UNASSIGNED: The majority of patients with autoimmune hepatitis (AIH) achieve complete remission with established treatment regiments. In patients with intolerance or insufficient response to these drugs, the remaining options are limited and novel treatment approaches necessary. In primary biliary cholangitis (PBC), ursodeoxycholic acid (UDCA) and fibrates have improved prognosis dramatically, but there remains a proportion of patients with refractory disease.In patients with refractory AIH and/or PBC, we used a novel treatment strategy with the anti-B cell activating factor, belimumab. The first three patients had concomitant Sjögren\'s disease. The connecting element between all three diseases is B cell activation, including elevated levels of the B cell activating factor (BAFF). Furthermore, belimumab has been shown to be beneficial in Sjögren\'s disease.
UNASSIGNED: To retrospectively investigate treatment response in six patients with AIH or PBC with or without concomitant Sjögren\'s disease treated with the anti-BAFF therapy belimumab at the University Hospital in Bern, Switzerland.
UNASSIGNED: In all three patients with AIH, belimumab improved disease control and helped by-pass or reduce problematic side effects from corticosteroids and calcineurin inhibitors. In PBC patients (n = 3), there was no clear improvement of liver function tests, despite reduction or normalization of IgM. All patients with concomitant Sjögren\'s disease (n = 3) had an improvement of sicca symptoms and two out of three patients experienced an initially marked reduction in fatigue, which lessened over time.
UNASSIGNED: Belimumab may be a promising treatment option for patients with AIH and further investigations are needed. In PBC however, response was not convincing. The effects on sicca symptoms and fatigue were encouraging.

UNASSIGNED: The objectives were to characterize the liver kidney microsome (LKM) antibody profile of a 14-month-old girl with autoimmune hepatitis and analyze the laboratory prevalence of LKM positivity.
UNASSIGNED: This is retrospective analysis of the LKM antibody immunofluorescence tests performed by the Immunology Laboratory of Johns Hopkins Hospital from September 8, 2020 to July 31, 2022. LKM positive sera were also tested by an ELISA for LKM1 antibodies, which recognize the cytochrome P450 2D6 antigen. In silico analysis of 2D6 mRNA expression across anatomical sites was performed using Bgee and GTEx Portal databases.
UNASSIGNED: Of the total of 1598 patients (893 F, 705 M, ages 0.8-94 years) tested for LKM antibodies, 3 were positive, yielding a 0.2% period prevalence. The clinical diagnosis was autoimmune hepatitis in the index case, acute viral hepatitis in a 3-yo male, and hepatocellular carcinoma in a 54-yo male. LKM antibodies yielded the classical homogenous staining pattern in the liver cytosol and proximal kidney tubular cells. The first two patients were also positive for LKM1 antibodies, whereas the third was negative. 2D6 mRNA was expressed highly in the liver, moderately in the duodenum, and minimally in other tissues.
UNASSIGNED: Overall, LKM antibodies are rare. They contribute to establish a diagnosis of autoimmune hepatitis, although they are also found in other liver diseases. The cytochrome P450 2D6 is one of the antigens recognized by LKM antibodies, but other antigens are likely targeted considering that 2D6 is minimally expressed in the kidney and yet LKM antibodies bind to kidney tubuli.

UNASSIGNED: The objective of the study is to report a case of ocular manifestations in a patient with hydralazine-induced vasculitis.
UNASSIGNED: An 88-year-old female was admitted for lower gastrointestinal bleeding. Nine days after admission, she developed bilateral conjunctival chemosis and injection, which rapidly progressed into grouped blistering eruptions of the periorbital skin, face, and neck. After extensive testing and evaluation, her constellation of findings was diagnosed as hydralazine-induced vasculitis. Treatment with intravenous steroids and discontinuation of hydralazine resulted in improvement of the cutaneous and ocular manifestations. Herein we describe the clinical course of an adult patient with symptoms and signs consistent with hydralazine-induced vasculitis to highlight that ophthalmological manifestations can be the first symptoms in patients with life-threatening dermatological conditions.
UNASSIGNED: To our knowledge, this report is the first case of hydralazine-induced vasculitis initially presenting with ocular manifestations.

Immune checkpoint inhibitors (ICIs) improve clinical outcomes in patients suffering from different types of cancer. Liver toxicity is one of the immune-related adverse events associated with immunotherapy; although not common, its management is challenging as it is extremely heterogeneous in terms of presentation and severity. Differences in the development and evolution of ICI-related toxicity in healthy or cirrhotic livers have not yet been elucidated. Assessing causality is key to diagnosing ICI-induced liver toxicity; liver biopsies can assist not only in the differential diagnosis but also in assessing the severity of histological liver damage. The current classification of severity overestimates the grade of liver injury and needs to be revised to reflect the views of hepatologists. Spontaneous improvements in ICI-related liver toxicity have been reported, so corticosteroid therapy should probably be individualised not systematic. The reintroduction of ICIs in a patient with previous immune-mediated hepatitis may be possible, but the risk/benefit ratio should be considered, as the risk factors for hepatitis recurrence are currently unclear. The management of these patients, requiring a balance between efficacy, toxicity and specific treatments, necessitates multidisciplinary collaboration. The incidence of immune-related liver toxicity will continue to rise based on the increasing use of ICIs for most cancers, mandating improved understanding and management of this complication.

UNASSIGNED: Chronic Spontaneous Urticaria (CSU) is a relatively common immune mediated disease that can be effectively treated nowadays. Nevertheless, for some patients remission cannot be achieved following current treatment recommendations, defined as resistant CSU (r-CSU). Treating r-CSU is challenging, and, currently, there are no recommended interventions. In this real-life study we describe successful therapy of 18 r-CSU patients using an \"intensified protocol\" of anti-IgE-antibody (omalizumab) concomitantly with an immunosuppressant. We defined the r-CSU phenotype and compared it to omalizumab-responsive CSU (Or-CSU) phenotype.
UNASSIGNED: Clinical and serological data of 72 CSU patients (ie, 18 r-CSU and 54 age and sex matched Or-CSU) were retrospectively collected and analyzed. All patients were diagnosed with CSU for ≥6 months and treated at the Sheba Medical Center during 2013-2018.
UNASSIGNED: Of 289 CSU patients, 18 (6%) were diagnosed with r-CSU and treated with the \"intensified protocol\" including omalizumab and cyclosporine-A (16p), methotrexate (1p), and azathioprine (1p). Of which, 14/18 (78%) achieved complete remission, 2/18 (11%) partial remission, and 2/18 (11%) no remission. During follow-up no serious adverse events were documented. r-CSU patients received higher doses of antihistamine (p < 0.0001) and omalizumab (425 ± 58 mg/month vs. 283 ± 86 mg/month; p < 0.0001) compared to Or-CSU. The r-CSU phenotype was linked with concomitant autoimmunity (p = 0.0005) and a lower level of IgE prior to initiation of therapy (p = 0.027).
UNASSIGNED: r-CSU may be a distinct CSU phenotype characterized by severe disease, concomitant autoimmunity, and lower baseline-IgE levels (low \"autoallergy\"). An \"intensified protocol\" with omalizumab and an immunosuppressive agent was found to be efficacious and safe for r-CSU. Further larger studies are required to verify these results.

Genetic factors and gene polymorphisms leading to the onset of autoimmune response in autoimmune hepatitis (AIH) are still not full elucidated. Since the CTLA-4 molecule is a key modulator of the lymphocytes responses we hypothezied that deficiencies or mutations in the gene encoding CTLA4 protein may be involved in AIH susceptibility and trigger the autoimmune response. We investigated 3 distinct polymorphic sites (+49A > G, CT60 G > A and -318C > T) of the CTLA4 gene in 50 AIH patients and 100 healthy controls using the KASP genotyping technology. A significant positive association with AIH susceptibility was found for the GG genotype in +49 position of the CTLA4 gene which was significantly higher in AIH patients compared to controls (28% vs 9%, p = 0.003, OR = 3.93 [1.56-9.88]). The CTLA4 A/A genotype in position CT60 was more significantly frequent in controls comparing to AIH patients and could be considered as a protective genotype for the tunisian patients. CTLA4 genotyping in position -318 did not show any statistically significant difference in genotype or allele distribution. The CTLA4 gene polymorphism in position +49 is associated to AIH susceptibility in the Tunisian population. Mutation in the CTLA4 gene may lead to a modification of the CTLA4 protein structure that could have functional relevance in AIH pathogenesis and onset.

A 63 year old female was admitted for investigation of worsening renal insufficiency. During hospitalization she developed persistent immune thrombocytopenia refractory to supportive or immunosuppressive treatment. She was diagnosed with Mycobacterium chimaera prosthetic valve endocarditis and thrombocytopenia resolved with anti-mycobacterial therapy.

Leishmaniasis or kala-azar is a protozoan disease that can present as cutaneous, mucocutaneous, visceral, and disseminated disease. In India, it is usually localized in distinct areas of Bihar, Jharkhand, West Bengal, and parts of Eastern Uttar Pradesh. Visceral leishmaniasis (VL) involves the visceral organs, mainly the liver, the spleen and bone marrow. VL is characterized by prolonged fever, massive splenomegaly, weight loss, progressive anemia, pancytopenia, and hypergammaglobulinemia, and can be complicated by serious infections. In most of the patient the diagnosis is made on bone marrow biopsy or splenic aspirate. We hereby present an unusual case of kala-azar in a 52-year-old patient non-resident of endemic area presenting with pyrexia of unknown origin, in whom bone marrow biopsy was negative for Leishmanin Donovan (LD) bodies, and diagnosis was made by liver biopsy in which LD bodies were seen.

Visceral leishmaniasis is an infection with an insidious and disabling course caused by parasites of the genus Leishmania. In Europe, it is mostly associated with HIV infection. Systemic lupus erythematosus and its treatment are associated with increased risk of infection, neoplastic and concomitant autoimmune disorders. The association of these diseases may go unnoticed. A 60 year-old Caucasian woman with lupus presented with a one-year history of fever, malaise, weakness and weight loss. The highlights on physical examination were pallor, palpable hepatosplenomegaly and low-grade fever. Blood tests showed pancytopenia, hyperproteinemia with hypoalbuminemia and hypergammaglobulinemia; electrophoresis showed a polyclonal gamma curve. Full-body CT scan revealed massive hepatosplenomegaly. Microbiology investigation was negative for the most common pathogens, including tuberculosis. There were no signs of hematologic malignancy in the bone marrow smear. PCR for Leishmania infantum was positive both in blood and bone marrow. The patient was treated with liposomal amphotericin B, and immunosuppression was adjusted. She showed rapid clinical improvement and 6 months later had no signs of disease. The differential diagnosis in a patient with lupus presenting with fever and multisystemic manifestations includes infectious or neoplastic disorders. The patient lived in an endemic area of Leishmania, and typical clinical and analytical changes were all present, making this case highly educational. The case highlights the importance of a patient\'s epidemiological background and how it can lead to the diagnosis and timely treatment of a rare disease.