Side effects of the cold: how low temperatures can make some conditions worse

Not everyone likes winter. For people who do not enjoy the cold weather, or having to put on a thick coat to go outside, a winter can be a source of discomfort. Even healthy people are more susceptible to coughs and colds in winter, as colder temperatures can lower immunity, but for people with certain conditions, in particular autoimmune disorders, the cold can worsen their symptoms or cause additional symptoms. Common disorders such as arthritis and asthma may be worse in winter, while some rarer conditions, such as cryoglobulinema, are brought on by the cold. We will take a closer look at this in this article.

You can read about how we feel cold, what happens in our bodies when we feel cold, and why it is important to feel cold in our article: The genetics of feeling cold – Do Inuit feel the cold differently to other people?

Overview of the effects of cold temperatures

Cold temperatures can:

• Trigger symptoms of an existing disease: e.g., asthma, autoimmune angioedema, hyperkalemic periodic paralysis, hypokalemic periodic paralysis, psoriasis
• Cause disease (often secondary to an underlying condition): cold agglutinin disease, cryoglobulinemia, primary Raynaud phenomenon
• Cause Raynaud phenomenon as one of the disease symptoms: e.g., systemic lupus erythematosus
• Cause cold intolerance or increased sensitivity to cold: e.g., Hashimoto’s thyroiditis

Raynaud phenomenon

Also called Raynaud disease, Raynaud phenomenon occurs when cold temperatures or strong emotions cause blood vessels in the fingers and toes (sometimes also ear and nose) to narrow and restrict blood flow. This causes the skin to turn white and then blue; skin returns to its normal color when blood flow is restored [1].

Primary Reynaud phenomenon occurs without clear cause, while secondary Raynaud phenomenon is associated with another disorder or condition, many of which are discussed in the following sections.

Raynaud phenomenon is often a symptom of the following conditions:

• Autoimmune disorders: inflammatory myositis, scleroderma, Sjögren syndrome, systemic lupus erythematosus and rheumatoid arthritis
• Buerger disease
• Cold agglutinin disease
• Cryoglobulinemia
• Thoracic outlet syndrome

Some medications, especially those that narrow arteries, repetitive use injuries, smoking and frostbite can also cause Raynaud phenomenon [2]. Severe cases of Raynaud phenomenon can lead to gangrene [1].

Genetic disorders triggered by cold temperatures

Several genetic disorders are triggered by cold temperatures. While certain factors can be controlled, such as diet and medications, in an effort to manage the disorder/prevent attacks, unfortunately, the cold is not one of them.

Hyperkalemic periodic paralysis

Hyperkalemic periodic paralysis is a genetic disorder caused by changes in the SCN4A gene that affects around 1 in 200 000 people. It usually begins in childhood when attacks of extreme muscle weakness occur in response to a variety of triggers that include eating potassium-rich foods, stress, tiredness, fasting, certain medications, and cold temperatures. Levels of potassium in the blood are high during an attack [3, 4].

Hypokalemic periodic paralysis

Hypokalemic periodic paralysis is a genetic disorder caused by changes in the SCN4A or CACNA1S that affects around 1 in 100 000 people gene. Similar to hyperkalemic periodic paralysis, attacks of extreme muscle weakness occur in response to a variety of triggers that include eating a carbohydrate-rich meal, licorice, stress, exercise, certain medications, and cold temperatures. Levels of potassium in the blood are low during an attack [3, 5].

Nakajo-Nishimura syndrome

Also called autoinflammation-lipodystrophy-dermatosis (ALDD) syndrome or proteasome-associated autoinflammatory syndrome, this rare genetic disorder is reported predominantly in a small number of Japanese patients [6, 7]. One of the first symptoms, with an onset in infancy or early childhood, is red, swollen lumps or nodules on the skin that usually occur in cold weather [6]. Nakajo-Nishimura syndrome is caused by loss of function variants in the PSMB8 gene, which is important for the formation of immunoproteasomes, essential components of the immune system involved in recognizing objects foreign to the body’s immune system. Without immunoproteasomes, the immune system does not function correctly, which can lead to some of the disease symptoms [6, 7].

Disorders with a possible genetic cause and the effect of cold temperatures

There are many disorders without a proven genetic cause but where a genetic link is suspected, and some of these may also be worse in cold weather.

Arthritis

There are several types of arthritis, of which the most common is osteoarthritis. Around 40 to 65% of osteoarthritis cases have a genetic component, and a person is more likely to develop it if family members have it. Osteoarthritis develops when cartilage in a joint, particularly hands, hips, and knees, breaks down, causing pain, inflammation, stiffness, and a decreased motion [8, 9]. These pains are often worse in winter, and many sufferers can predict the onset of cold weather by an increase in pain [9]. See also rheumatoid arthritis.

Asthma

Asthma is a common illness that often runs in families. A polygenic, multifactorial genetic link is suspected, meaning that scientists have not identified a single gene that is responsible for causing it, but instead believe that multiple genes interact with each other and environmental factors to contribute to its development [10]. For many asthma sufferers, cold weather may irritate the airways and act as a trigger for an asthma attack [11].

Autoimmune disorders

Autoimmune disorders are caused by problems with the body’s immune system that causes it to attack healthy tissue as if it were harmful to the body. There are over 80 autoimmune disorders with varying effects and symptoms, and it is possible to suffer from more than one. It is unclear why some people develop autoimmune disorders, but there may be genes or genetic changes that make their development more likely [12]. The symptoms of certain autoimmune disorders can be triggered by cold weather, while other autoimmune disorders include Raynaud phenomenon in response to the cold as one of the symptoms.

Autoimmune angioedema

For sufferers of autoimmune angioedema, exposure to the cold can trigger an attack of the swelling, called edema, of lower skin layers of the face, lips, tongue, limbs, or genitals that characterizes this condition. Swelling of the tongue and upper airways can be life-threatening [13].

Cold agglutinin disease

This autoimmune disorder is caused by a type of antibody called agglutinins, which are produced by the immune system and circulate in the blood, and are activated by cold temperatures. When activated, they cause red blood cells to clump together and ultimately be destroyed. This leads to (hemolytic) anemia and other symptoms. Primary cold agglutinin disease without known cause usually starts around the age of 50, while secondary cold agglutinin disease is associated with infections and certain types of cancer. Cold-reacting agglutinins are activated when blood is exposed to temperatures of 0°C (32°F) to 10°C (50°F). Therefore, people with this condition must ensure they keep warm at all times [14, 15].

Cryoglobulinemia

Cryoglobulins are proteins in the blood that may clump together at temperatures below 37°C (98.6°F), causing inflammation and blocking and damaging blood vessels. Symptoms include purpura (skin lesions), joint pain, peripheral neuropathy (numb fingers and toes), and glomerulonephritis (kidney inflammation) which can lead to kidney failure. It is usually associated with chronic inflammatory disease (such as an autoimmune disease like systemic lupus erythematosus or rheumatoid arthritis), certain cancers or infection, especially with hepatitis C [16, 17]. However, genetic and/or environmental factors are thought to contribute to disease development in some patients [18]. Similar to cold agglutinin disease, patients should avoid cold exposure, especially of fingers and toes, where possible [16, 17].

Hashimoto’s thyroiditis

Also called chronic thyroiditis or Hashimoto’s disease, this autoimmune disease affects the thyroid gland in the neck and leads to reduced thyroid function. It is associated with a range of symptoms, including an increased sensitivity or intolerance to cold [19].

Mixed connective tissue disease

The symptoms of mixed connective tissue disease overlap with other autoimmune disorders that affect skin and connective tissue, e.g., scleroderma and systemic lupus erythematosus. Raynaud phenomenon is an early symptom of the disease; other symptoms include swollen fingers or hands and muscle and joint pain [20].

Psoriasis

Another condition that often runs in families is the autoimmune disorder, psoriasis. There are different types of psoriasis affecting different parts of the body, but all have skin symptoms, including the development of patches of thick, red, scaly, itchy skin or pus-filled blisters [21]. Psoriasis is common on the scalp, elbows and knees, and the inflammation present in the body may cause pain and stiffness in the joints called psoriatic arthritis [22]. Like asthma, psoriasis is a polygenic and multifactorial disease, and changes in genes that have a role in the functioning of the immune system are likely to be involved. In particular, genes of the human leukocyte antigen (HLA) complex are thought to be involved in the development of psoriatic arthritis and changes in the genes IL36RN and CARD14 that are involved in regulating inflammation increase the risk of developing a type of psoriasis called generalized pustular psoriasis [22, 23]. Cold weather can be a trigger for attacks of psoriasis due to less sunlight, hot dry air inside, and more illness [24].

Scleroderma

The autoimmune disorder scleroderma is characterized by the thickening or hardening of skin. In the localized form, only one area of skin (usually on the chest or abdomen) is affected, while in the systemic form, larger areas of skin (as well as organs and sometimes blood vessels) are involved. The lining of the esophagus may be affected, calcium may be deposited under the skin, and the skin of fingers, hands, forearms, and face is often stiff and tight. Raynaud phenomenon of fingers and toes is often seen in response to cold in people with scleroderma [25].

Sjögren syndrome

Dry eyes and mouth are the most common symptom of this autoimmune disorder; however, a wide range of other symptoms including Raynaud phenomenon, fatigue, pain and irregular heartbeats are seen. It often occurs together with another autoimmune disease [26].

Systemic lupus erythematosus

Often just called lupus, this autoimmune disorder usually causes joint pain and swelling and a butterfly-shaped rash over the cheeks and the bridge of the nose, as well as fatigue, fever, headaches, chest pain, and many other symptoms depending on the affected body part. Another common symptom is Raynaud phenomenon [27].

Rheumatoid arthritis

Like arthritis, rheumatoid arthritis is associated with pain, inflammation, and stiffness in the joints, but in this case, it is caused by attacks from the body’s own immune system. For some people, changes in temperature can cause their rheumatoid arthritis to flare-up [28].

Non-genetic diseases and the effect of cold temperatures

Buerger disease

Also called thromboangiitis obliterans, Buerger disease occurs when small blood vessels, particularly in the hands and feet, become inflamed and blocked. This leads to extreme pain, thrombosis, skin ulcers and even gangrene resulting in amputations. Raynaud phenomenon is also seen. Buerger disease is most common among heavy smokers [29].

Chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) causes breathing difficulties and shortness of breath, and some people with COPD find the cold exacerbates these problems [11].

Cold urticaria

This is a skin reaction to cold air or cold water. On exposure to cold, the skin develops itchy welts known as hives. This can be a mild skin reaction, or a severe whole body reaction (called anaphylaxis) which can be fatal. The cause is unknown, but it is more likely to occur if there is another existing health condition or a family history [30].

Respiratory disease

No discussion about cold weather and illness would be complete without mentioning colds (rhinovirus), flu (influenza virus), and other respiratory diseases caused by viruses, which peak in winter. These viruses are typically spread by inhaling droplets found in the air (e.g., when someone sneezes), but can also live for a short time on skin or other surfaces, and can be passed on after touching a contaminated surface and then your own mouth or nose. One reason respiratory viruses peak in winter is an increased rate of transmission as people spend more time indoors in less ventilated areas. Furthermore, it is possible these viruses reproduce more efficiently at the lower temperatures found in the nasal cavity in winter (caused by breathing in colder air) than at warmer temperatures. Another factor is that cold weather may affect the body’s immune response, making people more susceptible to the viruses [31].

Conclusion

For most people cold temperatures are an inconvenience or a cause of mild discomfort at worst, but for some, cold temperatures can cause illness or exacerbate existing conditions. These people will need to take measures to limit their exposure to the cold, wear appropriate clothing in cold temperatures, and take any supplements or medication necessary to prevent or control worsening of symptoms. As there is an increase in cases of respiratory disease in winter, everyone should be encouraged to adopt a lifestyle that supports health and well-being, including a healthy diet and exercise, and have flu and Covid vaccinations if recommended to do so by a healthcare provider.

The content of this article is for informational purposes only and is not intended to replace medical advice. Please visit your healthcare provider if you have concerns about your health and well-being.

References

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