkeratosis and esophageal stenosis may occur in patients with long courses of the disease. Histologic findings including mucosal detachment, T-lymphocytic infiltrate, intraepithelial apoptosis (civatte bodies) and dyskeratosis are crucial. Direct immunofluorescence shows fibrinogen deposits along the basement membrane zone. So far, there is no well-established therapy but a treatment with topic steroids is effective in 2/3 of the patients. Common therapy of lichen planus of the skin seems to be ineffective for treatment of ELP. Symptomatic esophageal stenosis should be endoscopically dilated. ELP joins the group of "new" immunologic diseases of the esophagus.

[Esophageal Lichen Planus - an Underdiagnosed Disease]. / Der Lichen planus des Ösophagus ­ Eine unterschätzte Erkrankung.

An involvement of the esophagus in patients with lichen planus was described for the first time in 1982. Ever since, it has been seen as a rarity. However, studies over the last 10 years have shown a higher prevalence than expected. It may even be supposed that esophageal lichen planus (ELP) is more common than eosinophilic esophagitis. ELP mostly affects middle-aged women. The principal symptom is dysphagia. Endoscopically, ELP is characterized by denudation and tearing of the mucosa, trachealization and hyperkeratosis and esophageal stenosis may occur in patients with long courses of the disease. Histologic findings including mucosal detachment, T-lymphocytic infiltrate, intraepithelial apoptosis (civatte bodies) and dyskeratosis are crucial. Direct immunofluorescence shows fibrinogen deposits along the basement membrane zone. So far, there is no well-established therapy but a treatment with topic steroids is effective in 2/3 of the patients. Common therapy of lichen planus of the skin seems to be ineffective for treatment of ELP. Symptomatic esophageal stenosis should be endoscopically dilated. ELP joins the group of "new" immunologic diseases of the esophagus.

[Viral hepatitis A-E]. / Virushepatitis A­E.

Hepatitis viruses A-E cause acute and chronic liver inflammation and thus lead to significant morbidity and mortality worldwide. They differ significantly in their biology, course of disease and therapy options. While hepatitis A virus only causes acute infection, hepatitis B can become chronic, even reactivate or occur as coinfection with hepatitis D virus. Whereas these infections are preventable through vaccination, a vaccine does not exist against HCV. However, new direct antiviral agents reliably lead to cure of chronic hepatitis C. Hepatitis E virus frequently causes acute or-in case of immunosuppression-even chronic hepatitis. Continual screening of patients with elevated liver enzymes or risk groups using simple serological markers can enable virus-specific therapy of mostly asymptomatic chronic virus hepatitis, preventing the development of liver cirrhosis and hepatocellular carcinoma.

Prolonged SARS-CoV-2 shedding and mild course of COVID-19 in a patient after recent heart transplantation.

In the coronavirus disease 2019 (COVID-19) pandemic, organ transplant recipients are considered to be at high risk for an unfavorable outcome. However, in particular the role of immunosuppression in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains undetermined. Here, we present a 62-year-old male COVID-19 patient with recent heart transplantation who developed only mild symptoms, but had prolonged virus shedding, and summarize the available data on COVID-19 in cardiac allograft recipients. Initially the patient presented with a transient episode of fever and sore throat but no other symptoms, in particular no cough or dyspnea at rest. After diagnosis, immunosuppression was continued unchanged. On day 7, his temperature increased again with concurrent mild rise of C-reactive protein, IL-6, and pro-B-type natriuretic peptide levels. Hydroxychloroquine was started and continued for 7 days. While the patient no longer had clinical symptoms 20 days after initial presentation, virus culture of throat swabs on days 18 and 21 confirmed active virus replication and SARS-CoV-2 PCR remained positive on day 35 with copy numbers similar to the onset of infection. In conclusion, the immunosuppression regimen in transplant recipients with mild COVID-19-associated symptoms may be continued unchanged. However, it may contribute to delayed virus polymerase chain reaction conversion and thus possible prolonged infectivity.

Esophageal lichen planus: Current knowledge, challenges and future perspectives.

Lichen planus (LP) is a frequent, chronic inflammatory disease involving the skin, mucous membranes and/or skin appendages. Esophageal involvement in lichen planus (ELP) is a clinically important albeit underdiagnosed inflammatory condition. This narrative review aims to give an overview of the current knowledge on ELP, its prevalence, pathogenesis, clinical manifestation, diagnostic criteria, and therapeutic options in order to provide support in clinical management. Studies on ELP were collected using PubMed/Medline. Relevant clinical and therapeutical characteristics from published patient cohorts including our own cohort were extracted and summarized. ELP mainly affects middle-aged women. The principal symptom is dysphagia. However, asymptomatic cases despite progressed macroscopic esophageal lesions may occur. The pathogenesis is unknown, however an immune-mediated mechanism is probable. Endoscopically, ELP is characterized by mucosal denudation and tearing, trachealization, and hyperkeratosis. Scarring esophageal stenosis may occur in chronic courses. Histologic findings include mucosal detachment, T-lymphocytic infiltrations, epithelial apoptosis (Civatte bodies), dyskeratosis, and hyperkeratosis. Direct immuno-fluorescence shows fibrinogen deposits along the basement membrane zone. To date, there is no established therapy. However, treatment with topical steroids induces symptomatic and histologic improvement in two thirds of ELP patients in general. More severe cases may require therapy with immunosuppressors. In symptomatic esophageal stenosis, endoscopic dilation may be necessary. ELP may be regarded as a precancerous condition as transition to squamous cell carcinoma has been documented in literature. ELP is an underdiagnosed yet clinically important differential diagnosis for patients with unclear dysphagia or esophagitis. Timely diagnosis and therapy might prevent potential sequelae such as esophageal stenosis or development of invasive squamous cell carcinoma. Further studies are needed to gain more knowledge about the pathogenesis and treatment options.

Characterization of pre-existing and induced SARS-CoV-2-specific CD8+ T cells.

Emerging data indicate that SARS-CoV-2-specific CD8+ T cells targeting different viral proteins are detectable in up to 70% of convalescent individuals1-5. However, very little information is currently available about the abundance, phenotype, functional capacity and fate of pre-existing and induced SARS-CoV-2-specific CD8+ T cell responses during the natural course of SARS-CoV-2 infection. Here, we define a set of optimal and dominant SARS-CoV-2-specific CD8+ T cell epitopes. We also perform a high-resolution ex vivo analysis of pre-existing and induced SARS-CoV-2-specific CD8+ T cells, applying peptide-loaded major histocompatibility complex class I (pMHCI) tetramer technology. We observe rapid induction, prolonged contraction and emergence of heterogeneous and functionally competent cross-reactive and induced memory CD8+ T cell responses in cross-sectionally analyzed individuals with mild disease following SARS-CoV-2 infection and three individuals longitudinally assessed for their T cells pre- and post-SARS-CoV-2 infection. SARS-CoV-2-specific memory CD8+ T cells exhibited functional characteristics comparable to influenza-specific CD8+ T cells and were detectable in SARS-CoV-2 convalescent individuals who were seronegative for anti-SARS-CoV-2 antibodies targeting spike (S) and nucleoprotein (N). These results define cross-reactive and induced SARS-CoV-2-specific CD8+ T cell responses as potentially important determinants of immune protection in mild SARS-CoV-2 infection.