Project description:Bullous pemphigoid (BP) is a rare, life-threatening autoimmune blistering disease with pruritus and tension blisters/bullous as the main clinical manifestations. Glucocorticosteroids are the main therapeutic agents for it, but their efficacy is poor in some patients. Tofacitinib, a small molecule agent that inhibits JAK1/3, has shown incredible efficacy in a wide range of autoimmune diseases and maybe a new valuable treatment option for refractory BP. To report a case of refractory BP successfully treated with tofacitinib, then explore the underlying mechanism behind the treatment, and finally review similarities to other cases reported in the literature. Case report and literature review of published cases of successful BP treatment with JAK inhibitors. The case report describes a 73-year-old male with refractory BP that was successfully managed with the combination therapy of tofacitinib and low-dose glucocorticoids for 28 weeks. Immunohistochemistry and RNA sequencing were performed to analyze the underlying mechanism of tofacitinib therapy. A systematic literature search was conducted to identify other cases of treatment with JAK inhibitors. Throughout the 28-week treatment period, the patient experienced clinical, autoantibody and histologic resolution. Immunohistochemical analysis showed tofacitinib significantly decreased the pSTAT3 and pSTAT6 levels in the skin lesions of this patient. RNA sequencing and immunohistochemical testing of lesion samples from other BP patients identified activation of the JAK-STAT signaling pathway. Literature review revealed 17 previously reported cases of BP treated with four kinds of JAK inhibitors successfully, including tofacitinib (10), baricitinib (1), upadacitinib (3) and abrocitinib (3). Our findings support the potential of tofacitinib as a safe and effective treatment option for BP. Larger studies are underway to better understand this efficacy and safety.
Project description:BackgroundPhospholipase-associated neurodegeneration (PLAN) caused by PLA2G6 mutations is a recessively inherited disorder with three known phenotypes: the typical infantile onset neuroaxonal dystrophy (INAD); an atypical later onset form (atypical NAD); and the more recently recognized young-onset dystonia-parkinsonism (PLAN-DP).Case reportWe report the clinical, radiological, and genetic findings of a young Pakistani male with PLAN-DP. We review 11 previously published case reports cited in PubMed, and summarize the demographic, clinical, genetic, and radiological data of the 23 patients described in those articles.DiscussionPLAN-DP presents with diverse motor, autonomic, and neuropsychiatric features and should be considered in the differential diagnosis of patients with young-onset neurodegenerative disorders.
Project description:Hemophagocytic lymphohistiocytosis (HLH) is rare and life threatening syndrome. There are only a few reported cases of HLH with GI symptoms. We describe the case of an 18 months old boy who presented with a history of fever for 40 days, abdominal distention and hepatosplenomegaly. Abdominal x-ray showed a pneumoperitoneum. Urgent laparotomy was done which revealed an isolated cecal perforation. The histopathological findings in the subsequent resected bowel was HLH with evidence of positive EBV Barr infection.
Project description:PLA2G6-dystonia-parkinsonism (PLAN-DP) is characterized by levodopa responsive parkinsonism and dystonia. While neuropsychiatric symptoms and early cognitive decline are also common in this entity there is little information regarding other non-motor symptoms (NMS). Here, we describe a 26-year-old patient with PLAN-DP whose motor symptoms were preceded by mild cognitive impairment and anxiety, and who developed many other NMS as the disease evolved. Furthermore, we reviewed the NMS described in all the PLAN-DP patients published to date. A total of 50 patients with PLAN-DP were identified, 42 of whom developed NMS and in 23 of these cases, NMS preceded the motor symptoms of the disease. Neuropsychiatric symptoms dominated the premotor phase of this condition and cognitive impairment/dementia was the most prevalent NMS. Other NMS were reported infrequently like sleep disorders, autonomic symptoms, pain and hyposmia, and mostly as the disease evolved. NMS are very frequent in PLAN-DP and they may appear before diagnosis or during the course of the disease. Neuropsychiatric symptoms and cognitive decline are the most frequent NMS. The appearance of neuropsychiatric symptoms like depression, anxiety or personality changes prior to a diagnosis of parkinsonism in younger individuals might suggest the presence of PLA2G6 gene mutations.
Project description:BackgroundDural arteriovenous fistula (dAVF) rarely presents with a syndrome of reversible parkinsonism and rapidly progressive dementia, which has been described in 19 patients to date. However, its presenting features, pathophysiology, and response to treatment have not been reviewed.MethodsWe report the clinical course and treatment of two novel patients with this syndrome.ResultsDespite severe presentations, both patients recovered fully after fistula obliteration.ConclusionsAtypical parkinsonism with early cognitive changes and other focal neurological signs, along with features such as pulsatile tinnitus or worsening headache, should raise the possibility of dAVF. When treated, this syndrome is nearly always reversible, highlighting the importance of early diagnosis.
Project description:Pulmonary artery pseudoaneurysm (PAP) is a rare vascular phenomenon with a high mortality rate, as these entities can enlarge, rupture, and lead to asphyxiation. Pulmonary mucormycosis (PM), an underdiagnosed but an increasingly seen entity in the era of chemotherapy and immunosuppression, is a known cause of PAP, and should be suspected in immunosuppressed patients with hemoptysis. We present a case of PAP due to PM in a patient with recently diagnosed diffuse large B-cell lymphoma of the liver who underwent chemotherapy and developed acute cavitary lung disease and hemoptysis. His diagnosis was delayed due to the withholding of iodinated contrast with computer tomography (CT) imaging in the setting of renal failure. He then underwent embolization of his PAP with resolution of his hemoptysis. PAP is an uncommon cause of hemoptysis that can be diagnosed with CT pulmonary angiography, and mucormycosis is a known but rare cause of PAP in patients with malignancy receiving immunosuppression.
Project description:Herein we report the case of a 10-year-old boy with an autosomal mosaic mutation who developed bacteremia. The causative agent was identified as Moraxella osloensis by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and 16S rRNA gene sequencing. In the pediatric population, there have been 13 case reports of infection attributed to M. osloensis and this is the fifth reported case of pediatric bacteremia due to M. osloensis. After Moraxella species infection was confirmed, the patient recovered with appropriate antimicrobial therapy. It is important to consider that M. osloensis can cause serious infections, such as bacteremia, in otherwise healthy children.
Project description:We report a case of a 55 years old women who present a ALK associated renal cell carcinoma, with 3p deletion and measling of TFE3 expression. With CGH analysis and FISH we identify the rearrangment of ALK with TPM3