Inflammatory POTS

Mast Cell Activation Syndrome (MCAS)

One form of systemic inflammation that can result in POTS is Mast Cell Activation Syndrome (MCAS). Patients with MCAS can suffer from itching, flushing, hives, difficulty breathing, gut pain and digestive issues, burst of anxiety, tachycardia, and can experience difficulty with temperature control (often alternating between feeling very hot, with tachycardia and flushing, to becoming acutely cold, often shivering with the inability to raise their body temperature). Antihistamines can be helpful, but a positive response to antihistamines does not mean the patient must have MCAS.

A patient may have every symptom of Mast Cell Activation Syndrome (MCAS), for example, but if the diagnosis is made only on symptomatic presentation (and in the face of negative bloodwork) additional forms of inflammation may be of primary concern.  If treated as MCAS when testing for MCAS is negative, the patient can improve but will often be left to suffer. Even worse, the patient may assume that everything has been done to help them and they must learn to accept their condition. This misdiagnosis can lead to unnecessary suffering, but digging deeper into the source of the inflammation and treating can often improve the patient’s condition.

At POTS Care, we see many patients misdiagnosed as having MCAS because they present with the symptoms of MCAS, yet no one has explored their case deeply to locate inflammation that can mimic MCAS.

Eosinophils are typically considered to be “allergy cells”. They become activated in allergic exposure and release numerous chemicals into the body, including histamine. Eosinophils are activated in “atopy” which is characterized by a tendency to be “hyperallergic”. Often, patients present with eczema (atopic dermatitis), allergic asthma, and allergic rhinitis (hay fever) and often all three of these!

Fairly recently, however, focus on eosinophils has turned to those patients with eosinophilic activation without true allergy! It is critical to differentiate allergy eosinophilic activation from non-allergic in order to treat the patient correctly. Even more confusing, some patients can exhibit both!

Eosinophilic problems are especially predominant in the gut and throat (eosinophilic esophagitis and eosinophilic gastroenteritis) yet can be missed with biopsies. Importantly, this inflammatory condition can mimic Mast Cell Activation Syndrome (MCAS) and we must evaluate patients carefully to diagnose this (and other MCAS mimickers correctly).

Long-Haulers Coronavirus Infection

Viral infections are a common trigger for Inflammatory POTS and COVID/SARS and other coronaviruses are no exception. Rather than addressing this post-viral condition as an infection, a close evaluation of an abnormal inflammatory response and autoinflammatory conditions offers treatment options. Some bacterial infections (usually gram-negative bacteria with LPS coatings) can also cause this abnormal inflammatory response.

Adrenal Disorders

The adrenal glands, located at the tops of the kidneys, receive signals from the pituitary gland in the brain. The adrenal glands help the body control inflammation by releasing cortisol. When exposed to injury or stress (physical or mental), the production of cortisol helps to reduce the inflammation and allow recovery. When the pituitary gland or adrenal glands are not working properly for any reason, the production of cortisol is often insufficient to help control inflammation. The patient can have a very poor stress response, and levels of cortisol can become so low that nausea, weakness, and the inability to stay awake can occur. Yet when treated, patients can rather immediately improve.

Addison’s Disease, Secondary Addison’s Disease, Autoimmunity, and Congenital Adrenal Hyperplasia are a few conditions that must not be overlooked as contributors to chronic inflammation and autoinflammation.

Addison’s Disease

Addison’s disease can be both primary (due to adrenal disease) and secondary (due to something affecting the adrenal gland). These conditions present somewhat differently, and symptoms can wax and wane — often making diagnosis elusive.

Congenital Adrenal Hyperplasia

Congenital Adrenal Hyperplasia (CAH) may be “Classic” or (much more commonly) “Nonclassic”. Nonclassic CAH is not uncommon, with some research indicating an incidence as high as one in one hundred people. Yet patients can present as basically normal and functional until hit with high levels of stress or injury. Blood work is usually able to identify this condition but may involve stimulation tests (usually performed and interpreted by endocrinologists). There are many possible genes involved in CAH, but one overlap we are certain to rule out involves hypermobility (or “EDS — Ehlers-Danlos syndrome) and CAH. This genetic combination involves Tenascin X (part of connective tissue) and a CYP21A2 gene (controlling 21-hydroxylase which can cause CAH). If also involving a complement protein (C4) the triad is often referred to as “RCCX”.

We see congenital adrenal hyperplasia in less than 10% of patients at POTS Care, but we see just as many people with genetic overlap conditions that mimic RCCX or CAH and are careful to evaluate everyone as an individual.

Autoimmune Conditions

Autoimmunity (conditions where the body begins to attack itself) may include Systemic Lupus Erythematosus (“Lupus”), Hashimoto’s Thyroiditis, Hughes Syndrome (Antiphospholipid Syndrome), Rheumatoid Arthritis, Ankylosing Spondylitis, and numerous additional conditions.

At POTS Care, we have found that autoimmunity, although not uncommon in POTS patients, is generally a secondary issue. Identification of the autoimmune condition opens up additional treatment options, but search for the underlying conditions must not stop there. Some autoimmune conditions (such as Sjogren’s Syndrome, for example) can cause POTS or POTS-like episodes. We never assume that the autoimmune condition is the only reason for the symptoms, however. Digging deeper, we can often find undiagnosed contributors that when treated, can allow dramatic patient improvements.

Endometriosis

Endometriosis is associated with an inflammatory response that can contribute to both POTS (autoinflammation) and chronic pain.

Genetic Disorders Affecting Inflammation

The inflammatory cascade is quite complex. Any stimulus for inflammation calls into play many inflammatory cells, which then release chemicals (such as inflammatory cytokines and chemokines) that then call in additional inflammatory cells.

The chemicals that these cells release can help us fight infection and begin injury repair but when chronic, these chemicals can then damage healthy tissue. This damage (often accompanied by pain) can present similarly to autoimmune conditions — but with different genetics at play — and different treatment options for the patient.

At POTS Care, we are devoted to locating and identifying these genetic inflammatory conditions whenever possible.

References

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Kohno R, Cannom DS, Olshansky B, et al. Mast Cell Activation Disorder and Postural Orthostatic Tachycardia Syndrome: A Clinical Association. J Am Heart Assoc. 2021;10(17):e021002. doi:10.1161/JAHA.121.021002

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