Sweat is a clear, salty liquid produced by glands in your skin. Sweating is how your body cools itself. You sweat mainly under your arms and on your feet and palms. When sweat mixes with bacteria on your skin, it can cause a smell. Bathing regularly and using antiperspirants or deodorants can help control the odor.

Sweating a lot is normal when it is hot or when you exercise, are anxious, or have a fever. It also happens during menopause. If you often sweat too much, it's called hyperhidrosis. Causes include thyroid or nervous system disorders, low blood sugar, or another health problem.

Sweating too little, anhidrosis, can be life-threatening because your body can overheat. Causes of anhidrosis include dehydration, burns, and some skin and nerve disorders.

Introduction

Anhidrosis is the inability to sweat. It is important to recognize anhidrosis as it can be potentially life-threatening due to heat-related illnesses. There are three main causes of anhidrosis, which are peripheral alterations in the eccrine gland itself, idiopathic, and central or neuropathic disease and/or medication that disrupts neural inputs from the anterior hypothalamus to the gland.

Causes of central/neuropathic anhidrosis can occur at any level of innervation. The disturbance can occur at the sweating center in the brain, the descending neural tract, or the sweat gland. A disruption will lead to an absence of sweating. Disruption in the neural input can be due to tumors or infarctions of the hypothalamus, pons, or medulla. Spinal cord tumors, injuries, or infarctions can disrupt the neural tract. Other etiologies such as degenerative syndromes (Shy-Drager syndrome), autoimmune autonomic neuropathy, peripheral neuropathy (diabetes, alcohol use disorder, leprosy), and drugs have all been implicated in central/neuropathic anhidrosis.

Peripheral alterations that cause anhidrosis can be congenital or acquired. In addition, forms of peripheral alterations can be due to genetic abnormalities such as incontinentia pigmenti, due to local destruction, for example, by a tumor, or obstruction by entities such as psoriasis.

As heat intolerance may be due to various underlying disorders, a detailed history is important in establishing the diagnosis. Heat intolerance can cause drowsiness, episodic inability to concentrate while in a hot environment, or fatigue, along with a decrease in the patient's normal sweating, which are clues to the diagnosis of anhidrosis. A detailed history should also include the addition of medications, medical events such as injuries, growths or radiation, alcohol consumption, the presence of autoimmune disease or diabetes mellitus, and family history.

Causes

Central and neuropathic causes of anhidrosis can occur anywhere along the neural track, as previously stated. There are diagnostic clues that will aid in locating the area of the lesion. If there is the involvement of the pons or medulla, the patient will have ipsilateral facial and neck anhidrosis. Neural tracks in the spinal cord have both crossed and uncrossed fibers. Therefore, alterations in the spinal cord will result in anhidrosis of the skin that can be either ipsilateral or contralateral. Peripheral neuropathies tend to be symmetrical as in diabetes mellitus and alcohol use disorder. However, there are cases of asymmetrical peripheral neuropathy leading to anhidrosis, such as in cases of leprosy. A patient with Horner syndrome will present after the disruption of the superior cervical ganglion. Regional anhidrosis can also occur due to the chemical blockade of a selected sympathetic ganglion. Congenital insensitivity to pain with anhidrosis is a rare entity that is autosomal and recessive. It presents with self-mutilation due to a lack of pain, intellectual disability, and recurrent fevers due to anhidrosis.

Drugs that interfere with the synaptic transmission in the autonomic ganglia will lead to anhidrosis:

• Nicotinic acetylcholine receptor antagonists such as hexamethonium and trimethaphan

• Muscarinic acetylcholine receptor antagonists such as atropine or scopolamine

• Calcium channel blockers

• Alpha-adrenergic blockers such as phentolamine

• Alpha2-adrenergic agonists such as clonidine

• 5-fluorouracil

• Topiramate

• Zonisamide

• Quinacrine

There are numerous causes of abnormalities in the sweat gland that cause anhidrosis. Among the various causes are several hereditary and acquired systemic diseases that present with generalized or localized anhidrosis. Males with X-linked hypohidrotic ectodermal dysplasia will have an absence of sweat glands, whereas female carriers will have hypohidrosis or reduced sweating. The other ectodermal dysplasias, such as Rapp-Hodgkin syndrome and Naegeli-Franceschetti-Jadassohn syndrome, can lead to sweat gland abnormalities. Though not an exhaustive list, there are other rare inherited syndromes in which genetic errors result in sweat gland dysfunction such as Bazex-Dupre-Christol syndrome and Fabry disease.

Local tissue destruction can be the culprit of acquired localized anhidrosis. Tumors, radiation therapy, systemic sclerosis, burns, graft-versus-host disease, acrodermatitis chronica atrophicans, and Sjögren syndrome can distort the normal architecture of the skin with subsequent anhidrosis. Entities that lead to obstruction of the glands are also implicated in anhidrosis. Psoriasis, lamellar ichthyosis, miliaria, eczematous dermatoses, porokeratosis, and bullous diseases are examples of obstruction.

Evaluation

Detailed patient history is paramount in determining the possible underlying etiology. The next step would be to determine any potential contributing factors, such as medications. Colorimetric and or gravimetric testing can demonstrate diminished or absent sweating. Injection of local, intradermal cholinergic drugs to promote sweating can be utilized. However, this should only be done in a small area as the side effect profile and its associated risks preclude injection into large areas. If a patient is suspected of having peripheral neuropathy, testing the axon reflex sweating by injecting an intradermal picrate or nicotine sulfate at an appropriate dose may be performed. A skin biopsy from an affected area should always be obtained in patients with suspected anhidrosis to identify abnormalities of the sweat glands.

A quantitative sudomotor axon reflex test (QSART) assesses the autonomic nerves that mediate sweating. Mild electrical stimulation is applied to the skin via electrodes and acetylcholine enters the skin. Acetylcholine results in the stimulation of the sweat glands; and the sweat response is measured.

A silastic sweat imprint test also utilizes electrodes, however, pilocarpine is used to stimulate the sweat glands. indentations appear to mark the sweat droplets on a material formed of silicone rubber.

A thermoregulatory sweat test utilizes the body's core temperature to assess a correlation to sweat production. It assesses the thermo-regulatory sudomotor mechanism of the body.

Treatment / Management

Unfortunately, treatment options for anhidrosis can be limited unless an offending agent can be discontinued. Providers need to stress the importance of maintaining a cool environment for the patient. The use of water spray bottles for purposes of cooling can prove helpful. For those disorders due to clogged sweat glands, frequent and gentle exfoliation is useful. Those with disorders of cornification and overheating, such as lamellar ichthyosis, should be treated aggressively and monitored closely.

Although there is no remarkable evidence to support the use of corticosteroids, many case reports recommend the administration of corticosteroids in the early stages of AIGA. However, if the treatment is delayed or when the destruction of sweat glands has already occurred, then corticosteroids may not be beneficial.

The cornerstone for the treatment of anhidrosis is the management of the underlying cause, such as treating lung carcinoma if that is causing Horner syndrome and resulting in anhidrosis.

Differential Diagnosis

When considering anhidrosis, a differential diagnosis will depend on the underlying etiology.

Central and Neuropathic Anhidrosis

• Tumors, infarctions, or other alterations of the hypothalamus, pons, medulla, or spinal cord

• Horner syndrome

• Degenerative syndromes such as Ross syndrome or Shy-Drager syndrome

• Autoimmune autonomic neuropathy

• Congenital insensitivity to pain with anhidrosis

• Peripheral neuropathy due to diabetes mellitus, alcoholism, leprosy, amyloidosis

• Drugs

Drugs

• Nicotinic acetylcholine receptor antagonists such as hexamethonium and trimethaphan

• Muscarinic acetylcholine receptor antagonists such as atropine or scopolamine

• Calcium channel blockers

• Alpha-adrenergic blockers such as phentolamine

• Alpha2-adrenergic agonists such as clonidine

• 5-fluorouracil

• Topiramate

• Zonisamide

• Quinacrine

Peripheral Causes Due to Sweat Gland Abnormalities

• Genetic disorders such as ectodermal dysplasias, incontinentia pigmenti, Bazex-Dupré-Christol syndrome, Fabry disease

• Destruction from tumors, burns, radiation therapy, systemic sclerosis, morphea, Sjögren syndrome, graft-versus-host disease, acrodermatitis chronica atrophicans

• Obstruction from miliaria, ichthyoses, psoriasis, eczematous dermatoses, bullous diseases

Prognosis

The prognosis of anhidrosis varies depending on the type of anhidrosis. Anhidrosis associated with a genetic syndrome is generally lifelong. In the setting of drug-induced anhidrosis, it is usually reversible with the discontinuation of the medication. Anhydrosis secondary to a treatable cause is generally reversible and has a favorable prognosis.

Complications

Complications will depend on the underlying etiology. Heat-related illnesses are the most grave complications of anhidrosis. Children are more vulnerable because their core body temperature rises faster than adults and their heat loss mechanism is less efficient. Heat-related illnesses are:

• Heat cramps

• Heat exhaustion

• Heatstroke

The most feared complication, no matter the underlying etiology, is heatstroke.

Deterrence and Patient Education

Providers need to stress the importance of maintaining a cool environment for the patient. The use of water spray bottles for purposes of cooling can prove helpful. The patient is advised to wear loose and light clothing when it is warm and monitor their activity level not to overdo it. Frequent and gentle exfoliation is helpful for those disorders due to clogged sweat glands.

Enhancing Healthcare Team Outcomes

An interprofessional approach to anhidrosis is recommended. Anhidrosis and the underlying etiologies can cause severe emotional distress for patients. Quality of life may be low for patients of all ages secondary to societal scrutinization of their underlying condition (i.e., lamellar ichthyosis). Therefore, it is recommended to evaluate and arrange for mental health care in addition to the necessary medical care to address the underlying cause of the anhidrosis, if there is one. The outcome of patients with anhidrosis depends on the cause. There is no cure for those with inherited disorders, and it is a lifelong issue. The outcomes may improve for those with acquired anhidrosis by improving the primary condition or removing the offending medication. Most importantly, the patient should be actively involved in their care as the patient must maintain a cool environment and recognize the signs and symptoms of heat intolerance.

Introduction

Hyperhidrosis is a disorder of excessive sweating due to the overstimulation of cholinergic receptors on eccrine glands. This disorder is characterized by sweating beyond what the body uses for homeostatic temperature regulation. Eccrine glands are concentrated in areas such as the axillae, palms, soles, and face; therefore, these are the areas most commonly associated with hyperhidrosis. The acetylcholine negative feedback loop is likely impaired in these patients, which may help explain how a physiologic response can become pathologic. Studies have shown the prevalence of this disorder to be approximately 3% in the United States. Hyperhidrosis can result in emotional, psychological, social, and occupational impairment.

Hyperhidrosis is classified as primary and secondary, and the management and treatment can significantly differ for each. The primary disease typically presents earlier in life with more localized symptoms. The secondary disease typically presents due to adverse effects of medications or systemic disorders, particularly neurologic. The diagnosis most often is made clinically, and grading scales and tests are available to assist in determining the severity and localization. Laboratory workup may be indicated if a secondary cause is suspected to rule out infection, hyperthyroidism, diabetes mellitus, neurologic disorder, or a medication side-effect. There are several treatment options for hyperhidrosis, including topical aluminum chloride and oral anticholinergic medications, which are sufficient in patients with mild to moderate disease. Botulinum toxin A injections, sympathectomy, and local excision are also effective but reserved for patients that are resistant to conservative therapy.

Evaluation

It is important to first determine whether the source is primary or secondary, and a thorough history will help differentiate. If a secondary cause is suspected, providers should consider ordering a complete blood count, basic metabolic panel, thyroid-stimulating hormone, sedimentation rate, antinuclear antibody, hemoglobin A1C, and chest x-ray. These tests will assist in ruling out infection, kidney dysfunction, malignancy, diabetes mellitus, thyroid disease, an inflammatory disorder, or connective tissue disease, which can all be associated with hyperhidrosis. Providers can also thoroughly evaluate the severity of the disease by assessing the amount of palmar involvement using a measuring scale or determining the disease pattern using a starch-iodine test. These are not widely used because visual assessment alone is usually sufficient to make the diagnosis.

Treatment / Management

Treating hyperhidrosis has become easier for clinicians as more treatment options have become available, and a stepwise approach is often effective. There are many topical and systemic agents available to treat hyperhidrosis.

First-line therapy for hyperhidrosis includes over-the-counter aluminum chloride hexahydrate 20% for 3 to 4 nights, then nightly as needed. Skin irritation can occur, and patients often become intolerant of it in the long term.

Recently topical glycopyrronium tosylate (premoistened cloth containing 2.4% glycopyrronium solution) was approved to treat sweating.

Axillary sweating can be managed with aluminum chloride gel. While it does work, it is a potent irritant.

All topical agents can cause skin sensitization, and some, like tannic acid and potassium permanganate, can also cause skin discoloration. These agents appear to decrease sweating by denaturing keratin and thus occluding the pores of the sweat glands. The duration of the effect is very short.

If a patient does not respond to topical treatment or there are more generalized symptoms, oral anticholinergic medications, including oxybutynin 5 mg to 10 mg per day or topical glycopyrrolate 0.5% to 2.0%, should be considered. Anticholinergic agents can cause dry eyes, dry mouth, urinary retention, and constipation.

Iontophoresis two to three times weekly and botulinum toxin A injections every 3 to 4 weeks are effective if patients fail topical and oral drug therapy. Iontophoresis is a long-term treatment, and at best, its effects are mild. Many agents can be added to the water, but compliance with this treatment is low.

Botulinum toxin is effective; however, it is expensive, and repeat treatments are required. Some experts recommend botulinum toxin plus lidocaine for injection into the axilla. Botulinum toxin A acts by cleaving the SNAP-25 protein. This prevents the binding and presynaptic fusion of the acetylcholine vesicles with the nerve terminus and thus blocks the release of acetylcholine. It is the most appropriate treatment after failing topical antiperspirants and oral anticholinergics. Decreased perspiration can last from 6 to 24 months. Injections are usually performed in both axillae; however, they also can be useful in the palms and soles. These locations are less practical and will likely require local anesthesia to limit discomfort.

More invasive therapeutic measures are available, including sympathectomy or local excision as a last resort. Many surgical procedures have been developed to manage hyperhidrosis, including sympathectomy, radiofrequency ablation, subcutaneous liposuction, and surgical excision of affected areas. Of all these, sympathectomy appears to be the best treatment that is somewhat permanent. It involves excision of the ganglia (T2-T4) responsible for sweating. Resection of T1 ganglia is done for facial sweating, T2 and T3 for palmar sweating, and T4 for axillary sweating. The procedure can be done thoracoscopically, but complications are common. Compensatory sweating, gustatory sweating, Horner syndrome, pneumothorax, pain, and intercostal neuralgia have all been reported.

If a secondary cause is suspected, treatment of the underlying disorder or discontinuing the suspected medication is recommended in addition to regular therapy.

Differential Diagnosis

• Thyrotoxicosis

• Neuropathy

• Hypoglycemia

• Pheochromocytoma

• Menopause

• Lymphoma

• Tuberculosis

• Alcohol use disorder

Prognosis

The prognosis of hyperhidrosis is guarded. While not life-threatening, it can be cosmetically unacceptable and may even lead to difficulties with work. The quality of life for patients with severe hyperhidrosis is poor. No treatment works reliably, and the recurrence of hyperhidrosis is common with all currently available treatment options. Newer surgical treatments offer hope but do not always provide a cure.

Complications

• Social embarrassment

• Emotional distress

• Psychological distress

• Work or school-related disability

Pearls and Other Issues

Hyperhidrosis can affect not only a patient's physical health but also their psychological health. Patients, particularly those within the pediatric population, may suffer from social embarrassment leading to a lower quality of life than their peers. It is important for healthcare providers to screen for this condition.

Enhancing Healthcare Team Outcomes

Hyperhidrosis is a common complaint in clinical practice, and while there are many treatments available, many are unsatisfactory. Thus, the disorder is best managed by an interprofessional team that includes the primary care provider, nurse specialist, thoracic surgeon, plastic surgeon, and internist. The goal is to reduce sweating with minimal complications.

The pharmacist should educate the patient on all the topical and systemic products available to manage sweating. The patient should be aware of the adverse effects and potential complications.

A dermatologist should be consulted if the cause is unknown.

For recalcitrant cases, a thoracic surgeon should be consulted.

A mental health nurse and psychiatrist should assist with mental health support as the disorder can cause severe emotional distress.

Most topical and nonsurgical treatments do not work reliably. Surgery can be done, but recurrences are not uncommon. Patients need to be educated about all the potential treatments, including their effectiveness and any associated morbidity. A team approach can deliver the optimal treatment for hyperhidrosis and improve outcomes.

When the body becomes warm, sudoriferous glands produce sweat to cool the body. Sweat glands develop from epidermal projections into the dermis and are classified as merocrine glands; that is, the secretions are excreted by exocytosis through a duct without affecting the cells of the gland. There are two types of sweat glands, each secreting slightly different products.

An eccrine sweat gland is type of gland that produces a hypotonic sweat for thermoregulation. These glands are found all over the skin’s surface, but are especially abundant on the palms of the hand, the soles of the feet, and the forehead (image). They are coiled glands lying deep in the dermis, with the duct rising up to a pore on the skin surface, where the sweat is released. This type of sweat, released by exocytosis, is hypotonic and composed mostly of water, with some salt, antibodies, traces of metabolic waste, and dermicidin, an antimicrobial peptide. Eccrine glands are a primary component of thermoregulation in humans and thus help to maintain homeostasis.

An apocrine sweat gland is usually associated with hair follicles in densely hairy areas, such as armpits and genital regions. Apocrine sweat glands are larger than eccrine sweat glands and lie deeper in the dermis, sometimes even reaching the hypodermis, with the duct normally emptying into the hair follicle. In addition to water and salts, apocrine sweat includes organic compounds that make the sweat thicker and subject to bacterial decomposition and subsequent smell. The release of this sweat is under both nervous and hormonal control, and plays a role in the poorly understood human pheromone response. Most commercial antiperspirants use an aluminum-based compound as their primary active ingredient to stop sweat. When the antiperspirant enters the sweat gland duct, the aluminum-based compounds precipitate due to a change in pH and form a physical block in the duct, which prevents sweat from coming out of the pore.

Sweating regulates body temperature. The composition of the sweat determines whether body odor is a byproduct of sweating.

The integumentary system helps regulate body temperature through its tight association with the sympathetic nervous system, the division of the nervous system involved in our fight-or-flight responses. The sympathetic nervous system is continuously monitoring body temperature and initiating appropriate motor responses. Recall that sweat glands, accessory structures to the skin, secrete water, salt, and other substances to cool the body when it becomes warm. Even when the body does not appear to be noticeably sweating, approximately 500 mL of sweat (insensible perspiration) are secreted a day. If the body becomes excessively warm due to high temperatures, vigorous activity (image a,c), or a combination of the two, sweat glands will be stimulated by the sympathetic nervous system to produce large amounts of sweat, as much as 0.7 to 1.5 L per hour for an active person. When the sweat evaporates from the skin surface, the body is cooled as body heat is dissipated.

In addition to sweating, arterioles in the dermis dilate so that excess heat carried by the blood can dissipate through the skin and into the surrounding environment (image b). This accounts for the skin redness that many people experience when exercising.

When body temperatures drop, the arterioles constrict to minimize heat loss, particularly in the ends of the digits and tip of the nose. This reduced circulation can result in the skin taking on a whitish hue. Although the temperature of the skin drops as a result, passive heat loss is prevented, and internal organs and structures remain warm. If the temperature of the skin drops too much (such as environmental temperatures below freezing), the conservation of body core heat can result in the skin actually freezing, a condition called frostbite.

Integumentary System

All systems in the body accumulate subtle and some not-so-subtle changes as a person ages. Among these changes are reductions in cell division, metabolic activity, blood circulation, hormonal levels, and muscle strength. In the skin, these changes are reflected in decreased mitosis in the stratum basale, leading to a thinner epidermis. The dermis, which is responsible for the elasticity and resilience of the skin, exhibits a reduced ability to regenerate, which leads to slower wound healing. The hypodermis, with its fat stores, loses structure due to the reduction and redistribution of fat, which in turn contributes to the thinning and sagging of skin.

The accessory structures also have lowered activity, generating thinner hair and nails, and reduced amounts of sebum and sweat. A reduced sweating ability can cause some elderly to be intolerant to extreme heat. Other cells in the skin, such as melanocytes and dendritic cells, also become less active, leading to a paler skin tone and lowered immunity. Wrinkling of the skin occurs due to breakdown of its structure, which results from decreased collagen and elastin production in the dermis, weakening of muscles lying under the skin, and the inability of the skin to retain adequate moisture.

You might think that you are only supposed to sweat when you are hot, but once you hit puberty, you will also sweat when you are nervous. Your sweat glands, which are in places like your armpits, become more active during the teen years. That means you will sweat more, and your sweat will have a smell.

Don’t panic! Sweat and smell are normal parts of becoming an adult. Sweating also does an important job — it helps cool your body when you are hot.

You can follow some simple tips to keep from smelling bad:

• Shower or take a bath every day, making sure to wash your underarms, pubic area, and bottom.
• Use a deodorant, which helps get rid of smells, or an antiperspirant, which decreases sweating, or a product that has both of these in it.
• Talk to your doctor if these things do not work or you are worried about smelling bad.

Because underarm antiperspirants or deodorants are applied near the breast and contain potentially harmful ingredients, several scientists and others have suggested a possible connection between their use and breast cancer. However, no scientific evidence links the use of these products to the development of breast cancer.

Did anyone ever tell you that you smell bad? Funky breath or stinky underarms can happen to anyone, at any age. Whether or not you’ve noticed them, some body odors can signal a health problem. But most breath and body odors are normal.

“Bad breath is most often caused by bacteria on the teeth and tongue,” explains Dr. Madeleine S. Deming, an internal medicine expert at the NIH Clinical Center.

It’s normal if your breath smells a little in the morning, especially if you slept with your mouth open. A dry mouth allows bacteria to thrive. Bacteria that live in the mouth can make compounds that have sulfur. These compounds are especially stinky. They can smell like rotten eggs or onion, for example.

If bad breath isn’t cleared up by brushing your teeth or using mouthwash, it may be a sign of another issue. Over time, bacteria can cause tooth decay and gum disease. Decay and gum disease do not smell good. Both require a trip to the dentist for treatment.

Other causes of foul breath odor may be sinus, throat, or lung infections. These need to be treated by a health care professional, too.

Your breath can also carry clues of disease from other parts of your body. That’s because you exhale more than just air. Your breath also contains gassy compounds that move from your organs through the bloodstream into your lungs.

Breath that smells fruity or like rotten apples, for example, can be a sign of diabetes that’s not under control.

Rarely, people can have bad breath because of organ failure. A person with kidney failure may have breath that smells like ammonia or urine. Serious liver disease can make breath smell musty or like garlic and rotten eggs.

Compounds that are transported through the blood can also be released through your sweat glands. That can make your armpits and skin smell bad. It’s normal for stress to cause smelly compounds to be released through your sweat.

But your armpits can smell for other reasons too. Both moisture and hair enable bacteria to thrive. These bacteria can make smelly compounds. Bathing, shaving, and deodorant can help keep these odors in check.

Because certain diseases cause breath or body odors, NIH-supported researchers are developing an electronic “nose” to help doctors detect them. This research is at an early stage. In the lab, scientists can already analyze odor compounds from the body. They’ve even trained dogs to detect signs of certain cancers in breath samples.

If you’re concerned about a new or worsening body odor, “a trip to the doctor for evaluation is always the first step,” Deming advises. “Bad breath is best assessed by a dentist.”

Your dentist can examine your mouth for signs of trouble. If body odor is your concern, your doctor can conduct a physical exam. If needed, your doctor can suggest further tests.

“A trial of avoiding foods that are known to cause body odor may be considered. In rare cases of body odor due to an underlying medical condition, the treatment of that condition may help to manage the odor as well,” Deming says.

Concerned About a Body Odor?

To prevent strong breath or body odor:

• Bathe, wear clean clothes, and use deodorant.
• Clean and care for your teeth and mouth.
• Keep your mouth moist and your body dry.
• Avoid eating onions, garlic, and other strong-smelling foods.