Rheumatology: Current Research
Open Access

Immunosuppressive Therapy and the Risk of Herpes Zoster in Rheumatoid Arthritis

Yannis Alamanos^{* *}Correspondence: Yannis Alamanos, Department of Rheumatology, University of Ioannina, Ioannina, Greece, Email:

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About the Study

Rheumatoid Arthritis (RA) is an autoimmune disorder that affects millions of individuals worldwide, leading to chronic inflammation and progressive joint damage. The treatment regimen for RA often includes immunosuppressive therapy, which can significantly impact the patient's susceptibility to infections. Among these infections, Herpes Zoster (HZ), commonly known as shingles, poses a particular risk due to its potential to cause severe pain and complications.

Pathophysiology of herpes zoster

Herpes zoster is caused by the reactivation of the Varicella-Zoster Virus (VZV), the same virus that causes chickenpox. After an initial infection with chickenpox, VZV remains dormant in the dorsal root ganglia of the nervous system. Various factors can trigger the reactivation of the virus, leading to herpes zoster. The reactivation is most commonly associated with weakened immune function, which can be a result of aging, stress, or medical treatments that suppress the immune system.

Immunosuppressive therapy in rheumatoid arthritis

The goal of immunosuppressive therapy in RA is to reduce inflammation, alleviate pain, and prevent joint damage. Various classes of drugs are used to achieve these outcomes, including Disease-Modifying Antirheumatic Drugs (DMARDs) and biologics. Traditional DMARDs like methotrexate and sulfasalazine, as well as biologic agents such as Tumor Necrosis Factor (TNF) inhibitors, Interleukin-6 (IL-6) inhibitors, and Janus Kinase (JAK) inhibitors, all contribute to immune suppression but through different mechanisms.

Methotrexate is one of the most widely used DMARDs and acts as an anti-inflammatory and immunosuppressive agent. It inhibits the metabolism of folate, which is need for DNA synthesis and cell proliferation.

Biologics target specific cytokines involved in the inflammatory process. For instance, TNF inhibitors such as infliximab and adalimumab block TNF-α, a cytokine that plays a significant role in the inflammatory response. While these agents reduce the disease activity in RA, they can also impair immune responses to pathogens, including VZV.

JAK inhibitors are a newer class of drugs that inhibit enzymes involved in the signaling pathways of the immune system. Agents like tofacitinib and baricitinib are effective for controlling inflammation but can have significant immunosuppressive effects.

Risk of herpes zoster in RA patients on immunosuppressive therapy

RA patients undergoing immunosuppressive therapy have an increased risk of developing herpes zoster compared to the general population. The suppression of the immune system can lead to a decreased ability to contain VZV in the dorsal root ganglia, thus facilitating its reactivation.

Studies have shown that patients on methotrexate alone have a moderately increased risk of herpes zoster, with the risk being higher when combined with other immunosuppressive drugs. When combined with biologic agents such as TNF inhibitors, the risk increases significantly.

The introduction of JAK inhibitors has further complicated the risk assessment. While these drugs are effective in reducing RA symptoms, they are associated with a significant risk of herpes zoster.

Clinical manifestations of herpes zoster in RA patients

The clinical presentation of herpes zoster in RA patients is similar to that in the general population. The initial symptoms typically include localized pain, tingling, or itching, followed by the appearance of a vesicular rash that follows the distribution of a dermatome. However, in RA patients, the severity can be amplified due to their compromised immune status.

One of the most common complications of herpes zoster in RA patients is Postherpetic Neuralgia (PHN), a condition characterized by persistent pain in the area affected by the rash. PHN can have a significant impact on a patient's quality of life, leading to chronic pain that may require additional treatment strategies.

Implications for patient care

Managing the risk of herpes zoster in RA patients undergoing immunosuppressive therapy requires a multi-faceted approach. Early recognition of symptoms and timely treatment with antiviral medications can help reduce the severity and duration of the infection. Antiviral drugs like acyclovir, valacyclovir, and famciclovir are commonly prescribed to reduce the viral load and mitigate complications.

The role of vaccination is significant, though this falls under prevention strategies, which were excluded from the scope of this article. The Zoster vaccine has been shown to reduce the incidence of herpes zoster and its complications in immunocompetent adults, but its use in immunocompromised patients must be carefully considered due to potential safety concerns.

Impact on treatment plans

The risk of herpes zoster can influence the choice and management of immunosuppressive therapies. Physicians may need to adjust treatment plans, considering the potential risks and benefits for individual patients. This may involve using the lowest effective dose of immunosuppressive agents, carefully monitoring for early signs of herpes zoster, and considering alternative therapies when appropriate. Collaborating with infectious disease specialists can be beneficial in creating a comprehensive treatment strategy for RA patients at risk of herpes zoster.

Herpes zoster is a significant risk for RA patients undergoing immunosuppressive therapy, particularly when using drugs that impact immune function such as methotrexate, TNF inhibitors, and JAK inhibitors. These therapies, while effective in controlling RA symptoms and preventing joint damage, can compromise the body's ability to control latent VZV.