Pseudoxanthoma Elasticum

My father had a twin brother who began losing his eyesight while in his fifties. At first, his doctors thought the loss-of-eyesight was due to Macular Degeneration, which is common as people age. However, one astute doctor realized it was something different. My uncle was diagnosed with a condition cited as:

Pseudoxanthoma Elasticum (PXE)

I am writing about it here on the Steem blockchain in hopes that it might help others that are having similar problems, to document some of the issues with which my family has dealt, and to provide resources as well as education in general.

Pseudoxanthoma Elasticum (pronounced: [soo″dō-zan-thō´mah e-las´tĭ-kŭm]) is a mouthful, which is why the abbreviation "PXE" is so helpful. Along with that big name comes a big disorder, which is systemic, meaning: "pertaining to or affecting the body as a whole" ^[1] as opposed to affecting only one part of the body.

The professional version of the Merck Manuals gives a nutshell definition:

Pseudoxanthoma elasticum is a rare genetic disorder characterized by calcification of the elastic fibers of the skin, retina, and cardiovascular system. [source]

PXE affects more than the skin, retina, and cardiovascular system, though. As with any disease or disorder, different people can be affected in different ways, with various symptoms presenting first in some patients and other symptoms presenting first in other patients, and all those symptoms progressing at varying rates. With PXE, some patients report changes in skin first, and other patients report changes in eyesight first.

It's in the genes...

Pseudoxanthoma Elasticum is a genetic disorder, meaning that it is passed via genes through familial lineages. For anyone with a detailed interest in genetics, PXE results from "mutations in the ABCC6 gene on the short arm of chromosome 16." ^[9]

[PXE] is due to mutations in the ABCC6 gene on chromosome 16p13.1. Over 100 mutations in the gene have been described. The type and number of mutations influence the age of onset and severity of the disease ^[3]

Different sources cite different probabilities for someone's being affected by the disorder. One such source suggests:

The reported prevalence of Pseudoxanthoma Elasticum is about 1:25,000. Females are twice as likely to be affected as males. The disease occurs in all ethnicities ^[11]

Besides my father and his twin brother, other ancestors in my family had PXE, too. One of my father's great aunts had it, as well as his maternal grandmother — in fact, she was going blind and died from complete kidney failure due to PXE shortly after her 27^th birthday in 1902.

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░░░░   First symptoms are only the tip of the iceberg   ░░░░

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Blindness...

Since the eyes are affected in the early stages of symptoms, an exam by a trained ophthalmologist (a doctor who specializes in diseases and disorders of the eyes) is often the first confirmation of the disorder. My uncle's diagnosis was detected by an opthalmic exam, and then confirmed by the ophthalmologist's examining my uncle's neck. Since the disorder is inherited, my father was urged to be tested as well, and he tested positive. It wasn't long before he began losing his eyesight, too.

When an ophthalmologist examines the eyes, blood vessels and other features can be seen. Among those features are sometimes abnormalities which can indicate diseases and disorders of the eyes as well as systemic diseases and disorders that manifest first in the eyes, such as PXE, diabetes, and others.

One of those abnormalities might be angioid streaks (pronounced like the woman's name "Angie" with "–oid" as in "Android" on the end). Angioid streaks are formed when one of the layers of the choroid (a vascular layer adjacent to the retina) called Bruch's Membrane becomes hard and cracks through the process of calcification — a similar process to that by which the living tissue of a tree can become "petrified." The presence of these angioid streaks often serves as a precursor to deeper-rooted health issues that can soon manifest, such as PXE, Paget's Disease, Sickle Cell Disease, or others.

^{Angioid Streaks, indicated by arrowheads, source: New England Journal of Medicine}

The loss of eyesight due to PXE is not the same as Macular Degeneration, but the effect on the vision appears similar from the viewpoint of the patient. The central portion of one's vision becomes distorted and it becomes difficult to read fine print and discern details. A blackish spot begins to appear in the center of one's field of vision, which slowly increases in size over months and years until almost all of the visual field is obscured.

^{Progressive Macular Degeneration, source: Eyes of York Cataract & Laser Center}

Although my father's twin brother began losing his eyesight first, the decline in his vision progressed slowly, over the course of years. My father's vision deteriorated at a much faster rate, however. In the last few years of my father's life, his vision was only about 1%–2%. He could see nothing in his central vision, could not read, could not identify faces, and could only see fleeting, vague shapes and colors around the very edge of his visual field, and only then in brightly-lit conditions. In dimly-lit conditions, he was essentially in total blindness. He carried a white cane and used it keep from tripping over curbs and such, plus it served as a signal to others that he was legally blind.

PXE is a rare condition, so the odds of anyone reading this and having the condition is fairly small. However, If anyone wants to be tested by an ophthalmologist, indicate that you wish to be examined for PXE and mention that "Cougan's Dystrophy with angioid streaks" is often an ophthalmic diagnosis for which the doctor should examine. My brother and I were both examined and no indication was found for it — thus far — but it could surface at any time. Because of the familial history and the genetic vector, periodic testing is advisable.

^{PXE manifestation on skin of one patient, © Springer Science+Business Media}

Skin Conditions...

Among the first manifestations of PXE in some patients is changes in the skin. The skin on the back or sides of the neck is often first affected, and takes on a tough, leathery appearance, sometimes with yellowish splotches. In fact, the name for this disorder derives from the word Xanthoma, which comes from the Greek ξανθός (xanthós), meaning "yellow." A true xanthoma, in medical terms, is a deposit of lipids (fats) within the skin itself.

PXE is different, though, because it causes an actual change to the skin through calcification of the elastic fibers. However, it looks a bit like a xanthoma, so thus: psuedo٠xanthoma, of the elastic fibers (elasticum).

For people who frequently spend time outdoors (as was the case with my father and his twin brother, who worked hard all their lives), the presence of xanthomas or pseudoxanthomas of the skin could be confused with the effects of the elements, which can make detection problematic. This provides a possible explanation as to why some patients report problems with the eyes first, rather than the skin, even though the skin appears to be affected first in the majority of cases.

Gastrointestinal Bleeding...

Bleeding in the gastrointestinal tract is experienced by some patients. My father had a history of "bleeding ulcers" in his stomach for a number of years, and they might have been a result of the PXE as well. He preferred a bland diet, anyway, and the addition of Omeprazole® to his daily regimen of medication seemed to help, and helped with his Acid Reflux problem somewhat, too. He still experienced uncomfortable feelings in his abdomen from time-to-time, but the bleeding ulcers finally were controlled.

Cardiac Issues...

Not long after my uncle began losing his eyesight, he suffered cardiac issues, as is common with PXE patients, and eventually had to have surgeries where six coronary bypasses were performed. Fortunately, my father did not suffer cardiac issues until much later. As stated earlier, PXE, like other diseases and disorders, can affect people at different rates and in different ways.

My father only experienced cardiac issues later in life, which manifested in ways such as Aortic Stenosis (narrowinig of the aortic valve exiting the heart), Atrioventricular Block (AV block, electrical signal disruption between the atria and ventricles within the heart), and an episode of ST Depression (an irregularity in the heartbeat) in his EKG which delayed a hip-repair surgery. Those issues may, or may not, have had anything to do with the PXE.

Circulatory Issues...

Issues with the circulatory system, in general, might be present, too, by compromising the elasticity of blood vessels. My father and his twin brother, both, had a condition which they referred to as "hardening of the arteries."  There are several medical terms for such, depending on which vessels are affected and whether plaque is present or not. The word arteriosclerosis is the more encompassing term. This condition affects many people as they age, whether they have PXE or not, but the presence of PXE genetics seems to make the condition worse.

My father and his twin brother both had diminished circulation in their lower-legs and feet because of the arteriosclerosis. This led to their lower extremities being cold much of the time, and the diminished blood flow often led to their having a "wobbly feeling" in their legs when standing or walking. This only served to make them more of a fall-risk than the blindness alone. My uncle's arteriosclerosis was worse than Dad's, and my uncle even had stents inserted into the arteries in his legs once, just to help keep them open.

Arteriosclerosis can also be a partial cause of the phenomenon of elderly people's falling and not being able to get up again by themselves. There were many times over the years that my father fell, could not get up on his own, and was totally unable to assist me in getting him up off the floor. At those times, I had to struggle to lift his weight all by myself.

Diminished Kidney Function and Failure...

Both my father and his twin brother experienced diminished kidney function, which was found during routine blood tests when serum creatinine and BUN (Blood Urea Nitrogen) levels were examined, both of which serve as indicators of kidney ("renal") function. For someone with PXE (or other diseases and disorders which affect the kidneys), such tests should be performed on a regular basis.

Renal dysfunction can be a serious medical condition. Potentially harmful waste products, when not be removed from the blood steam, can begin to affect other parts of the body. Also, improper renal function can cause some beneficial things to be removed from the body.

Renal dysfunction can also lead to other conditions. For instance, we were advised by the local hospital that renal failure can cause the body to be deficient in Calcium, leading to weak bones. This is a common occurrence in PXE patients. Here is the reason that happens:

Specialized cells in the kidneys produce the hormone calcitriol, a form of vitamin D, when calcium levels in the blood are too low. This hormone increases the body’s uptake of calcium from food and the release of calcium from the bones. [source]

Yet, if the kidneys are not functioning properly, or are completely shut down, the calcitriol hormone isn't produced (or is in too-low amounts) and calcium deficiency results.

Kidney dysfunction can also cause an imbalance of many electrolytes in the body, which includes sodium, potassium, magnesium, chloride, calcium, and others. Because of PXE's effects on the kidneys, my father's electrolytes frequently became imbalanced despite my best efforts to keep him hydrated, eating a healthy, balanced diet, and taking the proper supplements.

Dehydration and electrolyte imbalance can cause many problems of their own. Especially in the elderly, dehydration can affect mental acuity. Often, the first sign of my father's entering a dehydrated state was mental confusion. Such typically manifested with small things: e.g., thinking we hadn't had lunch yet, when we'd just eaten an hour ago, and arguing that we had not had lunch when I told him that, yes, we had. Probably the most heartbreaking incident occurred several months after my mother died and my father was convinced she was simply asleep in the bed; I actually had to take him back to their bedroom and pull-back the covers so he could feel (because he could not see) that she was not there. It was later that day, when other similar things kept happening that I realized he was dehydrated. Many times over the years, I had to take him to the ER at the local hospital to get an IV of fluids, and then he was back to his old self again afterwards. Sometimes, he had no memory of having acted strangely, but usually the past few hours seemed like a hazy "fog" in his memory, with no details clear to him.

Fortunately, my father never endured complete kidney failure, but his twin brother did. During the final few months of his life, my uncle's kidneys completely stopped working and he was hospitalized in the ICU. Doctors ordered dialysis, hoping that it would "kick start" his kidneys into functioning again. After two or three sesssions of dialysis, his kidneys did, indeed, start working again, but what a scare it was for the whole family.

Osteoporosis...

My father's blindness, plus his general unsteadiness brought on by age and arteriosclerosis, caused him to fall sometimes. Almost every fall resulted in a either a small fracture or broken bone. It became so problematic that we added a large dose of Calcium with Vitamin D to his daily medication regimen. However, no dose seemed enough, and too much Calcium can affect the heart.

Dad's doctors sent him to be tested for osteoporosis. A "bone scan" (Dual-energy X-ray Absorptiometry, or DEXA) was performed at a local hospital (as an outpatient procedure) and revealed that my father had, as the doctor called it, severe osteoporosis. I asked the doctor how "severe" it was, and he said it was a solid "9" or "10" on a scale of 1–10, and one of the worse cases he had ever seen. The medication that was necessary to combat osteoporosis that severe (Forteo®) was very pricey, and we could not afford it because Dad's Medicare coverage refused to pay for any portion of it. (The cost was about USD $3500 per month, and the usual treatment is an injection every day for two full years.) So, we sought assistance through the Veteran's Administration (VA). After a long six-hour drive to the nearest VA Hospital and back, plus a consult with their orthopedic specialist, they helped us to get it at an affordable price! Many thanks, VA! As my father's caregiver, I had to inject him with the medication every day. After a few months, he fell again but broke nothing, so the medication must have been working, thankfully!

Anemia...

Another symptom of PXE is anemia. The body transports oxygen throughout the body by means of a protein called hemoglobin, which is the main component of red blood cells. Anemia is characterized by a low amount of hemoglobin or red blood cells. The lack of sufficient oxygen to tissues that need it can cause anemia to be a very serious condition.

Most commonly, people with anemia report feelings of weakness or fatigue, and sometimes poor concentration. They may also report shortness of breath on exertion. In very severe anemia, the body may compensate for the lack of oxygen-carrying capability of the blood by increasing cardiac output. The patient may have symptoms related to this, such as palpitations, angina (if pre-existing heart disease is present), intermittent claudication of the legs, and symptoms of heart failure. [source]

Fortunately, my father never had cancer. However, many people with cancer, especially those who are taking chemotherapy, also suffer from anemia, so oncology clinics are equipped to handle anemia. Certain medications, such as Aranesp® and Procrit® can boost the body's ability to create hemoglobin-rich red blood cells. My father received periodic injections of Aranesp® to keep his anemia in check. He seldom reached a "perfect" score of 13 on his hemoglobin measurement, but the injections kept it in an acceptable range (usually 9–11). These medications are pricey, too, but Medicare covered 80% of the USD $3000+ injection required every eight weeks or so, and Dad's supplemental insurance covered the remainder.

Thin Skin...

Despite the thickening of skin around the neck, elbows, knees, and other joints, the skin in other places becomes papery-thin, especially on the lower arms, hands, lower legs, and feet. This led to my father's skin frequently tearing and bruising in those areas, and when I say "tearing," I mean that literally, as pieces from the top-layer of skin (the epidermis) would actually become separated from the next-lower layer (the dermis). Anyone who wants to see photos of such — not for the squeamish! — can click here to see examples.

Most of the skin tears happened when my father was doing some physical labor, such as tightening a bolt with a wrench and it slipped, or when he fell. Sometimes, though, he would have a skin tear and not even know when, or how, it happened.

Treating such a tear of the skin can be problematic and difficult, especially if not done correctly. One time in particular, my father and I tried to treat such a skin tear at home, but it wasn't healing, even after a couple of weeks of daily care. I took Dad to his Primary Care doctor who sent him to the outpatient Wound Care Center at the local hospital. I learned from them that repeated cleansing of such a wound, especially with off-the-shelf treatments such as Hydrogen Peroxide, can actually undo healing that the body is attempting. In this particular case, the wound was still open and painful after 13 weeks of their expert care and many different methods of treatment were attempted before even the Wound Care specialists began to see results.

Only one possible benefit...

Despite the havoc that PXE can wreak all through the body, there is one strange phenomenon that seems to be the only potential benefit of the disorder. At one of his appointments with a doctor, a deficiency was noted in blood flow through the carotid arteries in Dad's neck which supply oxygen to the neck, face, and brain. The doctor ordered a Carotid Vascular Study to be performed to see how bad (and where) the restriction was located. Such a test is relatively quick (20–30 minutes) and is done via ultrasound equipment by a Radiologic Technician.

My father asserted to the doctor that it was his understanding that in patients with PXE, the body sometimes creates alternate pathways for blood flow when a narrowing of the artery occurs. Still, my father had the Carotid Vascular Study performed. The results concurred with what my father had stated, that a small "web" of capillaries had formed adjacent to the artery, essentially bypassing the narrowing and compensating for the partial restriction! I was astonished and recall that the doctor seemed surprised, too. My father indicated that his twin brother had also undergone the same effect several years prior.

No cure... ☹️

Emory University's School of Medicine has been doing much research over the years into PXE as well as other diseases and disorders, trying to find a cure. Unfortunately, no cure exists thus far. However, I would advise anyone with a positive diagnosis to contact Emory University's School of Medicine because doing so could provide other resources about which I might not be aware, and documentation of your own condition could assist them in their research.

My uncle visited Emory and was examined by doctors in the School of Medicine back in the 1980s or 1990s, and it gave them additional information which they found extremely valuable. He was also examined by doctors and then presented to a class of medical students at the University of Florida's College of Medicine, which furthered their education about the disorder.

Other resources for information, assistance, and commiseration can be obtained at PXE International and The National Association for Pseudoxanthoma Elasticum (NAPE).

I received quite the medical education while caring for my parents in their final years. Having always been a geekette about the sciences, coupled with a desire to understand and provide the best possible care, I absorbed everything like a sponge and frequently did my own research online after returning from the doctors' offices. I would hope everyone reading this would do the same if found in similar circumstances, serving as caregiver to a family member.

The most heartbreaking thing about it all was watching my Dad, once strong, vibrant, and hard-working, stripped of so much of his independence and dignity. But, such are often the ravages of aging. 😔

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░░░░   THE END (finally, at 3648 words)   ░░░░

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SOURCES
    ¹ Dorland's Medical Dictionary: Systemic
    ² Farlex Partner Medical Dictionary: Pseudoxanthoma Elasticum
    ³ GENASSIST, Inc: Pseudoxanthoma Elasticum
    ⁴ MedicineNet.com: Pseudoxanthoma Elasticum (PXE)
    ⁵ Merck Manual: Pseudoxanthoma Elasticum
    ⁶ National Association for Pseudoxanthoma Elasticum (NAPE)
    ⁷ National Organization for Rare Disorders: Pseudoxanthoma Elasticum
    ⁸ PXE International
    ⁹ US National Institutes of Health: Pseudoxanthoma elasticum
   ¹⁰ Wikipedia: Angioid Streaks
   ¹¹ Wikipedia: Pseudoxanthoma Elasticum