Autoimmune diseases are the third most prevalent category of illness in the United States, behind cancer and heart disease, affecting an estimated 50 million people. The prevalence of autoimmunity is on the rise in the United States, with researchers finding a 44% increase in ANA, a common autoantibody in autoimmune disease, in the last 25 years. While autoimmune diseases are more commonly diagnosed in women, it’s important to recognize that men are not exempt, comprising approximately 20% of those affected. Diagnosing autoimmune diseases can be challenging, with an average diagnosis timeline of four (4) years. This challenge can be further compounded in men due to the misconception that autoimmune diseases are a women’s health issue and the fact they are more prone to avoid health care. A timely diagnosis allows for early therapeutic action to slow disease progression, reduce long-term damage, and avoid high healthcare costs. In this article, we will increase our understanding of male autoimmune disorders and approaches to diagnosis and treatment using functional medicine tests.
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What is The Immune System, and What is Autoimmunity?
A normal functioning immune system defends the body against foreign invaders. It is a complex network of cells, tissues, and molecules that work together to recognize and combat external threats. A fundamental characteristic of a properly functioning immune system is known as "self-tolerance,” which refers to its ability to distinguish between the body’s cells and tissues and foreign invaders or harmful substances. The recognition of the body’s components as “self” causes the immune system to avoid mounting an attack against them. When tolerance is lost, it can lead to autoimmune diseases, where the immune system mistakenly targets and damages the body’s own cells and tissues.
Autoimmune diseases are a diverse group of disorders that can affect virtually any body part, from joints and skin to vital organs. Signs and symptoms of autoimmune diseases will vary depending on which autoimmune disease has been diagnosed and which tissues and organs are affected. Some common symptoms include fatigue, joint pain and swelling, dizziness, muscle pain, sinus problems, digestive issues, recurring fever, and swollen glands. The exact cause of autoimmunity is not fully understood. Still, genetics, infections, and other environmental factors, such as dysbiosis and toxin exposure, are thought to play roles in triggering these disorders. Examples of autoimmune diseases with higher rates of diagnosis in men include ankylosing spondylitis (AS), rheumatoid arthritis (RA), type 1 diabetes, psoriasis, and primary sclerosing cholangitis (PSC).
Ankylosing Spondylitis: Not Just a Pain in the Back
Ankylosing Spondylitis (AS) is a type of arthritis characterized by inflammation of the spine. It commonly manifests as sacroiliitis: inflammation between the sacroiliac (SI) joints at the base of the spine where it meets the pelvis. It can extend to spondylitis, involving joints between the vertebrae. AS affects approximately 0.2-0.5% of the US population, with men being affected at a rate two times higher than women. 95% of AS patients carry a genetic mutation in the human leukocyte antigen-B gene (HLA-B), which also raises the risk of developing other autoimmune diseases like Crohn’s disease ulcerative colitis (UC). Symptoms typically arise between the ages of 17 and 45, characterized by persistent or intermittent low back or hip pain and stiffness. Additional manifestations may include pain and stiffness in other joints, fatigue, weight loss, and abdominal discomfort. AS can progress to limit spinal mobility, leading to spinal fusion, and can also result in complications like eye inflammation (uveitis), cardiovascular issues, and lung problems (2).
Diagnosing ankylosing spondylitis (AS) does not rely on a single definitive test but a combination of factors. Imaging, blood tests, and a thorough medical history review are all valuable tools in the diagnostic process. The Assessment of Spondyloarthritis International Society (ASAS) has established specific diagnostic criteria for AS, which include individuals having experienced persistent back pain for more than three months, being under the age of 45, and meeting one of two sets of criteria: either evidence of sacroiliitis on MRI along with one or more AS-related features, or being HLA-B27 positive and having two or more AS-related features. These features encompass inflammatory back pain, arthritis, enthesitis, uveitis, dactylitis, psoriasis, Crohn's disease, ulcerative colitis, a favorable response to non-steroidal anti-inflammatory drugs (NSAIDs), a family history of AS, the presence of HLA-B27 gene mutation, and elevated C-reactive protein (CRP).
AS is a chronic condition for which there is no cure. The primary objectives of treatment are to alleviate pain, minimize joint damage, and prevent long-term complications. Various treatment approaches include regular physical activity and physical therapy, non-steroidal anti-inflammatory drugs (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs) like sulfasalazine and biologics, corticosteroids, and, in certain cases, surgical interventions.
Rheumatoid Arthritis: Beyond the Joints
Rheumatoid arthritis (RA), the most common form of autoimmune arthritis, targets joint linings, causing painful swelling that can lead to bone erosion and joint deformities. In 2019, 18 million people worldwide were diagnosed with RA, 30% of which were men. The condition typically begins by affecting smaller joints, like fingers and toes, in a symmetrical pattern, causing tender, warm, swollen, and stiff joints that are worse in the mornings and after periods of inactivity. As the disease progresses, it can spread to larger joints such as the wrists, knees, ankles, elbows, hips, and shoulders. Symptoms usually emerge between ages 30 and 50 but can manifest at any point in life. Although the exact cause remains uncertain, genetics and age increase susceptibility. Environmental factors like obesity, alcohol consumption, smoking, toxic exposures (such as silica and asbestos), dysbiosis, and infection have been associated with its development.
RA is associated with potential complications such as joint deformities, joint erosion, and loss of function, which can significantly impact daily life. Moreover, RA is a systemic inflammatory disorder that can ultimately affect other organs and systems, including the heart, lungs, and blood vessels (37).
Early diagnosis and comprehensive treatment plans are crucial to effectively manage RA and minimize these complications. Diagnosis involves joint examination and blood tests, including rheumatoid factor (RF), anti-cyclic citrullinated peptide antibody (anti-CCP), sedimentation rate (ESR), and C-reactive protein (CRP). Treatment strategies include NSAIDs and corticosteroids for symptom relief and inflammation control. For more severe cases, DMARDs, like methotrexate and biologics, can be utilized. Physical therapy and exercise are essential for maintaining joint flexibility and strength (37).
As with other chronic conditions, men with RA have higher mortality rates than women. While RF prevalence is similar between genders, men tend to develop nodules more frequently, whereas women often exhibit more erosions. Recent evidence suggests that men may respond better to biologic treatments, achieving higher rates of early remission. However, this may be counterbalanced by an increased risk of adverse events, like severe infections, during treatment (31).
Male-Specific Challenges in Autoimmune Disorders
Sex differences in autoimmune diseases include variations in prevalence, clinical presentation, and disease progression. While the precise underpinnings of these disparities are not fully understood, several factors might contribute to gender distinctions in autoimmune conditions. Firstly, men and women experience different immune responses. T-helper cells, a subset of white blood cells, play a role in regulating the immune system and are divided into two main types: Th1 (T-helper type 1) and Th2 (T-helper type 2). Th1 cells predominantly oversee cell-mediated immunity, essential for combating intracellular pathogens, like viruses and specific bacteria, and producing proinflammatory cytokines.
In contrast, Th2 cells are responsible for humoral immunity, crucial for countering extracellular pathogens, such as parasites and allergens, and promoting antibody production. Women's immune systems tend to respond to challenges with increased antibody production, while men's responses are often characterized by heightened inflammation. Hormonal variations and divergent exposure to environmental factors can further influence disease risk and severity. Genetic factors, including chromosomal variances and susceptibility genes like HLA-B27, may also play a role in shaping these differences. Autoimmune diseases with a male predilection typically manifest before the age of 50, characterized by acute inflammation, the emergence of autoantibodies, and a proinflammatory Th1 immune response (20, 34).
Men living with autoimmune diseases often encounter unique challenges arising from differences in symptom presentation compared to women and the prevailing misconception that autoimmune disorders affect the female population (14, 23). Societal biases and stereotypes may also discourage men from seeking medical care or expressing vulnerability (35). Overcoming these stereotypes and increasing awareness about the diverse ways autoimmune diseases impact men is essential to ensure early diagnosis and access to appropriate treatment and support. Diagnosis of chronic and potentially debilitating conditions like autoimmune diseases can cause mental-emotional challenges for men, affecting their sense of masculinity, especially as they grapple with limitations in participating in physical activities and occupations they once took pride in (22).
Exploring Other Prevalent Autoimmune Diseases in Men
Within the broad spectrum of male autoimmune conditions, several other disorders warrant attention:
Primary Sclerosing Cholangitis
Primary sclerosing cholangitis (PSC) is an autoimmune disorder characterized by the attack and subsequent scarring of the bile ducts, resulting in backflow of bile into the liver and liver damage.PSC is diagnosed in males at a rate twice that of females, typically occurring between the ages of 30 and 40. Notably, 80% of patients with PSC are also diagnosed with inflammatory bowel disease (IBD).
Infections
Certain infections have been associated with an increased risk of developing an autoimmune disease. The Viral Screen by Immunosciences Lab, Inc. detects common infections from four significant viruses, including EBV, CMV, HSV-1, and HSV-2.
Adrenal Testing
Many individuals report high levels of stress before the onset of autoimmune diseases. The Adrenocortex Stress Profile by Genova Diagnostics measures hypothalamic-pituitary-adrenal (HPA) axis activity through multiple salivary measurements of cortisol and DHEA.
Autoantibody Testing
Autoantibodies may be present for years before the development of autoimmune diseases and can predict future risks. The Array 5 - Multiple Autoimmune Reactivity Screen by Cyrex Laboratories measures predictive antibodies for certain conditions for patients concerned about their future risk and wanting to prevent the development of autoimmune diseases.
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Summary
Autoimmune diseases represent a significant and growing health concern. It's a misconception that these conditions are only a concern for women, when in reality, they also impact men, accounting for at least 20% of the affected population. Overcoming the gender bias in diagnosis is essential, as early recognition is key to adequately managing these conditions and preventing long-term damage or complications. In this context, functional medicine testing can be an essential tool, enabling diagnosis and offering insight into the underlying factors contributing to autoimmune diseases. Such testing allows healthcare professionals to tailor treatment strategies to ensure better outcomes for both men and women grappling with these conditions.
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