Inflammation and immunology
C. Simon Herrington in Muir's Textbook of Pathology, 2020
Autoimmune diseases are common and may be either organ specific or systemic (Box 4.1). They result from the breakdown of tolerance, generation of an autoimmune response, and subsequent tissue damage. The autoimmune response may be humoral, cell mediated, or more commonly both. Generally, autoimmune diseases are due to a combination of both inherited and environmental factors. The best characterized genetic predisposition is the genotypic variation in HLA genes that encode MHC proteins. For example, the HLA-B27 genotype is associated with a substantially increased risk of developing conditions such as ankylosing spondylitis. Although the exact mechanisms for this are not yet fully elucidated, the pathogenic effects of HLA B27 are thought to be a result of MHC proteins having increased affinity for bacterial or ‘self’ proteins that activate cytotoxic T cells. An alternative theory is that HLA B27 results in MHC misfolding inducing cellular stress and a pro-inflammatory response. In either circumstance it is the difference in HLA genotype that contributes to the development of disease.
Diagnosis of IBD
Peter Sagar, Andrew G. Hill, Charles H. Knowles, Stefan Post, Willem A. Bemelman, Patricia L. Roberts, Susan Galandiuk, John R.T. Monson, Michael R.B. Keighley, Norman S. Williams in Keighley & Williams’ Surgery of the Anus, Rectum and Colon, 2019
Axial arthropathies are less frequent than peripheral arthropathies in patients with IBD.127 Axial arthropathy includes sacroiliitis and ankylosing spondylitis which are usually independent of the intestinal IBD activity. Patients with ankylosing spondylitis (mainly HLA-B27-positive) often experience severe onset of back pain at young age, usually associated with morning stiffness or pain exacerbation by periods of rest and at night. Physical examination reveals limited spinal flexion and reduced chest expansion. The disease course is usually progressive, resulting in permanent skeletal damage. It is diagnosed on conventional rheumatological grounds, and the diagnosis is supported by characteristic radiological changes; magnetic resonance imaging being the most sensitive (demonstrate inflammation before bone lesions occur).132 The treatment is frequently initiated by rheumatologists. Irrespective of the presence of inflammatory back pain, isolated radiographic sacroiliitis (mainly HLA-B27-negative) has been found in more than 25%132,133 which usually does not progress to ankylosing spondylitis.
Answers
Andrew Schofield, Paul Schofield in The Complete SAQ Study Guide, 2019
Ankylosing spondylitis is typically seen in young adult males and presents insidiously with low back pain and morning stifihess, and the majority of patients test positive for HLA-B27. Many cases progress to cause thoracic kyphosis and hyperextension of the neck, giving the classical ‘question mark’ posture. NSAIDs are commonly used for pain, exercise programmes are available to ensure posture and mobility are maintained and prolonged rest is not advised. Other management options include intra-articular injections and joint replacement surgery in severe cases. There are numerous extra-articular associations also, including aortic regurgitation, pulmonary fibrosis, anterior uveitis and amyloidosis.
Aggressive Initial Presentation of HLA-B27 Uveitis in Older Individuals: A Case Series
Published in Ocular Immunology and Inflammation, 2018
Preethi S. Ganapathy, Careen Y. Lowder, Sunil K. Srivastava
An 80-year-old African American male with a past medical history significant for end-stage renal disease on dialysis, hypertension, diabetes, and a history of uncomplicated cataract surgery in the right eye 4 months previously, presented with acutely decreased vision and pain in the right eye. Vision was count fingers in the right eye and intraocular pressure was 45 mmHg. He was noted to have a conjunctival injection, an epithelial defect with 1 mm infiltrate, and 2 mm hypopyon (Figure 1A). Examination of the left eye was normal. The patient underwent diagnostic corneal culture, anterior chamber paracentesis, and intravitreal injection of vancomycin and ceftazidime for possible infectious etiologies. He was also placed on oral acyclovir and topical intraocular pressure-lowering drops. Viral corneal culture was negative and anterior chamber paracentesis was negative. Laboratory testing revealed that the patient was positive for the HLA-B27 polymorphism. Subsequent computed tomography (CT) of the chest was negative for hilar adenopathy. He was treated aggressively with prednisolone acetate 1% for 4 weeks with improvement in vision to 20/20. Topical steroids were slowly tapered thereafter. At 1-year follow-up, there were no recurrences of ocular inflammation.
Ankylosing Spondylitis Patients with HLA-B*2704 have More Uveitis than Patients with HLA-B*2705 in a North Chinese Population
Published in Ocular Immunology and Inflammation, 2018
Haibo Li, Qiuxia Li, Chen Ji, Jieruo Gu
Uveitis is considered the most frequent extra-articular manifestation in AS. It has been found in 5.3–33.2% of HLA-B27-positive AS patients across different racial groups.12 It has already been proven that occurrence of uveitis is higher in HLA-B27-positive AS patients compared with those negative for HLA-B27. However, as to the relationship between subtypes of HLA-B27 and uveitis, the results are conflicting. Some studies have indicated that HLA-B*2705-positive patients appear to be more closely associated with uveitis than HLA-B*2704;5,6 a result opposite to our study. Consistent with our study, Chavan et al.4 reported that uveitis was observed more frequently in HLA-B*2704-positive AS patients than in HLA-B*2705-positive AS patients in an Indian population, but it did not have statistical differences. Park et al.3 and Lee et al.7 reported that there was no significant difference in the presence of uveitis between HLA-B*2704- and HLA-B*2705-positive AS patients in a Korean population. There are several reasons which may explain these conflicting results.
Trabecular bone score value is associated with new bone formation independently of fat metaplasia on spinal magnetic resonance imaging in patients with ankylosing spondylitis
Published in Scandinavian Journal of Rheumatology, 2020
KY Kang, J-Y Jung, SK Lee, HK Min, YS Hong, S-H Park, JH Ju
Clinical assessments and human leucocyte antigen (HLA)-B27 status were investigated at baseline. Height and weight were measured at the time of the spinal MRI and DXA measurements, and were used to calculate body mass index (BMI). C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (16) were assessed at the time of baseline spinal MRI and DXA examinations. Clinical examinations at 2 year follow-up were performed at the same time as radiographic assessment. Medications were also recorded, including non-steroidal anti-inflammatory drugs (NSAIDs), sulfasalazine, and tumour necrosis factor (TNF) inhibitors. Sustained users were defined as those patients who had taken treatment agents for periods of 1 year or longer. No patient received systemic glucocorticoids.
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