Systemic lupus erythematosus (SLE) is an autoimmune condition where the body attacks its own cells throughout the body, leading to a wide range of symptoms.
SLE is well known to affect women and minorities disproportionately. 78% of people with autoimmune disease are female, and of those, about 90% of people with lupus are female.
However, this doesn’t mean that people of all genders and all ethnic groups can’t get lupus! Men are an understudied group when it comes to lupus and autoimmune diseases in general. Why are these numbers so different?
An autoimmune disease is when the body’s own immune system malfunctions and starts attacking its own cells without reason. Autoimmune diseases rely on the immune systems of the patients, so anything that affects their immune system also impacts their lupus. Biological sex and gender expression both have an affect on the conditions that effect the immune system.
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Biological Sex and Lupus
The immune system appears to act differently in men (biologically male people) versus women (biologically female people.) In particular, they respond with different “helper T cells,” which are the activator molecules for the cells that fight viruses. Women generally have a stronger T cell response than men, and more robust immune systems in general. However, because T cells normally attack the body’s own cells to stop viral infections, it only takes a few things to go wrong before this stronger immune response attacks healthy cells, too. It’s unclear how the different helper T cells that are activated in men and women change the very complex immune system, but researchers have noticed that there is an age difference in lupus symptom onset along with this cell activation difference. Hormone levels and the immune system itself change across a person’s lifespan, so a natural shift in how the immune system is functioning might be a trigger for lupus: In men, this means that they tend to show symptoms of autoimmune disease before age 50. In women, it tends to be later in life.
Research estimates that approximately 1 in 10 people with lupus are male. Lupus in men have the same symptoms but are even less likely to be diagnosed properly due to misinformation. Doctors also have a tendency to “look for horses, not zebras” even when said zebra is right in their face. Discrimination is a factor, too, and many men are dismissed or are pressured by society to ‘man up’ and ‘muscle through’ their pain.
Genetic background plays a huge role in the development of lupus, as does environmental stress. Both of these could contribute to why people of African, Asian, Hispanic/Latino, Native American, Native Hawaiian, and Pacific Islander descent are more likely to develop lupus. A difference in hormone levels may be responsible for the different rates of lupus between the sexes, with higher levels of estrogen in women being one of the reasons they are more susceptible to autoimmune disease (while also having stronger immune responses overall.) However, in men, genetic susceptibility built into their genes and high stress life situations could be enough to trigger lupus. This is not a guarantee – there have been many cases of identical twins where only one develops lupus.
Some possible other environmental exposures include traumatic situations (such as combat, natural disaster, or major life events including divorce, deaths in the family, or a high-stress job.) Exposure to chemicals, silica dust, ultraviolet radiation, viral infections, overexertion to the point of exhaustion, and even surgery. Anything that causes stress to the body and mind has the potential to trigger the series of events that lead to lupus developing.
Both men and women can have genes that predispose them to developing lupus. However, many of the genes for immune system regulation are on the X chromosome, possibly giving women a “double dose” of vulnerable genes if they inherit them.
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Sex Hormone Differences and Lupus
Hormones cause different effects on the immune system. Estrogen and progesterone are associated with higher immune system activity, while testosterone is associated with lower activity. More accurately, estrogen is an immune system modulator, meaning that it can ramp up or down the activity of the immune system.
If immune system cells are reacting improperly to estrogen (due to genes that change the receptor for estrogen, for example,) then the effects would be magnified in females versus males. Other hormones that regulate the immune system, such as prolactin and progesterone, are present at higher levels in females, as well. Some research implies that the vulnerability to autoimmune diseases is the flip side of the stronger immune systems and fiercer immune responses that females often have. The stronger immune response protects the body, but when regulation falls short and it starts targeting the body’s own cells, this is also made stronger and more damaging.
Notably, hormone therapies, including HRT for gender transitioning, can change the immune response – a small study reported that transgender women with lupus appeared to develop their lupus or saw their symptoms worsen after estrogen treatment. The one transgender man in the study also reported that his lupus symptoms improved with testosterone treatments.
However, many men with lupus do not have unusual levels of estrogen, and do not always have low testosterone levels. Males with lupus don’t have unusual sexual desire or performance (aside from fatigue and pain,) and their fertility isn’t always affected by lupus. Both can be lowered by certain lupus medications, however.
This points to the hormone differences not being a be-all end-all for developing lupus.
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Kidney Failure, Men, and Lupus
Both men and women have flares, and experience most of the same symptoms, including mouth and skin symptoms. SLE where multiple organs are effected at once is slightly more common in men.
Kidneys filter out extra fluid, salts, and waste products from the bloodstream, turning them into urine which is then removed from the body. Kidneys also manage hormones associated with the bloodstream and bone production, such as erythropoietin and calciferol (also known as vitamin D.)
Kidneys are vital for keeping the blood chemistry of the body balanced. When things start to go wrong in the kidneys, such as through lupus nephritis damage, waste products build up in the blood and effects the whole body. The fluid balance is also sent out of whack, leading to excess fluid leaking into the surrounding tissues and causing swelling. One kidney does enough work to take care of the body, meaning that, if the damage is noticeable, then both kidneys are affected. This is very frequent in lupus, as it attacks and damages both kidneys at the same time.
Kidney failure is defined as the kidneys being so damaged that they only work at 15% efficiency and can’t filter the blood properly. 15-20% of lupus cases lead to kidney failure even with treatment. Dialysis is a medical procedure that cleans the blood in the kidney’s place, but it requires frequent hospital visits to maintain. Some people are able to solve the problem more permanently, however, by getting a working kidney donated to pick up the slack.
Because a person can live without one kidney, it can be donated by a match (often a relative) with few complications outside of the operation. The kidney transplant itself usually takes 3-4 hours as the new kidney is connected up to the blood vessels and ureter. The old kidney is not removed, generally.
Other Reasons for Sex Differences and Lupus
Stress causes the body to go into survival mode, which can seriously strain and damage organs throughout the body. However, for people with lupus, the most frustrating aspect of stress is that it changes how the immune system functions, not only putting it on high alert to attack, but making it more likely to attack the body’s own cells and cause flares. In many cases, chronic stress is what causes lupus symptoms to emerge for the first time, leading to a person developing lupus. This can include studying, major life changes, and trauma of both the physical and psychological kind. Not only does stress lead to the development of lupus, but it can make the symptoms worse – which, of course, causes more stress and creates a feedback loop that is difficult to break. Stress, even from one’s childhood, is known to cause worse outcomes of lupus and be a risk factor for developing other conditions such as rheumatoid arthritis.
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Symptom Differences for Men: How Different Are They?
Some researchers believe that the differences in symptom intensity between men and women might actually be “selection bias.”
Because of societal expectations of masculinity, men often refuse to visit the doctor for a checkup unless heavily pressured to do so by a significant other, or when the symptoms are so severe that they have no choice. Many men feel uneasy about going to the doctor and, to them, admitting their symptoms is ‘weakness.’ It also takes time, and many men feel that going to the doctor is a low priority task – they could be doing something else in that time! Men (and women) sometimes don’t mention symptoms to their doctors because they aren’t ready to hear the diagnosis. It’s very complicated, but because of this, there are likely many men who are not diagnosed with autoimmune disorders such as SLE, among other conditions.
Psychologically, it is often difficult for men with lupus to come to terms with having a ‘women’s disease’ like lupus. The society we live in also puts a lot of emphasis on a man’s ability to work, in particular, to do physical labor or exercise. Not being able to do these things because of lupus can be very emotionally taxing. In addition to hair loss from lupus, embarrassment may be a major factor.
In addition, because lupus in men is rare, doctors will only diagnose it in men when the symptoms are intense enough for it to be clear that it is lupus. Kidney failure and neurological symptoms may be more common because they are the most noticeable and urgent symptoms of lupus, which can trigger a closer look by doctors in the know, which can lead to a diagnosis.
However, this does not account for all of the differences: For example, the age range that lupus is diagnosed is correlated with the natural fluctuation of estrogen and testosterone and the changes in immune activity that naturally occur over one’s lifespan.
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Diagnosing Men with Lupus
SLE is often diagnosed late in men, partially due to it being uncommon in men. SLE is normally caught at around 45-60 years of age, when the symptoms are at their highest point, compared to women where lupus is generally caught at 20-30 years.
Men with SLE are more likely to have serious cardiovascular issues, such as anemia and strokes, and to have neurological symptoms like seizures. There is also some evidence for kidney issues, as in lupus nephritis, being more intense in men, but researchers caution that the sample size is very small. Men with more kidney damage might be more likely to be diagnosed correctly, for example, or to feel sick enough to go to the doctor in the first place. Overall, though, the symptoms are the same.
Lupus in men can also show up as fatigue, pain, swelling, and headaches. It can also appear as cardiovascular issues (heart disease, stroke, anemia) serositis, kidney disease, and the classic malar rash. Some symptoms of lupus are more severe in men, particularly kidney damage.
If a man has these symptoms, then it’s a good idea to get an antinuclear antibody test (ANA) detects these antibodies, and is an important tool for diagnosing lupus in men and women. 97% of people with lupus have antinuclear antibodies detected, while 5-20% of people in the general population will register a positive.
An antinuclear antibody test doesn’t diagnose lupus on its own, but helps to confirm that lupus is a possibility, so it’s a good first or second step towards diagnosis.
Treating Men for Lupus
The treatment for lupus is the same for men as it is for women. The side effects of some medications may be different however – Cyclophosphamide, for example, has a side effect of potentially lowering sperm count.
The immunosuppressant medication Voclosporin might be especially important. Voclosporin is being specifically developed for people with lupus nephritis, because it is less likely to damage the kidneys further, while also preventing the symptoms of lupus.
In addition to medication, therapy might be especially important for men. Therapy provides a safe space to process emotions and mental traumas. Men often do not have such safe spaces available to them, or do not feel like they belong in such spaces. Healing the wounds of mental traumas not only reduces the stress that might trigger a lupus flare but helps people with lupus develop strategies and ways of thinking that may reduce the stress load of their lives.
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