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Background: In recent years, the emergence of immunotherapy has renewed therapeutic modality. Different from traditional anti-tumor therapy, immune-related adverse events of skin, gastrointestinal tract, liver, lung, endocrine glands commonly occurred. At present, only one case of immune-related adverse event of Behcet's-like syndrome following pembrolizumab treatment was reported in USA, and no one is reported in China., Case Presentation: Here, we report a rare case of Behcet's-like symptom following pembrolizumab treatment. A 43-year-old female was diagnosed as lymph node and bone metastasis of adenocarcinoma with unknown primary lesion, probably being of pulmonary origin. She was treated with pembrolizumab 200 mg every three weeks in combination with chemotherapy for 6 cycles, followed by pembrolizumab monotherapy maintenance. However, she developed Behcet's-like syndrome with oral ulcer, genital uler, phlebitis, and vision loss after 9 cycles of pembrolizumab treatment. She was treated with prednisone 5 mg orally three times a day. Two weeks later, dose of glucocorticoid gaven to the patient gradually decreased with improved symptoms. After a treatment-free withdrawal period, the patient requested to continue pembrolizumab treatment. Unfortunately, the above symptoms recurred on the second day following pembrolizumab treatment, and glucocorticoid was taken once again. The symptoms improved and the condition was under control., Conclusions: In view of the exponential growth of immunocheckpoint inhibitors (ICIs) in a variety of tumors, we should be alert to related adverse events, especially the rare rheumatic manifestations., (© 2024. The Author(s).)

Vascular involvement in Behçet's disease (BD) occurs in up to 50% of patients. The main mechanism of thrombosis is inflammation. Thus, immunosuppressants (IS) are the mainstay of therapy, and adding anticoagulation (AC) is controversial. In daily practice, we observed that patients who received AC in combination with IS experienced less recurrent thrombosis and decided to investigate our BD patients retrospectively. We hypothesized that adding AC to immunosuppressive therapy may lower the risk of recurrent thrombosis. Treatment at the time of first or recurrent thrombotic events was recorded. Events under the only IS and IS + AC treatments were compared. There were 40 patients (33 males). The most common types of first vascular events were deep vein thrombosis (77.5%) followed by pulmonary embolism (PE) (52.5%). One patient did not receive any treatment. Among the 39 patients, 32 received glucocorticoid and at least one of the azathioprine, or cyclophosphamide, anti-TNF, 5 received monotherapy with azathioprine, 1 received monotherapy with corticosteroid, and the remaining 1 received monotherapy with cyclophosphamide. In total, 22 patients (55%) experienced 27 recurrent venous thromboembolism (VTE) events. Two (7.4%) events while only on AC, 2 (7.4%) events while on AC + IS, and 15 (55.5%) events occurred while on only IS. Eight (19.6%) patients were not receiving any treatment during relapses. The recurrence rate was statistically significantly lower in the IS + AC treatment group compared to IS alone. In conclusion, IS are the mainstay of treatment for BD, and adding AC may help to lower the recurrence risk of thrombotic events., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: This study aimed to review effectiveness studies comparing two biological anti-tumour necrosis factor agents, adalimumab (ADA) and infliximab (IFX), in the management of autoimmune uveitis., Methods: A systematic search was conducted across PubMed, Scopus, Web of Science and Google Scholar from 2014 until February 2022. The search included the following keywords "Adalimumab", "Infliximab", "Autoimmune", "Anterior", "Intermediate", "Posterior", "Panuveitis", "Refractory" and "Uveitis". Primary studies comparing both ADA and IFX in a population of autoimmune uveitis patients were considered. Outcomes of interest were measures of response to treatment and incidence of adverse events., Results: The preliminary literature search generated 7156 references. Six studies fulfilled the eligibility criteria and were included in the final analysis; all were non-randomised, retrospective or observational. The included studies found similar effectiveness and side effect profiles for both ADA and IFX in the management of autoimmune uveitis, however, one did not report effectiveness for each separately, and three were limited to Behcet's disease., Conclusion: ADA and IFX seem to display comparable effectiveness and safety profiles. However, the available evidence remains scarce, of low quality and at high risk of bias. A direct comparison between ADA and IFX through large randomised controlled trials is needed to provide more substantial evidence of equivalence or superiority in uveitis., Competing Interests: Competing interests: NAVB declares a speaker fee from Alimera Sciences in autoimmune uveitis within the last 3 years., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Objective: The use of biological agents in the treatment of ocular Behçet's disease has recently become more frequent. The use of two agents, infliximab (IFX) and adalimumab (ADA), for the treatment of Behçet's disease requires prior approval by the Turkish Medicines and Medical Devices Agency. We report on a review of such applications with a view to informing on how such agents are used off-label in Turkey., Methods: Prescriptions for off-label use of IFX or ADA sent from hospitals in Turkey to the Turkish Medicines and Medical Devices Agency in 2018 were evaluated. Demographic data, previous treatment regimens and reasons for referral were extracted from the files of the cases., Results: A total of 662 patients were considered for off-label use of IFX or ADA for the treatment of ocular Behçet's disease. The mean age of the patients was 35.7±10.8 years (range 12-76); 61.5% of patients were men and 38.5% were women. Of the applications, 345 (52.1%) were for IFX and 317 (47.9%) for ADA. Among the referring hospitals, the public university hospitals ranked first, accounting for 77.9% of IFX and 88.6% of ADA prescriptions. Most applications were made after the failure of conventional therapy, which included steroids and immunosuppressive agents., Conclusion: IFX and ADA are rarely used as initial therapy. Stepwise treatment is still preferred in the treatment of ocular Behçet's disease in Turkey. Our report informs on the management of this difficult-to-treat condition., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The landscape for the treatment of metastatic melanoma has been revolutionized with the introduction immune checkpoint inhibitors. Immune checkpoint inhibitors have now become the standard of care for the treatment of cancers. These immune agents including programmed death receptor-1 inhibitors, programmed death-ligand 1 inhibitors and cytotoxic T-lymphocyte antigen-4 inhibitors have shown promising results but have been associated with numerous immune-related complications. Pembrolizumab, a programmed death receptor-1 inhibitor, has been associated with a number of immune-related adverse events affecting multiple organ systems including integument, ocular, endocrine, cardiovascular, pulmonary, renal, gastrointestinal, and musculoskeletal system., Case Report: We present a case of an 88-year-old Caucasian male with metastatic melanoma of the face with metastasis to the right fifth cranial nerve and into the right cavernous sinus. He underwent resection of the melanoma and was placed on pembrolizumab at 2 mg/kg every three weeks. Interestingly, 24 months on pembrolizumab therapy, he developed corneal erosions, oral and genital ulcerations., Management and Outcome: Patient completed his 24 months of pembrolizumab and was started on prednisone and colchicine with improvement in his symptoms. At his follow-up eight months, he had recurrence of an oral ulcer., Discussion: Here we present a rare case of an elderly male on pembrolizumab who suffered from corneal erosions, oral and genital ulcers, a syndrome similar to Behcet's disease. Given that pembrolizumab and other immune checkpoint inhibitors are being utilized in the treatment of cancers, physicians should be aware of the wide range immune-related adverse events including the possible Behcet's-like syndrome presentation.

Purpose: To describe an unusual case of frosted branch angiitis that developed in a patient with acute onset systemic vasculitis possibly triggered by the antithyroid medication methimazole., Methods: We conducted a thorough review of the medical records of a 16-year-old female patient who presented with frosted branch angiitis. During the initial hospital admission, the patient underwent an extensive systemic workup to determine the etiology of her disease and ophthalmologic testing including fundus photographs and fluorescein angiography., Results: Our patient presented with a unilateral acute onset loss of vision, whose fundus examination revealed the pathognomonic features of frosted branch angiitis. Extensive systemic workup revealed an antineutrophilic cytoplasmic antibody-positive vasculitis, possibly triggered by methimazole., Conclusion: This case is the first reported frosted branch angiitis associated with a drug-induced antineutrophilic cytoplasmic antibody-positive vasculitis triggered by methimazole.

Central neurological involvement in Behcet's disease (neuro-Behcet) occurs in 10 to 20% out of the patient. We report a 47-year-old man treated with cyclosporine who presented with neurologic manifestations of Behçet's disease. Relationship between cyclosporine and neuro-Behcet's disease are discussed., (Copyright © 2010 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Objective: Immunization of rats with alpha-tropomyosin (TPM) led to arthritis, uveitis and dermatitis, typical features of Behçet's disease (BD). The present study characterizes the arthritic features of this animal model, not previously described., Methods: Lewis rats were immunized with bovine alpha-TPM and another group of rats was treated with neutralizing anti- tumor necrosis factor-alpha (TNF-alpha) antibodies., Results: Clinically more than 90% of the immunized rats developed severe acute arthritis 12 days after vaccination. Rats that were followed-up for 6 months had persistent inflammation of the leg joints. Histologic studies demonstrated predominant mononuclear infiltrations in the acute phase of arthritis; the chronic arthritic process resulted in cartilage and bone damage and abundant fibrosis which led to joint deformations. Male and female rats had a similar clinical course. Analysis of the splenocyte cytokine profile kinetics revealed a persistently high level of interferon-gamma (INF-gamma) and an increase in TNF-alpha secretion during the acute phase. Increasing levels of interleukin (IL)-10 heralded the decline in clinical arthritis. No IL-4 was detected. No arthritis was detected in the rats treated with anti-TNF-alpha antibodies., Conclusion: The data indicates that alpha-TPM serves as an autoantigen to induce acute and chronic destructive arthritis in rats. This model is a TNF-alpha dependent autoimmune disease, with a Th1 cytokine profile.

A 77-year-old man was diagnosed as having essential thrombocythemia in 1992. Treatment with hydroxyurea was started in 1997, which stabilized the platelet count. The patient then suffered from pharyngalgia and rhinitis with a high fever, immediately after which he developed tarry stools and anemia and was admitted to our hospital. The physical examination revealed splenomegaly, oral aphthous ulcers, genital ulcers and skin lesions on the lower limbs. His hematological and biochemical tests revealed anemia and increased level of C-reactive protein. He also had an HLA-B51 phenotype. The findings of gastro-intestinal and colon fiberoscopy showed a duodenal ulcer and multiple ulcers on ascending colon. He was thus diagnosed as having intestinal tract-type Behçet disease. After withdrawal of the hydroxyurea administration, the intestinal ulcers, oral aphthous ulcers and genital ulcers improved.

Involvement of the brain is one of the most important complications of Behçet's disease, but its diagnosis is difficult because of the lack of effective imaging tools. Therefore, technetium-99m ethyl cysteinate dimer (Tc-99m ECD) single-photon emission computed tomography (SPECT) of the brain was used to detect abnormal regional cerebral blood flow in patients with neuro-Behçet's syndrome (NBS). Tc-99m ECD brain SPECT was performed to detect hypoperfusion areas of the brain in 10 NBS patients with definite neuropsychiatric symptoms or signs and normal brain magnetic resonance imaging (MRI) findings. Tc-99m ECD brain SPECT demonstrated hypoperfusion areas of the brain in all of the 10 NBS patients. The parietal lobes were the most common areas with hypoperfusion lesions. Tc-99m ECD brain SPECT is a more sensitive and useful tool than brain MRI for detecting hypoperfusion areas of the brain in NBS patients.

Behcet's disease (BD) is a chronic, relapsing vasculitis of unknown etiology. Its association with chronic myelogenous leukemia (CML) is extremely rare, and typical manifestations of BD were observed in a very few patients with CML, mainly under interferon-alpha (IFN-alpha) treatment. Skin pathergy test, being positive in about 50% of patients with BD, is also positive in some IFN-alpha-treated patients with CML without any evidence of BD symptoms. We describe a 62-year-old woman with CML who developed characteristic features of BD, including a positive skin hyperactivity test, during treatment with hydroxyurea. Hydroxyurea has been implicated in the appearance of skin vasculitic ulceration, but this is the first case, according to our knowledge, where the development of BD was observed during hydroxyurea maintenance in the chronic phase of CML.

Systemic administration of steroids to patients with Behçet's disease in Japan is often followed by a worsening in ocular symptoms. The sensitivity of 7 patients with Behçet's disease to steroids which were administered during and after intraocular surgery was therefore measured, and their postoperative course was reviewed. Three of the 7 showed a low steroid sensitivity, and the frequency of postoperative inflammatory episodes and the intraocular pressure were both higher for this group than for the 4 who showed high steroid sensitivity., (Copyright 2000 S. Karger AG, Basel.)

Two patients with chronic myelogenous leukemia (CML) who developed characteristic features of Behçet's disease (BD) during alpha-interferon (IFN-alpha) treatment and another patient who had a diagnosis of BD preceding CML are presented. In the first two patients, features of BD appeared 6 months after the initiation of IFN-alpha treatment: they included recurrent oral aphthae, genital ulceration, arthritis, folliculitis, and a positive skin pathergy test. The third patient, however, had a diagnosis of Behçet's disease 4 years before diagnosis of Philadelphia-positive CML. We prospectively examined the skin pathergy reaction in a group of patients with CML, multiple myeloma, and hairy cell leukemia both before and after IFN-alpha treatment and found two additional patients with CML who developed a positive skin pathergy test following IFN-alpha treatment.

Behçet's disease is a chronic inflammatory disorder characterized by the triad of oral and genital ulcers and ocular lesions. One of the most life-threatening manifestations results from involvement of the central nervous system, presenting as necrotising meningo-encephalitis, most typically affecting the brain stem, internal capsula and basal brain ganglia. We report on a young Caucasian mate with Behçet's disease (HLA B 51+) and recurrent uveitis, who presented with acute neurologic involvement under CyA therapy 5 years after first diagnosis. At the time of admission MRI showed two high intensity lesions in the brain stem on T1 weighted images enhanced with Gd-DTPA, reflecting active inflammation. Shortly after admission the CyA treatment was stopped and a therapy with high dose steroids and chlorambucil, starting with a dose of 2 mg daily was initiated. This led to improvement of neurologic symptoms, also documented by brain stem evoked potentials and investigations of cerebrospinal fluid, as well as of ophtalmologic symptoms within few days of treatment. Steroids were reduced to a maintenance dose of 12 mg Prednyliden daily. The brain MRI taken 8 weeks after onset of chlorambucil treatment showed the same lesions in the brain stem, with low intensity in the T1 weighted images an no longer enhanced Gd-DTPA uptake. Chlorambucil dose was reduced to 2 mg every second day after 8 months. There was no exacerbation in the follow-up of 12 months. We conclude that a 6-week Chlorambucil therapy consisting of 2 mg/p.o./d led to remission of neurologic involvement firstly evolving under CyA-medication which suggests superiority of chlorambucil as a treatment modality in neurologic as well as ophtalmologic features of the disease.

A 34-year-old man with neuro-Behçet disease showed bilateral cheiro-oral syndrome following simultaneous multiple brain hemorrhage. The patient suddenly developed fever, headache, right-sided heminumbness, and gait disturbance after ciclosporin therapy was instituted. Bilateral uveitis, oral aphthous ulcers and follicular skin eruptions were observed. Neurologically, apathetic state, horizontal gaze palsy, spastic paraparesis with right Babinski sign, gait difficulty, and painful dysesthesia of perioral regions, right upper and lower extremities and left hand were revealed as main symptoms. Erythrocyte sedimentation rate was elevated and C-reactive protein was positive. Cerebrospinal fluid examination showed lymphocytic pleocytosis. A brain CT scan demonstrated focal high density areas with slight contrast enhancement in the median region of the tegmentum of pons, and in the subcortex of right superior parietal lobe. T1, T2 and proton density images of MRI taken 50 days after the onset disclosed small irregular low signal intensities in the lesions that correspond to the CT findings. Corticosteroid was administered immediately after admission, which resulted in a rapid improvement of clinical symptoms and a complete disappearance of laboratory abnormalities and CT changes. As dysesthesia was attenuated, bilateral typical symptoms of cheiro-oral syndrome were found. These results suggest that the intracerebral hemorrhage was caused by angitis related to Behçet disease. MRI findings implicate that the involvement of bilateral paramedian areas including medial parts of both the medial leminiscus and the ventral secondary ascending tract of the trigeminal nerve is responsible for bilateral cheiro-oral syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)