COVID-19 News: Researchers Warn COVID-19 Infections And COVID-19 Vaccines Can Trigger Onset Of Vogt-Koyanagi-Harada Disease That Can Cause Blindness!

COVID-19 News: Vogt-Koyanagi-Harada (VKH) is a rare multisystem inflammatory disease affecting the eyes, ears, brain, skin, and hair. The Coronavirus Disease 2019 (COVID-19) is a new contagious infection that might trigger the onset of VKH disease, as previously proposed for other viruses. Moreover, after the mass vaccination against SARS-CoV-2 worldwide, cases of VKH disease associated with COVID-19 vaccination have been reported. Researchers from Sapienza University of Rome, Italy presents an overview of VKH and all the VKH cases described after COVID-19 infection and vaccination. No differences have been found considering epidemiology and clinical findings of the disease compared to those reported in the no-COVID era. All of the patients promptly responded to systemic and local corticosteroid therapy with a good final visual prognosis. Different possible pathogenetic mechanisms underlying the onset of VKH after COVID-19 vaccination are discussed, while the presence of the HLA DR4 antigen as a genetic predisposition for the onset of the disease after COVID-19 infection and vaccination is proposed. VKH disease is one of the most frequently reported uveitic entities after COVID-19 vaccination as covered in numerous cases reports and COVID-19 News coverages, but a good response to therapy should not discourage vaccination. Nevertheless, ophthalmologists should be alerted to the possibility of VKH occurrence or relapse after COVID-19 vaccination, especially in genetically predisposed subjects.


 
VKH Disease, COVID Infection And COVID-19 Vaccines
As of August 2023, there were 768,983,095 cases of COVID-19 and 6,953,743 deaths since the start of the COVID-19 pandemic. SARS-CoV-19 is a single-stranded RNA virus with the largest known RNA genome. It is a spherical virion with an envelope consisting of phospholipids and proteins that surround the central capsid. SARS-CoV-2 belongs to the beta-coronavirus group, which also includes MERS-CoV and SARS-CoV. Beta-coronaviruses have three essential proteins in the pericapsid: the spike protein (S), the membrane protein (M), and the envelope protein (E).
 
Protein S mediates virus adhesion to the cell membrane receptor, membrane fusion, and viral entry into the host cell. Protein M and protein E are part of the membrane structure of the coronavirus. Another component of the beta-coronavirus is the N protein, which is a component of the helical nucleocapsid. The spike protein of SARS-CoV-2 demonstrates an affinity for the ACE-2 receptor, which facilitates the cellular entry of SARS-CoV-2 into the host cells and represents the critical target for vaccine development.
 
Cases of VKH disease after a COVID-19 infection have been described, suggesting that the SARS-CoV-2 virus is a possible trigger for VKH, as previously proposed for other viruses such as hepatitis B, hepatitis C, CMV, and EBV.
 
It has been found that the mean time that elapsed between COVID-19 infection and VKH symptoms was 19.75 ± 6.57 days, and the median was 17.5 days. Most of the patients were women, which is consistent with women having more robust immune responses to infections than men. The therapy used was oral steroids in all cases, with the addition of topical steroids for two cases and intravenous steroids for two cases.
 
The association between vaccines and VKH has been reported in the literature with many types of vaccines, such as hepatitis B, influenza, yellow fever, and tuberculosis vaccines. A proposed mechanism of VKH disease after vaccination was the administration of adjuvants in genetically susceptible individuals.
 
VKH disease is a bilateral, diffuse granulomatous uveitis mediated by autoimmune targeting and the destruction of melanocytes. It also involves other anatomical structures that contain melanocytes, causing neurological, audiovestibular, and dermatological changes. Genetic susceptibility has been reported to be closely associated with the HLA class II antigen, HLA-DR4. VKH disease is one of the most frequently reported uveitis entities after vaccination, and it also appears after COVID-19 infection.
 
A close relationship between VKH disease and microbial infection has also been reported, with EBV, CMV, influenza A virus, mycoplasma pneumonia, and TB being the supposed etiologic or inducing factors.
 
Molecular mimicry is a possible explanation for the relationship between both COVID-19 infection and vaccination. Molecular mimicry occurs when an element of a vaccine shares antigenic features with the host, causing an immune response against the foreign antigen to also damage host cells with similar surface antigens. It's important to note that all VKH patients in the study carried the HLA-DR4 antigen, indicating a possible genetic predisposition for VKH onset or recurrence after COVID-19 vaccination.
 
Understanding Vogt-Koyanagi-Harada Disease: Causes, Symptoms, Diagnosis, and Treatment
Vogt-Koyanagi-Harada (VKH) disease is a rare and complex autoimmune disorder that can affect multiple systems within the body, including the eyes, ears, brain, skin, and hair.
 
Epidemiology of VKH Disease
VKH disease exhibits some interesting epidemiological patterns. It is more commonly found in individuals of pigmented races, including Asians, Middle Easterners, Hispanics, and Native Americans. Conversely, VKH disease is sporadic in Africa and relatively infrequent in Europe. Women are more frequently affected than men, and the onset of the disease typically occurs between the second and fifth decades of life. However, pediatric cases and late-onset cases have also been reported.
 
Understanding the Pathogenesis
VKH disease is classified as a T-cell autoimmune disease characterized by an immune response against choroidal melanocytes. These melanocytes express class II major histocompatibility complex (MHC) antigens, particularly antigens associated with the enzyme tyrosinase, which plays a role in melanin synthesis. A strong association has been established between VKH disease and specific MHC class II genes, most notably the HLA-DR4 gene. This genetic association has been observed across various ethnic groups, including North American, Korean, Japanese, Italian, Hispanic, Chinese, and Indian populations.
 
Clinical Features of VKH Disease
VKH disease manifests through distinct clinical stages, each characterized by specific clinical features:
 
Prodromal Stage: This initial stage typically lasts for 3 to 5 days and presents with nonspecific symptoms such as malaise, fever, nausea, headache, meningismus (neck stiffness), dizziness, and orbital pain. Neurological symptoms like cranial nerve palsies, hemiparesis, transverse myelitis, and optic neuritis may also occur during this stage. Patients may report photophobia, tearing, and hypersensitivity of the hair and scalp.
 
Acute Uveitic Stage: Following the prodromal phase, the acute uveitic stage emerges, lasting several weeks. Patients commonly experience blurred vision, pain, and central scotomas. Bilateral posterior uveitis is a hallmark, with signs including thickening of the posterior choroid, hyperemia, optic disc edema, and circumscribed retinal edema.
 
Chronic (Convalescent) Stage: This stage can persist for months to years and is marked by integumentary changes, including vitiligo, poliosis (loss of pigmentation in hair), and alopecia.
 
Chronic Recurrent Stage: Characterized by recurrent anterior granulomatous uveitis, this stage is often resistant to corticosteroid therapy and may lead to complications such as glaucoma, cataracts, neovascularization, subretinal fibrosis, and subretinal neovascularization.
 
Extra-Ocular Manifestations
VKH disease is not limited to ocular involvement; it can also affect other systems within the body. Extraocular manifestations may include:
 
Integumentary System: Patients may experience hypersensitivity of the hair and scalp, poliosis (whitening of hair or eyelashes), alopecia (hair loss), and vitiligo (loss of skin pigmentation).
 
Central Nervous System: Neurological symptoms can manifest as sterile meningitis (neck stiffness, headache), encephalitis (seizures, altered consciousness), and cranial neuropathies, including ocular motility disturbances.
 
Auditory System: Inner ear problems may occur, leading to symptoms such as tinnitus, deafness, and vertigo.
 
Diagnosis of VKH Disease
Diagnosing VKH disease can be challenging due to the absence of a single definitive test. Diagnosis typically relies on a combination of clinical features and either systemic or ocular findings. Several sets of criteria have been proposed over the years to aid in diagnosis, including those by Sugiura, the American Uveitis Society (AUS), and the Standardization of Uveitis Nomenclature (SUN) Working Group.
 
Treatment Approaches
The primary goal in managing VKH disease is to suppress intraocular inflammation, particularly in the acute posterior uveitic/exudative stage. High-dose systemic corticosteroid therapy is often the initial treatment choice and has shown efficacy in many cases. However, treatment should be initiated promptly, ideally within two weeks, to reduce disease duration and complications.
 
Prognosis and Factors Influencing Outcomes
The prognosis of VKH disease has improved significantly with advances in treatment. Several factors have been correlated with the final visual prognosis of VKH patients, including timely treatment, duration of treatment, initial visual acuity, complications, and the number of relapses.
 
Conclusion
Vogt-Koyanagi-Harada disease is a complex autoimmune disorder that affects multiple organ systems, primarily the eyes, and can result in significant morbidity if not properly managed. Timely diagnosis and treatment with high-dose corticosteroids, often combined with immunosuppressive agents, have significantly improved patient outcomes. Recent research has also highlighted potential associations between VKH disease and viral infections, including COVID-19, as well as COVID-19 vaccinations. These emerging areas of investigation underscore the ongoing complexity of VKH disease and the need for further research to elucidate its triggers and pathogenesis.
 
The study findings were published in the peer reviewed Journal of Clinical Medicine.
https://www.mdpi.com/2077-0383/12/19/6242
 
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