The risk/benefit ratio of glucocorticoid therapy can be improved by proper use. Careful monitoring and using appropriate preventive strategies can potentially minimize side effects.

Proteoglycans are important components of cell plasma membranes and extracellular matrices of connective tissues. They consist of glycosaminoglycan chains attached to a core protein via a tetrasaccharide linkage, whereby the addition of the third residue is catalyzed by galactosyltransferase II (β3GalT6), encoded by B3GALT6. Homozygosity mapping and candidate gene sequence analysis in three independent families, presenting a severe autosomal-recessive connective tissue disorder characterized by skin fragility, delayed wound healing, joint hyperlaxity and contractures, muscle hypotonia, intellectual disability, and a spondyloepimetaphyseal dysplasia with bone fragility and severe kyphoscoliosis, identified biallelic B3GALT6 mutations, including homozygous missense mutations in family 1 (c.619G>C [p.Asp207His]) and family 3 (c.649G>A [p.Gly217Ser]) and compound heterozygous mutations in family 2 (c.323_344del [p.Ala108Glyfs(∗)163], c.619G>C [p.Asp207His]). The phenotype overlaps with several recessive Ehlers-Danlos variants and spondyloepimetaphyseal dysplasia with joint hyperlaxity. Affected individuals' fibroblasts exhibited a large decrease in ability to prime glycosaminoglycan synthesis together with impaired glycanation of the small chondroitin/dermatan sulfate proteoglycan decorin, confirming β3GalT6 loss of function. Dermal electron microcopy disclosed abnormalities in collagen fibril organization, in line with the important regulatory role of decorin in this process. A strong reduction in heparan sulfate level was also observed, indicating that β3GalT6 deficiency alters synthesis of both main types of glycosaminoglycans. In vitro wound healing assay revealed a significant delay in fibroblasts from two index individuals, pointing to a role for glycosaminoglycan defect in impaired wound repair in vivo. Our study emphasizes a crucial role for β3GalT6 in multiple major developmental and pathophysiological processes.

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Rituximab achieved a high rate of disease control in PUK patients with GPA and is the preferred agent in halting disease progression.

Objective: This paper reviews ocular pain with the main focus on ocular surface discomfort and dry eye pain. Anatomy, physiology, epidemiology, assessment, and treatment are discussed in this paper. Methods: A PubMed search was conducted for studies published from 2000 to 2019 on the anatomy, pathophysiology, epidemiology, assessment, and treatment of ocular pain. Reviews, meta-analyses, and randomized clinical trials were included. Inclusion criteria focused on ocular surface discomfort, dry eye pain and neuropathic pain. Results: A total of 112 articles were found through searches, 45 of which were selected and studied in this review. Discussion: Pain in general can be acute or chronic. Acute pain is usually a physiologic response to a serious damage to the tissues and alleviates with pain relief treatments. Chronic pain is defined as the persistence of pain for more than three months. From another point of view, pain has been classified into either nociceptive or neuropathic. Nociceptive pain is a physiologic response to a noxious stimulus. Both central and peripheral nervous systems can be involved in the development of a neuropathic pain, which is characterized by positive or negative sensory signs, a pain perceived disproportionate to a noxious stimulus, and/or not responsive to analgesics. Chronic pain usually has a neuropathic component. Ocular surface pain is a well-known complaint after any corneal surgery. This is mainly due to abnormal regeneration of damaged corneal nerve endings and abnormal connections with adjacent nerve endings which produce spontaneous activity. Tear hyperosmolarity and the resultant ocular surface inflammation can also trigger voluntary activity of corneal nerve endings. Referral pain to the first and second division of the trigeminal nerve has been reported. Interference with vision and even sleep, which is out of proportion to the examination are among patients' complaints. All of these elements proposed the new concept of ocular neuropathic pain syndrome. The first step in conventional evaluation of ocular discomfort is search for tear insufficiency. Pathologies of lid and blinking as well as conjunctival irregularities should be addressed. Anti-inflammatory agents and, in resistant cases, systemic neuromodulators are shown to be helpful. Education on behavioral changes and reassurance are essential steps. Considering the neuropathic origin for the ocular pain, treatment modalities used for such pain in other parts of the body can be considered for this syndrome.

The seronegative spondyloarthropathies are a group of autoimmune inflammatory diseases lacking rheumatoid factor or antinuclear antibody in their serum. They include ankylosing spondylitis (AS), reactive arthritis, psoriatic arthritis, spondylitis associated with Crohn’s disease and ulcerative colitis, and undifferentiated spondyloarthropathies. Inflammation mostly affects the axial joints, entheses, and extra-articular structures such as uveal tract, gastrointestinal tract, mucocutaneous tissue, and heart. Uveitis is the most common extra-articular manifestation. Spondyloarthropathies, especially AS, have a strong association with the presence of Human Leukocyte Antigen (HLA)-B27 gene. AS happens earlier in HLA-B27 patients and men are more prone to the disease. Uveitis, typically unilateral nongranulomatous acute anterior uveitis, occurs in up to 50% of the patients with AS. HLA-B27 positivity correlates with more frequent flare-ups. Conjunctivitis and scleritis are rare ocular manifestations of AS. To establish the diagnosis of AS, at least one clinical and one radiologic parameter are required for definitive diagnosis. Magnetic resonance imaging (MRI) or bone scan can help early detection of the axial skeleton inflammation. The course of eye and joint involvement are not correlated. Short-term treatment with topical corticosteroids and cycloplegic agents control the uveitis attack. In resistant cases, local or systemic therapy with corticosteroids are recommended. NSAIDs, disease-modifying anti-rheumatic drugs (DMARDs), methotrexate, azathioprine, anti-IL-17A monoclonal antibodies, and TNF- α antagonists are effective treatments for ocular and systemic manifestations of AS. If not treated adequately, uveitis may become recalcitrant and extend posteriorly. Functional impairment due to joint destruction can also occur as a result of undertreatment.

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