The difficult to diagnose comorbidity that plagues Ehlers-Danlos syndrome patients

For many people with Ehlers-Danlos syndrome, unusually flexible joints are only the opening act. The far more disruptive part of the show may begin when standing up causes a racing heart, a shower feels like an endurance sport, and a quick trip to the grocery store requires the strategic planning normally reserved for a moon landing.

The often-missed comorbidity is dysautonomia, an umbrella term for disorders involving the autonomic nervous system. One of the best-known forms associated with hypermobile Ehlers-Danlos syndrome, or hEDS, is postural orthostatic tachycardia syndrome, commonly called POTS.

POTS can cause dizziness, palpitations, fatigue, weakness, nausea, headaches, temperature intolerance, exercise intolerance, and cognitive problems when a person is upright. Unfortunately, those symptoms can be divided among cardiology, neurology, gastroenterology, psychiatry, and several other specialties. Each clinician may see one piece of the puzzle while nobody notices the picture on the box.

This article explains how Ehlers-Danlos syndrome and dysautonomia can overlap, why POTS is frequently missed, what a responsible diagnostic evaluation involves, and how individualized treatment may improve daily function.

What is Ehlers-Danlos syndrome?

The Ehlers-Danlos syndromes are a group of inherited connective tissue disorders. Connective tissue helps provide structure and support throughout the skin, joints, blood vessels, organs, and other parts of the body. Common features across the EDS spectrum include joint hypermobility, tissue fragility, unusual scarring, and skin that may stretch more than expected.

However, EDS is not simply a condition that makes someone “double-jointed.” Depending on the type and the individual, it may also involve chronic musculoskeletal pain, repeated sprains, joint instability, dislocations or partial dislocations, headaches, fatigue, digestive symptoms, pelvic floor problems, and complications affecting multiple body systems.

Hypermobile Ehlers-Danlos syndrome is the most commonly encountered form. Unlike most other EDS types, hEDS currently has no laboratory or genetic test that can confirm the diagnosis. It is diagnosed clinically after a practitioner evaluates generalized joint hypermobility, systemic features, family and medical history, musculoskeletal complications, and alternative explanations for the symptoms.

That alone can begin a long diagnostic journey. Add dysautonomia, with its own collection of fluctuating and seemingly unrelated symptoms, and the medical mystery gains a second locked room.

Understanding dysautonomia and POTS

The autonomic nervous system manages processes that usually happen without conscious effort. It helps regulate heart rate, blood pressure, breathing patterns, digestion, sweating, temperature control, bladder function, and the narrowing and widening of blood vessels.

When this system does not regulate those functions appropriately, the result is called dysautonomia. POTS is one form of dysautonomia characterized by chronic symptoms of orthostatic intolerance and an excessive rise in heart rate after moving into an upright position.

What happens when a healthy person stands?

Gravity immediately pulls some blood toward the abdomen and legs. The body normally responds by tightening blood vessels, adjusting heart rate, and activating muscles that help return blood to the heart and brain. Most people never notice this quiet act of biological teamwork.

In POTS, that adjustment is less effective. The heart may speed up dramatically in an attempt to maintain circulation. The person can then experience lightheadedness, pounding in the chest, blurred vision, shakiness, weakness, or the feeling that thinking clearly has suddenly become an optional feature.

Despite the word “tachycardia,” POTS is not simply a fast heartbeat. It is a complex syndrome involving orthostatic intolerance and autonomic regulation. Some patients faint, but many do not. Feeling close to fainting, called presyncope, is more common and can still be profoundly disabling.

Common symptoms of dysautonomia in EDS patients

Symptoms vary widely and may change from one day to the next. Common complaints include:

• Dizziness or lightheadedness while standing
• A rapid or forceful heartbeat
• Near-fainting or fainting episodes
• Severe fatigue and exercise intolerance
• Brain fog, poor concentration, or slowed thinking
• Headaches or migraines
• Chest discomfort or shortness of breath
• Nausea, bloating, constipation, diarrhea, or abdominal pain
• Excessive sweating or reduced sweating
• Intolerance to heat or rapid temperature changes
• Trembling, internal shakiness, or a surge of adrenaline
• Purple or reddish discoloration of the feet and legs while standing
• Sleep disturbance and difficulty recovering after activity

Symptoms often become worse during hot weather, prolonged standing, dehydration, illness, menstruation, large meals, emotional stress, or physical overexertion. Hot showers are a notorious trigger because heat widens blood vessels while standing encourages blood to collect below the heart. For someone with POTS, that combination can turn ordinary shampooing into an extreme sport.

Why might Ehlers-Danlos syndrome and dysautonomia occur together?

Researchers have documented an association between hypermobility disorders, orthostatic intolerance, and POTS. However, the exact biological relationship remains under investigation, and no single mechanism explains every case.

More flexible blood vessels

One proposed explanation involves connective tissue in the walls of blood vessels. If veins are unusually compliant, they may not constrict as effectively when a person stands. More blood may then pool in the legs and abdomen, reducing the amount returning to the heart. A faster heart rate can become the body’s attempt to compensate.

Lower circulating blood volume

Some people with POTS appear to have a lower effective circulating blood volume. When less blood is available to return to the heart, remaining upright becomes harder. This may help explain why hydration and clinician-directed increases in sodium are useful for selected patients.

Small-fiber or autonomic nerve dysfunction

Small nerve fibers help regulate sweating, sensation, and blood vessel constriction. Dysfunction in these nerves may contribute to blood pooling, altered temperature regulation, pain, and other autonomic symptoms in a subset of patients.

Physical deconditioning

Joint pain, instability, fatigue, and repeated injuries may force an EDS patient to reduce physical activity. Extended inactivity can decrease cardiovascular conditioning and muscle-pump efficiency, which may intensify orthostatic symptoms. Deconditioning can worsen POTS, but it should not automatically be treated as the original cause. Telling a severely symptomatic patient to “just exercise more” without adapting movement to joint instability is not a treatment plan; it is a motivational poster wearing a lab coat.

Overlapping biological contributors

Autoimmune processes, abnormal stress-hormone responses, mast-cell mediator release, illness, surgery, trauma, and hormonal changes have also been investigated as possible contributors or triggers. Some people have hEDS, POTS, and symptoms suggestive of mast cell activation, but researchers continue to debate how consistently these conditions are biologically connected. Their coexistence should prompt careful evaluation rather than an automatic three-label package.

Why POTS is so difficult to diagnose

The symptoms cross medical specialties

A patient may tell a cardiologist about palpitations, a gastroenterologist about nausea, a neurologist about dizziness, and a primary care clinician about exhaustion. Standard tests may be normal within each specialty, especially when they are performed while the patient is sitting or lying down.

The body, inconveniently, does not organize itself according to hospital departments.

Symptoms may resemble anxiety

A racing heart, trembling, sweating, shortness of breath, and a surge of adrenaline can resemble a panic attack. Anxiety may coexist with POTS, just as it can coexist with any chronic illness, but it does not explain an objective and reproducible posture-related heart-rate response.

Psychological support can be valuable for coping with chronic symptoms. It should not replace an appropriate medical evaluation when symptoms consistently worsen upright and improve after lying down.

Symptoms fluctuate

A person may appear relatively well during a short office visit but be unable to prepare dinner later that evening. Hydration, recent meals, medication, sleep, temperature, hormonal changes, and time of day can influence testing. One normal set of vital signs does not necessarily capture a condition that varies with posture and circumstances.

Many clinicians receive limited training in autonomic disorders

POTS has become more widely recognized, partly because autonomic symptoms can develop after viral illnesses, including COVID-19. Even so, access to clinicians experienced in autonomic medicine remains uneven. Patients may visit numerous practitioners before someone records heart rate and blood pressure over several minutes of standing.

EDS may also be unrecognized

Some patients have never been evaluated for a connective tissue disorder. Their history of joint sprains, unusual flexibility, chronic pain, digestive problems, easy bruising, or poor recovery from injuries may have been treated as unrelated events. When neither hEDS nor dysautonomia has been recognized, the patient can accumulate symptoms and referrals without receiving a unifying assessment.

How POTS is diagnosed

POTS should be diagnosed by a qualified health professional using symptoms, medical history, physical examination, orthostatic measurements, and the exclusion of other causes.

Commonly used diagnostic criteria include:

• A sustained heart-rate increase of at least 30 beats per minute in adults within 10 minutes of standing or head-up tilt
• An increase of at least 40 beats per minute for adolescents ages 12 through 19
• Frequent symptoms of orthostatic intolerance that become worse upright and improve when the person lies down
• Symptoms lasting at least three months
• No significant sustained drop in blood pressure that would instead meet the definition of orthostatic hypotension
• No other condition that adequately explains the tachycardia

A smartwatch can help document patterns, but it cannot diagnose POTS. Consumer devices may be useful clues to bring to an appointment, not tiny wrist-mounted cardiologists.

The standing test and tilt-table test

During an active standing test, heart rate and blood pressure are measured after the patient rests horizontally and then at intervals after standing. A head-up tilt-table test produces a controlled change in posture while clinicians monitor the cardiovascular response.

Depending on the presentation, additional evaluation may include an electrocardiogram, laboratory testing, heart monitoring, an echocardiogram, autonomic reflex testing, sweat testing, or assessment for small-fiber neuropathy.

Conditions that must be considered

Clinicians should evaluate for other explanations such as dehydration, blood loss, anemia, fever, thyroid disease, medication effects, prolonged bed rest, an eating disorder, significant infection, inappropriate sinus tachycardia, or an abnormal heart rhythm. Symptoms should not be labeled POTS merely because the heart rate increases once after standing.

Treating dysautonomia in patients with EDS

There is no universal POTS treatment and no single medication works for everyone. Management is usually layered, individualized, and adjusted according to blood pressure, heart rate, associated conditions, mobility, and dominant symptoms.

Fluids and sodium

Many patients are advised to drink more fluid and increase sodium intake to support blood volume. The appropriate amount must be determined with a clinician, particularly for anyone with kidney disease, high blood pressure, heart disease, or another condition affected by fluid and sodium.

Compression garments

Waist-high compression garments or abdominal compression may limit blood pooling in the lower body. Knee-high socks alone may not provide enough support because a considerable amount of blood can collect in the abdomen and upper legs.

Physical rehabilitation

A carefully graded program may begin with recumbent cycling, rowing, swimming, or exercises performed while seated or lying down. Strengthening the legs and core can improve the muscle pump that helps move blood upward.

For an EDS patient, rehabilitation must also protect unstable joints. The goal is controlled strength and endurance, not stretching already-mobile joints into next Tuesday. A physical therapist familiar with both dysautonomia and hypermobility can help balance cardiovascular conditioning with joint protection.

Trigger management and pacing

Useful strategies may include rising slowly, avoiding prolonged standing, using a shower chair, cooling the environment, eating smaller meals, planning rest before symptoms become severe, and learning physical counter-maneuvers such as leg crossing or muscle tightening.

Pacing does not mean avoiding all activity. It means distributing activity so that one productive afternoon does not purchase three days of collapse at an outrageous interest rate.

Medications

When non-drug measures are insufficient, clinicians may prescribe medications intended to lower heart rate, increase blood volume, improve blood vessel constriction, or modify autonomic signaling. Examples sometimes used include beta-blockers, ivabradine, midodrine, fludrocortisone, and pyridostigmine.

Medication selection depends on the individual’s POTS pattern, blood pressure, other illnesses, and potential side effects. No medication should be started, stopped, or adjusted based solely on an online article.

Why coordinated care matters

EDS and dysautonomia frequently require cooperation among primary care, cardiology, neurology, physical therapy, pain management, gastroenterology, and other specialties. A central clinician who reviews the whole picture can reduce duplicated testing and prevent one treatment from making another problem worse.

For example, advice to exercise must account for unstable joints. Medication intended to reduce heart rate must account for low blood pressure. Dietary recommendations must consider gastrointestinal symptoms. Care works better when the patient is treated as one person rather than a traveling collection of body parts.

Experiences commonly reported by people living with EDS and dysautonomia

The following section reflects recurring themes described in patient surveys and clinical literature. It is a composite account rather than the medical story of one identifiable individual.

When ordinary activities become calculations

A typical morning may begin before the person leaves bed. They sit up slowly, wait for the room to stop drifting, drink water kept on the nightstand, and decide whether standing immediately is worth the gamble. The trip to the bathroom is only a few yards, but the body reacts as though it has been asked to sprint uphill carrying groceries.

Showering presents another calculation. Will the water be cool enough? Is a shower chair available? Is there enough energy left afterward to get dressed? Friends may see a familiar daily task. The patient sees heat, upright posture, slippery surfaces, unstable joints, and a heart rate that may launch into the stratosphere before the conditioner has been rinsed out.

The frustration of looking well

EDS and POTS are often invisible. A person may be smiling in a waiting room while using every available muscle to remain upright. When basic heart tests return normal, the relief of hearing that the heart is structurally healthy can be followed by frustration when the conversation ends there.

Some patients are told that they are stressed, out of shape, or paying too much attention to their pulse. They may begin doubting their own observations. Yet the same pattern returns repeatedly: symptoms increase while standing, in heat, after meals, or during illness and decrease when they lie down.

Being dismissed can eventually become part of the illness experience. Patients may prepare for appointments as though defending a legal case, carrying symptom logs, heart-rate records, medication lists, and carefully organized timelines. They are not necessarily obsessed with their health. They may simply have learned that an unorganized story is easier to disregard.

Work, school, and relationships

At work, prolonged standing may be impossible and prolonged sitting may still cause symptoms because the body remains upright. Brain fog can make familiar words disappear midway through a sentence. Meetings scheduled after a long commute may consume the energy needed to participate in them.

Students may miss early classes, struggle under fluorescent heat, or need to lie down between activities. Attendance records can make a fluctuating physical disorder look like poor motivation. Helpful accommodations may include flexible scheduling, access to water and salty snacks when medically appropriate, elevator use, rest breaks, temperature control, and permission to sit or recline.

Relationships can also be strained by unpredictable capacity. A person may accept an invitation on Wednesday and be physically unable to attend on Saturday. Repeated cancellations can look like disinterest unless friends and relatives understand that chronic illness does not consult the social calendar.

The relief and limits of diagnosis

Receiving a diagnosis can bring enormous relief. The symptoms finally have names, and the patient learns that the racing heart, nausea, weakness, and cognitive fog are not character flaws. However, diagnosis is not a magic switch. Treatment often involves experimentation, gradual rehabilitation, trigger management, and repeated adjustment.

Progress may be measured in practical victories: taking a shower without needing an hour to recover, preparing a meal while seated, walking through a store, returning to part-time work, or attending a family event with a planned rest period.

The most helpful healthcare encounters often begin with belief. A clinician does not have to possess every answer on the first visit. Listening carefully, measuring orthostatic vital signs correctly, acknowledging uncertainty, and coordinating appropriate referrals can transform the patient’s experience from an argument into a partnership.

When symptoms require urgent medical attention

Not every episode of chest pain, fainting, or rapid heartbeat should be assumed to be POTS. Emergency evaluation may be necessary for new or severe chest pain, major breathing difficulty, a sustained irregular heartbeat, fainting during exertion, significant bleeding, stroke-like symptoms, a serious injury after fainting, or symptoms that are substantially different from the person’s usual pattern.

People with EDS may also have risks that vary by subtype. New severe symptoms should therefore be evaluated on their own merits rather than automatically attributed to an existing diagnosis.

Conclusion

Dysautonomia, especially POTS, can be one of the most disabling and easily overlooked problems affecting people with hypermobile Ehlers-Danlos syndrome. Its symptoms cross body systems, fluctuate with posture and environment, and can resemble more familiar conditions. That combination creates fertile ground for fragmented care and delayed diagnosis.

Recognition begins with asking the right questions. Do symptoms worsen while upright? Does the heart rate rise excessively after standing? Is there a history of joint hypermobility, instability, pain, or tissue fragility? Have dehydration, anemia, thyroid disease, medication effects, and abnormal heart rhythms been considered?

An accurate diagnosis does not solve every problem, but it replaces confusion with a direction. With individualized hydration and sodium guidance, compression, joint-safe rehabilitation, trigger management, medication when appropriate, and coordinated care, many patients can improve function and reclaim parts of daily life that once seemed out of reach.