Coexisting Conditions

Coexisting conditions are two or more medical conditions occurring at the same time. The conditions may be linked or independent from one another.

Common coexisting conditions of dysautonomia include, but are not limited to:

Ehlers-Danlos Syndromes 1 2 3, Mast Cell Activation Syndrome 4 5 6, Gastroparesis 7,
Intestinal Dysmotility 8 9 10 11, and Chiari Malformation 12 13.

Other coexisting conditions include: migraines, autoimmune disorders 14 15, fibromyalgia 16 17,
Parkinson’s disease 18 19, diabetes, and long COVID 20 21.

There are many theories about possible mechanisms linking dysautonomia with certain coexisting conditions 22 23. Further research is needed to better explain the prevalence of coexisting conditions in patients with dysautonomia.

Ehlers-Danlos Syndromes (EDS)

Ehlers-Danlos Syndromes (EDS) are a group of hereditary disorders affecting the integrity of connective tissue throughout the body, specifically the skin, joints, and blood vessels. Currently, thirteen subtypes of EDS have been identified, with the hypermobile type being the most common ²⁴.

Symptoms

The physical signs and symptoms of EDS vary across subtypes, however all present with the clinical features of joint hypermobility, skin extensibility, and tissue fragility ²⁵. For more information on each subtype’s symptoms, visit The Ehlers Danlos Society

Diagnosis

A diagnosis of EDS is made through a comprehensive history and physical exam, with particular focus on clinical evidence of connective tissue abnormalities. For patients with suspected hypermobile EDS, the diagnosis is based on a set of clinical criteria that any physician can perform. However, for those who suspect they have other forms of EDS, they may require a referral to a geneticist for further testing. A geneticist can confirm the diagnosis for all subtypes except hypermobile EDS, for which a genetic variant has not yet been identified ²⁶.

Clinical suspicion of hypermobility can also be supported through the use of the Beighton scale, a 9-point scoring system utilized by medical professionals that assesses for joint laxity and hypermobility ²⁷. When patients present with signs of joint hypermobility but do not meet the diagnostic criteria for EDS, hypermobility spectrum disorder (HSD) should be considered. For more information on EDS and how it is diagnosed visit The Ehlers-Danlos Society.

Treatment

Currently, there is no medical treatment directly targeting the collagen production in EDS. Treatment and therapy are aimed at minimizing injury through physical therapy, occupational therapy, supportive bracing to help stabilize joints, and symptom management ²⁸.

Dysautonomia Connection

Patients with EDS commonly present with symptoms of dysautonomia, specifically orthostatic intolerance. Research has demonstrated a link between connective tissue laxity and the cardiovascular and autonomic dysfunction present in dysautonomia ²⁹ ³⁰. More information is needed to understand the exact connection between the two. Research is ongoing.

EDS Additional Resources

The Ehlers Danlos Society: Home | The Ehlers Danlos Society : The Ehlers Danlos Society (ehlers-danlos.com)

NIH information on Ehlers Danlos Syndrome: Ehlers-Danlos syndromes | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program (nih.gov)

American Journal Of Medical Genetics Part C: Seminars In Medical Genetics Supplement To The American Journal Of Genetics

Mast Cell Activation Syndrome (MCAS)

Mast Cell Activation Syndrome (MCAS) is a condition in which the mast cells inappropriately degranulate, or release their chemical mediators, in response to changes in the external and internal environment (often termed as “triggers”) ³¹. Mast cells, a type of white blood cell, are found in connective tissue, with highest concentrations found in the skin, digestive tract and lungs. Mast cells have long been recognized as a key player in allergic diseases and reactions. When exposed to an allergen, mast cells release a variety of inflammatory chemicals. The most well known of these chemicals is histamine which causes the classical symptoms of allergies, including nasal congestion, itching of the skin ³². Histamine release also causes increased stomach acid secretion, lower leg swelling, and drops in blood pressure ³³.

Triggers

Triggers for MCAS are diverse and unique to each patient, but commonly include natural and chemical odors, perfumes, foods, extremes of temperatures, stress, and exercise ³⁴. Individuals with MCAS may also react to common medications such as NSAIDs, antibiotics, and opioids. Patients should identify and record their full range of unique triggers with the understanding that their triggers may change over time ³⁵.

Symptoms

MCAS is termed a multisystem disorder due to its ability to affect nearly every organ system throughout the body ³⁶. MCAS can present with allergic symptoms, including hives, rashes, welts when the skin is scratched (dermatographism), diarrhea, and anaphylaxis. Additional symptoms of inflammation can include bone pain, fatigue, headaches, and body aches ³⁷.

Diagnosis

Diagnosing MCAS involves three separate criteria ³⁸ . The first criterion is the presence of chronic symptoms related to MCAS involving two or more organ systems. The second criterion is the laboratory evidence of MCAS, and the third is the improvement of symptoms with the use of MCAS therapies. Common laboratory testing for MCAS involves the detection of the mediators released when mast cells degranulate and include blood histamine or tryptase levels and 24-hour urine histamine and prostaglandin levels ³⁹ ⁴⁰. However, it is important to note that there is disagreement among MCAS researchers regarding diagnostic criteria ⁴¹.

Treatment

Treatment for MCAS begins with the patient identifying and avoiding triggers ⁴². Medications commonly used as part of treatment may include those that prevent the degranulation of mast cells, called mast cell stabilizers, as well as antihistamines and leukotriene inhibitors ⁴³. Aspirin, corticosteroids, and Omalizumab (a monoclonal antibody that blocks the binding of IgE to receptors) may also be used as part of a treatment plan ⁴⁴. Medical therapy is individualized and often can involve trials of different medications to find what works best for the individual.

Dysautonomia Connection

MCAS is a known coexisting condition of one type of dysautonomia, Postural Orthostatic Tachycardia Syndrome (POTS) ⁴⁵. There is also a significant overlap in symptoms between MCAS and POTS, such as hypotension and flushing ⁴⁶. Although the direct connection between MCAS and POTS is unclear, some interactions between mast cells and the nervous system are known. Mast cells are located in proximity to nerve endings and can have direct effects on the nervous system through release of their mediators. Likewise, nerve stimulation can lead to mast cell activation . While clinical observations indicate treatment of MCAS may alleviate some symptoms of POTS, research is needed to understand the connection between these two syndromes ⁴⁷.

MCAS Additional Resources

Mast Cell Action: https://www.mastcellaction.org

The American Academy of Allergy Asthma & Immunology: https://www.aaaai.org/conditions-and-treatments/related-conditions/mcas

The Mast Cell Disease Society: https://tmsforacure.org

Gastroparesis (GP)

Gastroparesis (GP), or delayed gastric emptying, is a digestive disorder that affects the stomach’s ability to move food along the gastrointestinal tract ⁴⁸. There are several potential causes of gastroparesis including diabetes ⁴⁹. Forms of dysautonomia are associated with gastroparesis ⁵⁰ potentially due to autonomic neuropathy ⁵¹.

Symptoms

GP symptoms include: nausea, feeling full early (early satiety), weight loss/malnutrition, vomiting, abdominal pain, and bloating ⁵².

Diagnosis

The diagnosis of GP can involve a physical exam, examining medical history and symptoms, and a gastric emptying test ⁵³. Clinical symptoms are an important part of the diagnostic process. This is because tests for gastric emptying can be unreliable ⁵⁴. Gastric emptying varies significantly by the day, which can lead to unreliable results ⁵⁵.

Gastric emptying test assesses the speed at which the stomach empties food. A gastric emptying test may be performed through an emptying scan (scintigraphy) or through the use of a SmartPill that records its trip through the GI tract ⁵⁶. During the commonly-used scintigraphy, the patient eats a meal that contains a medically-safe radioactive material, allowing the food to be visualized on a scanner ⁵⁷. Images of the abdomen are taken periodically over the course of the test. Typically, a diagnosis is made when 10% or more of the meal still remains in the stomach after four hours ⁵⁸. Other tests that may be involved in diagnosing GP or ruling out any other causes can include blood tests and an upper GI endoscopy ⁵⁹.

Treatment

Dietary recommendations are often the first-line treatment for GP and can include eating small meals more frequently throughout the day. To meet nutritional needs and minimize symptoms, it is also recommended that patients eat foods lower in fiber and fat, as well as foods softer in consistency ⁶⁰ ⁶¹. If dietary modifications are not sufficient in helping manage symptoms, medications that increase the stomach’s ability to empty are often used. Medications for GP are symptom and cause specific and may vary between people. Medications may assist with gastric emptying or symptoms related to nausea and vomiting ⁶². In some cases, alternative forms of nutrition may be necessary, including a feeding tube, either into the stomach or small intestine, or total parenteral nutrition (TPN), a form of IV nutrition ⁶³.

Dysautonomia Connection

Gastrointestinal symptoms, including those associated with GP, have been reported as some of the most common complaints in patients with postural orthostatic tachycardia syndrome (POTS) ⁶⁴. In a study of 4,835 individuals with POTS, 14% of patients reported being diagnosed with GP and over 70% of patients complained of various gastrointestinal symptoms ⁶⁵. The autonomic nervous system, the part of the nervous system that is malfunctioning in patients with dysautonomia, is responsible for controlling the digestive process ⁶⁶. While a dysregulated nervous system may cause gastrointestinal symptoms, there may be other mechanisms causing gastrointestinal dysfunction such as abnormalities with the GI connective tissue or gut hormonal secretions ⁶⁷ ⁶⁸. Regardless of the underlying cause, dysfunction of the gastrointestinal system can lead to severe problems in dysautonomia patients such as weight loss and malnutrition. Also, in patients with some types of dysautonomia, blood retention in the gut during digestion can exacerbate presyncopal symptoms. There are currently no unique treatments for patients with both gastroparesis and POTS; treatment of each individual condition can provide some degree of overall symptom relief ⁶⁹.

Gastroparesis Additional Resources

G-PACT, gastroparesis patient association for cures and treatment: Home - G-PACT (g-pact.org)

International Foundation for Gastrointestinal Disorders:About Gastroparesis

The Oley Foundation for resources on enteral nutrition and parenteral nutrition: Oley Foundation

Chiari Malformation (CM)

Chiari malformation (CM) is a condition in which the cerebellum, the lowest part of the brain responsible for balance and coordinating movement, extends into the spinal canal. CM can be either congenital or acquired. Congenital Chiari malformation is the result of fetal abnormalities of the skull and spinal cord, the causes of which are being investigated. Acquired Chiari malformation occurs with excessive drainage of spinal fluid from the lumbar or thoracic areas of the spine due to traumatic injury to the spine or other diseases including spinal infection ⁷⁰.

Symptoms

The most common symptom of CM is headache and neck pain, particularly during coughing, sneezing, or straining. These are known as “tussive headaches”. Other specific cranial symptoms include vision disturbance, impaired hearing, and swallowing problems ⁷¹. More generalized symptoms include balance problems, dizziness, and muscle weakness ⁷². Symptoms are assumed to be related to the impaired regulation and circulation of cerebrospinal fluid at the base of the skull.

Diagnosis

Many diagnostic tests are useful for identifying CM, including MRI or CT scan. The MRI and CT scan are helpful to assess the anatomy of the Chiari malformation and the degree of the obstruction of the cerebrospinal fluid spaces at the base of the skull as well as to detect associated abnormalities of the base of the skull or the cervical spine including instabilities ⁷³.

Treatment

Treatment for CM depends on the degree of symptoms the patient experiences. Asymptomatic patients can be observed by their physicians with MRI monitoring. For symptomatic patients, medications can be prescribed for pain and headaches, and surgery may be recommended to correct the malformation in patients whose pain and symptoms are not managed by medications or physical measures ⁷⁴.

Dysautonomia Connection

Regulation of the autonomic nervous system is also impaired in patients with CM due to pressure on the brainstem from cerebellar compression or instabilities at the base of the skull causing brainstem irritation. This irritates the autonomic nervous system controlled by the lower brainstem affecting the proper functions of the autonomic nervous system ⁷⁵. Therefore, treatment of CM may also relieve a patient’s symptoms of dysautonomia ⁷⁶.

Chiari Malformation Additional Resources

Bobby Jones Chiari & Syringomyelia Foundation

NIH information on Chiari Malformation: Chiari malformation type 1 | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program (nih.gov)

Video- Understanding Chiari Malformation: Understanding Chiari malformation - YouTube

American Syringomyelia and Chiari Malformation Alliance Project: Syringomyelia and Chiari Malformation - ASAP » American Syringomyelia & Chiari Alliance Project

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