Overview

The general conception of symptoms caused by viral infections are coughing, runny nose, fever and pneumonia, however, some patients may have also experienced severe joint pain and reduced joint flexibility. This is known as arthritis, a chronic inflammatory disease that occurs in joints in the knees and fingers. Adenoviruses, a subclass of respiratory viruses, also seem to play a role in this development of arthritis.

Arthritis is a broad term that describes inflammatory joint pain, with a vast range of subtypes, including osteoarthritis, rheumatoid arthritis, psoriatic arthritis, gout and many more. Such arthritic conditions have different causes and treatment methods, therefore the influence of adenovirus also differs depending on the type of arthritis. Broadly speaking, viral infections can directly induce arthritis (known as viral arthritis) or increase the risk of primary rheumatological diseases (such as rheumatoid arthritis and gout).^1,2  Although its precise mechanism is still unknown, it is thought that adenovirus promotes arthritis by stimulating chronic inflammation, cell death and autoreactivity of immune cells.³

Adenovirus

Transmission and infection

Similarly to other respiratory viruses, adenovirus infection can take place through the following routes:⁴

• Sneezing
• Coughing
• Touching hands or objects with a virus particle on the surface, and touching mouth, nose or eyes without washing hands

Common symptoms

Symptoms of adenovirus are similar to flu and other respiratory viral infections. Appropriate antiviral therapy is usually sufficient for recovery within a few days/weeks. However, patients with an immunodeficiency can experience more severe and extensive symptoms.⁵

Common symptoms may include:⁶

• Fever and cold
• Sore throat
• Coughing
• Inflammations in the stomach/intestines (gastroenteritis)

Severe cases of adenovirus could include a range of diseases, including conjunctivitis, cystitis, myocarditis, cardiomyopathy and meningoencephalitis.⁷

Arthritis

Causes of arthritis

As mentioned before, the cause of arthritis depends on its type. Even so, each of their mechanisms is highly complicated, resulting in an exhaustive list of genetic and environmental factors that contribute to arthritic conditions.

Genetic factors

• Mutations of genes involved in immunity, especially those that regulate/prevent autoimmunity, are considered to increase the risk of arthritis greatly. Essentially, autoimmunity is the misidentification of self-antigens, cells and tissues as harmful substances by host immunity
• Different types of arthritis have varying female-to-male ratios^8,9 

Environmental Factors

• Smoking stimulates cell death in the lungs, which triggers inflammation. It can also increase the production of self-antigens in rheumatoid arthritis
• Injuries – post-trauma metabolic alterations and inflammatory responses at synovial joints can stimulate chronic immune responses. This is known as post-traumatic arthritis¹⁰
• Changes in the microbiome.
• Viral and other microbial infections such as bacteria can cause inflammation.
• Build up of circulating uric acid in gout. 

Symptoms of Arthritis

Arthritis is associated with a broad range of symptoms including:¹¹

• Joint pain
• Joint stiffness
• Joint deformation
• Emotional lability
• Fatigue
• Skin warmth and swelling
• Sleep deprivation

How adenovirus triggers viral arthritis

What is viral arthritis?

Viral arthritis is distinctively different from primary rheumatological diseases such as rheumatoid arthritis and osteoarthritis. This is because viral arthritis is specifically induced by viral infections, whereas  primary rheumatological diseases are caused by other factors such as trauma, smoking and genetic defects. With that said, it is worth noting that viral infections can increase the risk of such rheumatological diseases too, which will be further discussed later.

The most major type of viral arthritis is called acute onset polyarticular arthritis which at most lasts for a few weeks. Viral arthritis is more likely to occur in adults compared to children. In comparison  to rheumatoid arthritis or osteoarthritis, viral arthritis is also known to be relatively milder.²

Mechanism of viral arthritis

A broad range of respiratory viruses can trigger arthritis, including parvoviruses, hepatitis, HIV and papillomaviruses.^3,19 Additionally, the inflammatory symptoms caused by such viruses are diverse, including immune complex formation and chronic inflammation.² For such reasons, it is very difficult to differentiate arthritic conditions that are caused by different respiratory viruses, while understanding the precise mechanism of viral arthritis in general is also facing major obstacles. Therefore, the distinctive and accurate mechanism of adenovirus-induced viral arthritis is yet to be fully understood.

Nonetheless, we can still try to understand how adenovirus induces arthritis, based on the general pathophysiology of viruses:² 

• Molecular mimicry – Viral antigens can mimic host antigens. Its similar molecular structure to host antigens triggers an immune response against host cells
• Epitope spreading – Host cells damaged by viral infections release self-antigens. The circulating self-antigens are picked up by immune cells, resulting in autoimmunity
• Bystander activation – Viral invasion causes inflammation which is accompanied by increased cytokine release. This activates T cells that react to self-antigens 

Research is also limited because the number of adenovirus-induced arthritis is very low compared to parvoviruses and hepatitis.³ Adenovirus is more frequently associated with respiratory and gastrointestinal manifestations, rather than arthritic conditions.³ With that said, a small number of case studies have shown that adenovirus-induced arthritis seems to occur in patients with agammaglobulinemia, or deficiency of antibodies, as well as certain microbial infections.¹² 

Links to other arthritic conditions

Rheumatoid arthritis

Rheumatoid athritis is an autoimmune condition, where immune cells detect self-proteins (self-antigens) as foreign, which stimulates tissue damage at joints including bone erosion and cartilage damage. 

The number of cases of rheumatoid arthritis and viral infections has similar seasonal tendencies, where the maximum and minimum number of cases for both are observed during July and December respectively, suggesting a possible relationship between the two.¹

Self-antigens in rheumatoid arthritis are self-proteins that have been citrullinated (conversion of the amino acid arginine in a protein into the amino acid citrulline) d following cell death.¹³ This is a natural occurrence, however, people with genetic mutations can have immune cells that are reactive against these otherwise harmful citrullinated proteins. Cell death is increased by smoking, bacterial infections and respiratory viruses. The damaged cells release citrullinated proteins, which are detected by immune cells, leading to autoimmunity.

As an example, a case study of a 9-year-old girl showed that adenovirus can cause juvenile rheumatoid arthritis.¹⁴ 

Gout

Gout is a chronic inflammatory disease resulting in joint pain in the lower limb.¹⁵ A significant risk factor of gout is high uric acid levels in circulating blood which is stimulated in infections of respiratory viruses.¹⁶

Psoriasis

Psoriasis is an autoimmune inflammatory condition associated with joint pain, joint enlargement, reduced range of movement and muscle wasting.^17,18   

Similarly to rheumatoid arthritis, viral infections are thought to increase the risk of psoriasis, although adenoviral infection occurs less frequently compared to HIV or papillomaviruses.¹⁹ More significantly, anti-adenovirus vaccines have shown some relation to psoriasis, although at a very low incidence.²⁰ The precise mechanism of vaccine-induced psoriasis is unknown, but it is likely to do with elevated activity of T cells.²⁰ It is worth noting that vaccine effectiveness is unaltered in patients with psoriasis.²⁰ 

Summary

Adenovirus infection can directly cause viral arthritis or increase the risk of primary rheumatological diseases. Although adenovirus-induced arthritis is rare, case studies and comparisons with other respiratory viruses show that adenoviruses can alter immune responses to cause autoimmunity and chronic inflammation. Rheumatoid arthritis, gout and psoriasis are all examples of primary rheumatological diseases that adenoviruses could potentially play a role in. However, in either case, the complexity of arthritic conditions and diverse subclasses of viruses make it difficult to understand the precise role and mechanism of adenovirus in the development of arthritis. 

FAQs

What treatment methods can be taken for viral arthritis?

In general, immunosuppressive drugs such as non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids are used for treating symptoms of viral arthritis.^2,21Analgesics can also be used to reduce joint pain, however, it is important to understand that this does not remove the underlying cause of arthritis.

Immunosuppressive drugs can increase the risk of opportunistic microbial infections, therefore their use must be limited and tightly regulated. Although it was previously mentioned that vaccines can potentially cause psoriasis, vaccination is still a useful therapeutic method to prevent viral arthritis and avoid opportunistic infections.¹⁹

Arthritis caused by autoimmunity such as rheumatoid arthritis and psoriasis can potentially be treated with haematopoietic stem cell therapy. This replaces stem cells that carry mutations with a high risk of autoimmunity.

How to find out if you have viral arthritis?

A viral infection causes viral arthritis, therefore it is likely that the patient experiences typical flu-like symptoms associated with viral infections such as fever, fatigue and a cough.

Clinics can conduct a blood test that detects antibodies to determine the type of virus causing the arthritic condition.