Made by DATEXIS (Data Science and Text-based Information Systems) at Beuth University of Applied Sciences Berlin
Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
Funded by The Federal Ministry for Economic Affairs and Energy; Grant: 01MD19013D, Smart-MD Project, Digital Technologies
Uveitis may be an immune response to fight an infection inside the eye. While representing the minority of patients with uveitis, such possible infections include:
- brucellosis
- leptospirosis
- Lyme disease
- presumed ocular histoplasmosis syndrome
- syphilis
- toxocariasis
- toxoplasmic chorioretinitis
- tuberculosis
- Zika fever
Uveitis is usually an isolated illness, but can be associated with many other medical conditions.
In anterior uveitis, no associated condition or syndrome is found in approximately one-half of cases. However, anterior uveitis is often one of the syndromes associated with HLA-B27. Presence of this type of HLA allele has a relative risk of evolving this disease by approximately 15%.
The most common form of uveitis is acute anterior uveitis (AAU). It is most commonly associated with HLA-B27, which has important features: HLA-B27 AAU can be associated with ocular inflammation alone or in association with systemic disease. HLA-B27 AAU has characteristic clinical features including male preponderance, unilateral alternating acute onset, a non-granulomatous appearance, and frequent recurrences, whereas HLA-B27 negative AAU has an equivalent male to female onset, bilateral chronic course, and more frequent granulomatous appearance. Rheumatoid arthritis is not uncommon in Asian countries as a significant association of uveitis.
Several aetiologies are suggested, and any combination of these may be present in any given case.
- Vitamin deficiency (A, B or C)
- Viral infection
- Bacterial infection
- "Leptospira
- "Streptococcus
- "Brucella
- Parasitic infection
- Strongyle
- "Onchocerca cervicalis"
- Autoimmune disease
The disease has been suggested to be primarily autoimmune in nature, being a delayed hypersensitivity reaction to any of the above agents.
The Appaloosa has a higher risk of developing ERU than other breeds; this predisposition has a genetic basis. Appaloosas which develop ERU are more likely than other breeds to have ERU in both eyes, and more likely to become blind in one or both eyes.
Serpiginous choroiditis, also known as geographic or helicoid choroidopathy, is an uncommon chronic progressive inflammatory disease affecting adult men and women equally in the second to seventh decades of life.
Although intermediate uveitis can develop at any age, it primarily afflicts children and young adults. There is a bimodal distribution with one peak in the second decade and another peak in the third or fourth decade.
In the United States the proportion of patients with intermediate uveitis is estimated to be 4-8% of uveitis cases in referral centers. The National Institutes of Health reports a higher percentage (15%), which may indicate improved awareness or the nature of the uveitis referral clinic. In the pediatric population, intermediate uveitis can account for up to 25% of uveitis cases.
ARN is associated with people who have latent herpes viruses that have been reactivated. The most common causes of the disease have been linked to VSV, HSV-1, HSV-2, and CMV respectively.
ARN cases have been reported in patients who have AIDS, are immunocompromised and in children. The disease is not limited to a specific gender. Most cases have been reported in young adults though children and the elderly can be affected.
Specific genetic markers in Caucasians in the United States have shown elevated risk for disease development (HLA-DQw7 and Bw62, DR4) as well as HLA-Aw33, B44, and DRw6 in the Japanese population.
Pars planitis is considered a subset of intermediate uveitis and is characterized by the presence of white exudates (snowbanks) over the pars plana or by aggregates of inflammatory cells in the vitreous (snowballs) in the absence of an infectious or a systemic disease. Some physicians believe that patients with pars planitis have worse vitritis, more severe macular edema, and a guarded prognosis compared to other patients with intermediate uveitis.
In this condition the posterior uveitis shows a geographic pattern. The inflammation begins in the juxtapapillary choroid and intermittently spreads centrifugally. The overlying retinal pigment epithelium and the outer retina are involved in the inflammatory process.
A closely related condition is multifocal serpiginoid choroiditis. This is caused by tuberculosis.
The distinction between these two conditions is important as the latter responds to anti tuberculosis treatment while the former does not.
With Behçet's disease as an intercurrent disease in pregnancy, the pregnancy does not have an adverse effect on the course of Behçet's disease and may possibly ameliorate its course. Still, there is a substantial variability in clinical course between patients and even for different pregnancies in the same patient. Also, the other way around, Behçet's disease confers an increased risk of pregnancy complications, miscarriage and Cesarean section.
Behçet's can cause male infertility, either as a result of the condition itself or of a side effect of concomitant medication such as Colchicine, which is known to lower sperm count.
Herpes zoster ophthalmicus (HZO) and also known as ophthalmic zoster is a disease characterised by reactivation of dormant varicella zoster virus residing within the ophthalmic nerve (the first division of the trigeminal nerve). This condition is an important subtype of shingles, representing 15% of all cases.
Herpes zoster ophthalmicus is transmitted via direct contact or droplets. Varicella zoster virus is a DNA virus which produces acidophilic intranuclear inclusion bodies. The virus is neurotrophic in nature.
The frontal nerve is more commonly affected than the nasociliary nerve or lacrimal nerve.
Chorioretinitis is often caused by toxoplasmosis and cytomegalovirus infections (mostly seen in immunodeficient subjects such as people with HIV or on immunosuppressant drugs). Congenital toxoplasmosis via transplacental transmission can also lead to sequelae such as chorioretinitis along with hydrocephalus and cerebral calcifications. Other possible causes of chorioretinitis are syphilis, sarcoidosis, tuberculosis, Behcet's disease, onchocerciasis, or West Nile virus. Chorioretinitis may also occur in presumed ocular histoplasmosis syndrome (POHS); despite its name, the relationship of POHS to "Histoplasma" is controversial.
In a study done published by the British Journal of Ophthalmology, the cases of ARN/BARN reported in 2001-2002 in the UK, Varicella Zoster Virus was the most common culprit for the disease and presented mostly in men than in women.
Researchers have also looked at two cases of ARN in patients who have been diagnosed with an immunodeficiency virus. The disease presented itself more so in the outer retina until it progressed far enough to then affect the inner retina. The patients were not so responsive to the antiviral agents given to them through an IV, acyclovir specifically. The cases progressed to retinal detachment. The patients tested positive for the herpes virus. Researchers are now wondering if this type of ARN is specific to those who have the immunodeficiency virus.
Although there is sometimes a preceding viral infection, or skin or eye trauma, the exact underlying initiator of VKH disease remains unknown. However, VKH is attributed to aberrant T-cell-mediated immune response directed against self-antigens found on melanocytes. Stimulated by interleukin 23 (IL-23), T helper 17 cells and cytokines such as interleukin 17 (IL-17) appear to target proteins in the melanocyte.
Affected individuals are typically 20 to 50 years old. The female to male ratio is 2:1. By definition, there is no history of either surgical or accidental ocular trauma. VKH is more common in Asians, Latinos, Middle Easterners, American Indians, and Mexican Mestizos; it is much less common in Caucasians and in blacks from sub-Saharan Africa.
VKH is associated with a variety of genetic polymorphisms that relate to immune function. For example, VKH has been associated with human leukocyte antigens (HLA) HLA-DR4 and DRB1/DQA1, copy-number variations (CNV) of complement component 4, a variant IL-23R locus and with various other non-HLA genes. HLA-DRB1*0405 in particular appears to play an important susceptibility role.
Congenital syphilis is that which is transmitted during pregnancy or during birth. Two-thirds of syphilitic infants are born without symptoms. Common symptoms that develop over the first couple of years of life include enlargement of the liver and spleen (70%), rash (70%), fever (40%), neurosyphilis (20%), and lung inflammation (20%). If untreated, late congenital syphilis may occur in 40%, including saddle nose deformation, Higoumenakis sign, saber shin, or Clutton's joints among others. Infection during pregnancy is also associated with miscarriage.
Chorioretinitis is usually treated with a combination of corticosteroids and antibiotics. However, if there is an underlying cause such as HIV, specific therapy can be started as well.
A 2012 Cochrane Review found weak evidence suggesting that ivermectin could result in reduced chorioretinal lesions in patients with onchocercal eye disease. More research is needed to support this finding.
The syndrome is rare in the United States, Africa and South America, but is common in the Middle East and Asia, suggesting a possible cause endemic to those tropical areas. A theory suggested that past exposure to lethal infectious agents might have fixed the genetic susceptibility factors to Behçet's disease in those area. It is not associated with cancer, and links with tissue-types (which are under investigation) are not certain. It also does not follow the usual pattern for autoimmune diseases. However, one study has revealed a possible connection to food allergies, particularly to dairy products. An estimated 15,000 to 20,000 Americans have been diagnosed with this disease. In the UK, it is estimated to have about 1 case for every 100,000 people. Globally, males are affected more frequently than females. In the United States, more females are affected than males.
In an epidemiologic study, 56 percent of patients with Behçet's disease developed ocular involvement at a mean age of 30. Ocular involvement was the first manifestation of Behçet's disease in 8.6 percent of patients. Ocular Behçet's disease with involvement of the optic nerve is rarely reported. Among patients with ocular Behçet's disease funduscopic findings of optic atrophy, and optic disc paleness have been identified with a frequency of 17.9 percent and 7.4 percent, respectively. Other fundoscopic findings include vascular sheathing (23.7%), retinal hemorrhage (9%), macular edema (11.3%), branch retinal vein occlusion (5.8%), and retinal edema (6.6%). However, optic atrophy was the most significant cause of visual impairment identified in 54 percent of patients with ocular Behçet's disease and permanent visual impairment.
The prevalence of this disease increases from North to South. It follows a more severe course in patients with an early age of onset particularly in patients with eye and gastrointestinal involvement.
Scleritis is not a common disease, although the exact prevalence and incidence are unknown. It is somewhat more common in women, and is most common in the fourth to sixth decades of life.
Anterior uveitis develops in 40–50% of cases with HZO within 2 weeks of onset of the skin rashes. Typical HZO keratitis at least mild iritis, especially if Hutchinson's sign is positive for the presence of vescicles upon the tip of the nose.
Features:
This non-granulomatous iridocyclitis is associated with:
- Small keratic precipitates
- Mild aqueous flare
- Occasionally haemorrhagic hypopion.
HZO uveitis is associated with complications such as iris atrophy and secondary glaucoma are not uncommon. Complicated cataract may develop in the late stages of the disease.
"Acute bacterial parotitis:"
is most often caused by a bacterial infection of Staphylococcus aureus but may be caused by any commensal bacteria.
"Parotitis as Extrapulmonary Tuberculosis:"
The mycobacterium that cause tuberculosis can also cause parotid infection. Those infected tend to have enlarged, nontender, but moderately painful glands. The diagnosis is made by typical chest radiograph findings, cultures, or histologic diagnosis after the gland has been removed. When diagnosed and treated with antitubercular medications, the gland may return to normal in 1–3 months.
"Acute viral parotitis (mumps):"
The most common viral cause of parotitis is mumps. Routine vaccinations have dropped the incidence of mumps to a very low level. Mumps resolves on its own in about ten days.
"HIV parotitis:" Generalized lymphadenopathy has long been associated with HIV, but the localized enlargement of the parotid gland is less well known.
Birdshot chorioretinopathy is a rare form of posterior uveitis and accounts for 1-3% of uveitis cases in general. Birdshot chorioretinopathy is thought to be an autoimmune disease. The disease has strong association with the Human leukocyte antigen haplotype (HLA)-A29, which is the strongest association between a disease and HLA class I documented (>99% of patients are HLA-A29 positive by molecular testing and HLA-A29-negative cases are controversial). This indicates a role for T-lymphocytes in the pathogenesis. Birdshot chorioretinopathy is associated with IL-17, a hallmark cytokine of TH17 cells that play an important role in autoimmunity . The disease affects typically middle-aged or elderly caucasians. HLA-A29 is less prevalent in Asia and no birdshot chorioretinopathy cases have been reported in Asia. When birdshot chorioretinopathy is suspected, a person is usually tested to determine if they are HLA-A29 positive. Although previously HLA-A29 testing was not considered necessary for definitive diagnosis, because HLA-A29 is also common in the general healthy population (7%). An increasing number of specialists consider the presence of HLA-A29 critical for diagnosis. Additional (genetic or environmental) or unknown factors may be associated with HLA-A29 in the pathogenesis.
In 2014, Kuiper et al. conducted a genome-wide association study in birdshot chorioretinopathy and studied the entire genome of Dutch, Spanish and English patients. This large genetic study ascertained HLA-A29:02 as the primary risk factor and identified the "endoplasmic reticulum aminopeptidase (ERAP) 2" gene strongly associated with birdshot chorioretinopathy. Genetic variants near "ERAP2" on chromosome 5 resulted in high mRNA and protein expression of this aminopeptidase in BSCR patients. ERAP2 is an aminopeptidase that, together with the closely related ERAP1, trims peptides in the endoplasmic reticulum and loads these peptides on HLA molecules for presentation to T cells of the immune system. ERAP-HLA associations have also been reported in Ankylosing spondylitis and Behcet's disease, suggesting shared pathogenic pathways among these diseases.
Episcleritis is a common disease, and its exact prevalence and incidence are unknown. It typically affects young adults, and may be more common in women.
The CDC recommends that sexually active men who have sex with men be tested at least yearly. The USPSTF also recommends screening among those at high risk.
Syphilis is a notifiable disease in many countries, including Canada the European Union, and the United States. This means health care providers are required to notify public health authorities, which will then ideally provide partner notification to the person's partners. Physicians may also encourage patients to send their partners to seek care. Several strategies have been found to improve follow-up for STI testing, including email and text messaging as reminders of appointments.
These are also collectively known as chronic punctate parotitis or chronic autoimmune parotitis.
"Sjögren's syndrome:"
Chronic inflammation of the salivary glands may also be an autoimmune disease known as Sjögren's syndrome. The disease most commonly appears in people aged 40–60 years, but it may affect small children. In Sjögren syndrome, the prevalence of parotitis in women versus men is approximately 9:1. The involved parotid gland is enlarged and tender at times. The cause is unknown. The syndrome is often characterized by excessive dryness in the eyes, mouth, nose, vagina, and skin.
"Lymphoepithelial lesion of Godwin:"
Most frequently associated with a circumscribed tumor with the histologic features of Sjögren syndrome. This designation has also fallen out of favour.