- CASE FILE
Connective tissue disease, blindness, JRA, chronic neuropathy, Marfan’s, birth defects, Dupuytren's, subluxing joints, chronic infections
ABOUT THIS CASE FILE
Deb: Hello from Alaska!
My name is Debra Wozniak and my kiddo, Delaney, and I have both had a lifetime of medical craziness. Delaney’s pediatrician said to us, “Every Doctor has seen something incredibly rare in their careers and for me, that is you, Delaney.” So, from that point on, we made it our mission to see as many doctors as possible. We figured, the more eyes on Delaney the better. Maybe, just maybe, their super rare patients will match up with my super rare Delaney.
Delaney and I have been navigating this road of medical ambiguity since 2007 when Delaney was just 9 years old. Let's start with her story first.
When Delaney was very young she started to grow excessive tissue on her eyes. At first, it was diagnosed as “Pterygiums”, however, everytime the tissue was removed, it grew back within a month. Imagine this poor kid going blind, then regaining her sight, only to go blind again within a month!
It was devastating. The poor kid had to endure that heartbreak after each of the 4 failed surgeries. Each time the tissue grew back more aggressively and was webbed with scar tissue. She had finally gone completely blind. Her eyes turned whitish-blue. People called her “zombie” and cruel things like that. However, Delaney continued her relentless pursuit to succeed. She learned how to read braille and use a cane to orient herself. She began using adaptive equipment at her high school. Delaney was even spotlighted by one of our local news stations, KTUU, during Disability Awareness Month in 2014 as an exemplary representative of our disabled community.
At the same time Delaney was going blind, she began to manifest a multitude of complex medical abnormalities and was sent to Seattle Children's Hospital where she was a patient for six years. After being thoroughly reviewed by the medical teams at Seattle Children's, Delaney's pediatrician referred her to the NIH undiagnosed diseases program citing the following medically complex history:
Per Delaney’s Pediatrician’s referral to NIH (which was denied):
Delaney has an undiagnosed form of connective tissue disease, clinically manifesting as joint hypermobility, translucent skin, thickened pads over her knuckles, easy bruising, eye/vision problems and chronic paresthesia. She has been evaluated primarily at Seattle Children's Hospital by genetics, rheumatology, dermatology, ophthalmology, and allergy/immunology. Some of these problems were noted at birth and early childhood, and have generally become progressively worse. She has recurrent joint pain and paresthesias which can be debilitating. This pain occurs in upper and lower limbs, palms, knees, ankles and soles of her feet. Her pain is worse with activity, but no other specific triggers have been identified (e.g., stress, infections);... Per rheumatology, she does not have evidence of actual arthritis. She wears AFOs during the day, as well as wrist braces at night to help minimize any possible damage to her joints due to subluxation. She has had multiple eye surgeries due to progressive pseudopterygium in both eyes; this has progressed into the corneal on both eyes. She also has corneal neovascularization. She has very poor light and color perception.
There is discussion of a corneal transplant planned at some point, but her ophthalmologist is hesitant to do surgery in light of the uncertainty of her underlying condition. She has been evaluated for possible Marfan's syndrome. She fits some but not all criteria and has a normal ECHO. She has had recurrent sinusitis, and has had sinuplasty with some improvement in the frequency of her episodes. She has recurrent oral lesions diagnosed as aseptic aphthous stomatitis, which seem to respond to valacyclovir. She has been followed by allergy/immunology for asthma, allergic rhinitis and her recurrent infections (primarily sinusitis, occasional pneumonia and OM)
In December 2013, she had a flu vaccination which led to a few weeks of recurrent fevers and myalgias; her exam remained unchanged and these symptoms persisted for 3-4 months.
She again underwent a comprehensive evaluation at Seattle Children's. Due to her recurrent fevers, she has also been referred for further immunology evaluation.
Del: Hey there! Delaney here. Below is a little more detail on specific specialties that I’ve seen and what we’ve learned from them.
ALLERGY/IMMUNOLOGY: Diagnostic testing has not provided any clues on what may be causing this. However, it is noteworthy that my pneumococcal titers were so high that the test equipment of three different hospitals were unable to count them, these being the MAYO Clinic, the University of Washington Medical Center, and Providence Hospital. During this time I was also evaluated for pneumonia, which I did not have. I am allergic to mold spores, dust mites, and milk protein.
RHEUMATOLOGY: I have a negative Rheumatoid Factor. Any arthritis-like symptoms I am currently experiencing seem to be caused by repeated injury to joints from subluxation. However, my mother has Juvenile Rheumatoid Arthritis and at the height of her joint erosion she had a negative Rheumatoid Factor as well.
CARDIOLOGY: In addition to the usual battery of tests that go along with a Marfan’s diagnosis, I was also evaluated over a period of three months with a halter monitor for unexplained bouts of rapid heart rate and palpitations, climbing into the mid-100s at rest, and in the very high 100s with moderate to vigorous activity, with some of the latter entering the low 200s. Results of the test were inconclusive. The doc I saw believes that I may have Premature Ventricular Contractions, which they said are not a danger to me so long as I feel okay during the time these spikes happen.
ORTHOPEDICS: As mentioned above, all of my joints are incredibly loose and very easy to sublux or dislocate. I have fractured both ankles before and sprained them multiple times, broken the 5th toe on both feet, fractured my left wrist and sprained both wrists several times, and have two ribs on the left side of my chest that repeatedly dislocate and snap back into place, particularly when I have a cough or am doing strenuous upper-body work. Additionally, my fingers are extremely easy to sublux and I have to be very careful when lifting heavy things or climbing. I do have mild scoliosis, but it is well controlled with specific exercises and stretches. I also have very flat feet and wear braces any time I will be walking for longer than a few minutes. These are both to correct the issue of plantar fasciitis and also to protect my ankles from subluxation, which happens often when I am simply just walking around.
INFECTIOUS DISEASE: Although recently they have been less severe, I have recurrent infections that ID believes may be related to some sort of autoimmune disorder. We have no concrete evidence of this at this time, as Immuno diagnostics did not point to any specific cause. I was previously MRSA colonized after multiple hospital stays for infections requiring IV antibiotics. I have had dozens of sinus infections, as well as frequent bouts of strep and pneumonia when I was a child. After a sinuplasty was done, the sinus infections lessened. I have also had a few skin infections and one joint infection on the ring finger of my right hand, which was not the result of injury and was bad enough to require IV antibiotics and surgical intervention. Additionally, the first and only attempt to correct the healing of one of the aforementioned broken toes resulted in a bone infection and debilitating pain that put me in a wheelchair for a little over 8 months. Once I could start walking again it took me several years to build up my strength and stamina again.
DERMATOLOGY: I have had two biopsies done of the thickened pads over my knuckles, both of which were evaluated and determined to be excess collagen that winds itself around the tendon. My skin is very thin, translucent, and bruises easily. This is likely due to some malformation of collagen, though we have yet to find concrete evidence of this. The bruising can happen with very little force applied, and sometimes they occur completely on their own without any touch applied (My mother and I tend to call this “exploding veins.”) When this happens, a large blue lump of blood forms in the area. It is incredibly painful until the blood begins to spread throughout the surrounding tissue. Then, the site of the exploded vein appears normal, yet an enormous bruise surrounds the entire area. Some bruises have been the size of watermelons. People have often been concerned that we are being abused. We try to explain that we have not done anything to cause the bruise, that it appears on its own, but unless you witness it happen, it’s pretty hard to believe. There is a type of Ehlers-Danlos Syndrome where people experience exploding organs in addition to similar bruising, but my mother and I have been tested genetically and thankfully we are negative of all types.
GENETICS: Both my mother and I were evaluated at UW Medical Center’s genetics clinic by the head of the department. As mentioned, they did tests for Ehlers-Danlos and all were negative. I was also tested for Loeys-Dietz, which was also returned negative. My doc sequenced the Collagen 3A1 gene, looked for mutations, deletions and duplications. However, nothing noteworthy was found and at the time these tests were performed they did not have any other places they wanted to look. They are, however, so sure that both my mother and I have Marfan’s Syndrome that they did not test for it.
OPHTHALMOLOGY: Okay, this is the most important one. In 2007, I was diagnosed with pterygium tumors on my right eye, and had the excess tissue removed four times between 2008 and 2011. During this time, the diagnosis of Pterygium tumours was the closest matching affliction to what I was experiencing. In 2012, my vision worsened significantly. Rather than perform a 5th surgery on this diagnosis, my primary Ophthalmologist referred me to the Ophthalmology department at Seattle Children’s Hospital. Unfortunately, they had no further answers for me, and from 2012 to 2014 I lost nearly all of my vision. I could only see light and dark at the worst point, no color, text, etc. It was at this point that my mother and I began looking for clinical trials, research studies, anything we could find that was relevant to my issues. This eventually led us to being referred to the Harborview Medical Center Eye Institute. I was seen by the head of the department, who said that they have only ever seen one other person with similar eye findings, and she was also a teenage girl. We were given a new diagnosis- Total Limbal Stem Cell Deficiency. The way it was described to us was that there is normally a ring of stem cells between the cornea and sclera (the white part of the eye). This helps keep the cornea clear and prevent the overgrowth of scleral tissue into the visual field. For myself and my mother, that ring of cells does not exist. Thus, the white of the eye overgrows the cornea relentlessly. As you can see in the pictures, my mother’s eyes have not had any surgeries thus far because the docs are worried the same outcome will happen to her sight that happened to me. Her symptoms started more recently in terms of vision and have progressed much faster than mine. Since then, My doc in Seattle has tried twice to surgically intervene and return my sight. Both times they used an amniotic membrane graft, this time on my left eye, which had also become symptomatic at this time. But like the previous attempts, these also failed. The later procedure also caused complications, and my lower left eyelid fused itself to the surface of my eye with scar tissue. This had to be rectified with another procedure to disentangle the two, and while it did take well and make me much more comfortable, it did not improve my vision whatsoever. Currently, my mother is suffering through the same problem, however, hers is not related to surgical complications. Our Ophth team is hesitant to remedy the issue, due to the severity of scarring that resulted from my own procedures. The improvements that have been made to both of our sight have been done with the use of scleral contact lenses. These are cereal-bowl shaped lenses that are filled with saline or another lubricant and suction cupped to the sclera, not the cornea like normal contacts. This enables the lubricant to smooth over some of the scar tissue, reducing the kaleidoscope effect it has on our vision, while also keeping it hydrated and reducing irritation. While I am still legally blind even with the lenses, my comfort level has greatly improved and I can read large-print text. Without them, I have no vision at all, which is terrifying to deal with whenever I have to go without the lenses for any length of time. Additionally, they are highly expensive, starting at $500 per lens. They are not covered by our insurance and we have had to purchase 9+ lenses because of the rapid changes in both our vision and the shape of the scar tissue on the surface of the eye.
In addition to the issues mentioned above, my mother also has at least two granulomas growing outward from the surface of her eye. This is noteworthy because I do not experience this issue. She has had them removed once, but like my procedures, the tissue grew back within the month, and her symptoms were worse off than before.
NEUROLOGY: I have been evaluated by neurology, but so far my mother has not. I had MRIs done of my brain, C-spine and T-spine, as well as testing for MS and other demyelinating diseases. Those tests were thankfully negative. With the information provided by the MRIs my doc diagnosed me with Chiari Malformation Type I, which is a birth defect that affects the structure of the cerebellum and it’s position within the skull. While normally, the spinal cord is the only thing to extend into the foramen magnum, in my case the cerebellum occupies part of this space. However, my doc believes this is unrelated to my chronic neuropathy and paresthesia. At present we have no theories on what may be the cause.
PAIN CLINIC: I was seen by a pain management team starting in 2013 at Seattle Children’s Hospital. The doctors there theorised that my pain issues may be related to a phenomenon called Central Sensitization, but according to Neuro this is unlikely. I have debilitating neuropathy and paresthesia, currently being controlled as well as can be expected by Lyrica, which I have been on since late 2014. Prior to this I was on Hydrocodone, which did very little for the pain and made me incredibly anxious and hypersensitive to sound. In addition to medication., I was also taught to use meditation and biofeedback as a way of controlling my pain.
ADDITIONAL INFORMATION: I was a term delivery, complicated by birth depression requiring resuscitation. I had hand/feet deformities noted at birth.
SURGICAL HISTORY: Tonsillectomy and adenoidectomy, ethmoid/sphenoid/maxillary sinoplasty (2012). 4 eye surgeries for pterygium excision. Repair of post-traumatic L 5th hammer toe Oct 2013, 2 eye surgeries: excess tissue removal and attempts at regaining some vision (2015-2016), 1 eye surgery to remove scar tissue that fused the lower left eyelid to the surface of the eye (2017), septoplasty in attempt to repair deviated septum partially blocking airflow (2018).
Deb: Okay....back to my saga!
Let me tell you folks, so far I have had one crazy, fun, hilarious, No-way-you-are-making-that-up no-I-swear-it-really-happened kind of life! I mean, I could write a book! But as fun as it has been, it has at times also been my own personal hell. There is only one thing worse than watching your children suffer and be afraid. And thankfully I have never had to live through that. My son, Noah, was born with Mosaic Down syndrome and a bad heart. He had three holes in his heart and only one valve. Those first few months of his life were gut wrenchingly terrifying. I was afraid to walk out of the room. I was afraid to sleep. I was afraid that I would wake up and he would be gone. It was excruciating for our whole family. But by the grace of God, Noah pulled through and after his open heart surgery he thrived. Today he's a tank!
From a personal standpoint I usually keep the focus on the kids. I keep a lot bottled up inside me, because you have to be a positive influence in the lives of children who are suffering. However, Delaney and I really need your help. so I'm just going to let it fly!
RHEUMATOLOGY: Back in the day, kids didn't get Rheumatoid Arthritis. It wasn’t even on the radar for a kid my age. It was an “old people’s disease”. So, no one knew how much pain I was in. Every step was an experiment in torture. It still is. I wouldn’t wish my pain on my worst enemy. And may I say, being disabled back in the day was MUCH less supported than it is now. People were so heartless sometimes.
I thought I was a pretty normal kid. I played outside. I ate mud pies. I was a super “bendy” kid, just like Delaney. In fact, many of the symptoms that Delaney has described in her portion of this patient profile mirror my own childhood. I had hyper mobile joints. I had those weird growths on all my knuckle pads. My joints would sublux causing continuous sprains and dislocations. So, it's so weird that I ended up having lost so much of my mobility.
My earliest memory of experiencing intense pain was at 6th grade volleyball practice. After hitting the volleyball, I collapsed to the floor. I remember briefly blacking out. The pain was so intense that I could do nothing but lay there and try not to throw up. Up until that time, I had always experienced some level of pain, but I just thought that was normal. But after that day, whatever I had became incredibly aggressive. All my fingers started to swell up and become hot and red and stiff. I started to grow nodules on all my knuckles.
My parents took me to doctor after doctor after doctor. My joints were deteriorating so rapidly that at one point the docs feared I had cancer. So we were very thankful to find out it was only Juvenile Rheumatoid Arthritis. When I say that we were thankful that it was only JRA, I am not negating the suffering that that evil disease wreaks on people's bodies. The best way I have found to describe the pain that accompanies rheumatoid arthritis is to imagine the worst toothache pain you have ever experienced. A toothache that is so bad that there is nothing that you can do to dull the pain. you can't stop thinking about it, Now imagine that pain in every part of your body and it never goes away. It takes away your will to live. It almost did mine. A wise doctor finally diagnosed me with JRA at 14 years old.
GENETICS: UW Medical Center had this to say about my case…
Debra has a more complex clinical picture. When she was younger, she had marked joint hypermobility and indicates that she thinks that her skin was very much like her daughters with increased bruising and increased venous visibility. She had in addition developed juvenile rheumatoid arthritis and was treated with a variety of medications including anti-inflammatory and steroids as well as methotrexate. Over time, she has developed constriction in the movements of her hands and also of her feet and has had a fusion of some of the bones in her fingers and the development of the Dupuytren contractures on both sides. Over time, she has had multiple skin infections and appears to have infection several times a year including sinus infection. She has not been evaluated extensively for this or at least there is no clear definition of the reason for why she bruises easily. She has had a change from having marked joint hypermobility to stiffness of her joints with the progression of the arthritis. She has not had significant cardiac disease, has been evaluated by echocardiography in the past and has a normal aorta and no evidence of other vascular abnormalities. She has a striking family history and other abnormalities among her children She has a seventeen year old son who has Mosaic Down Syndrome, and an eighteen year old daughter with Autism.
OPHTHALMOLOGY: Like Delaney said in her portion, the working diagnosis for both of us is Total Limbal Stem Cell Deficiency. Unlike my daughter, for a very long time my eyes were irritated, but I did not lose my vision. That has changed very recently and very quickly. Without anybody performing surgery on my eye, my lower eyelid has fused to the surface of my eye just like Delaney’s did. The tissue on my eyes also seems to be thicker than hers too, and I do not get as much relief using the scleral contacts as she does.
It is so thrilling to see that we now have a safe place where we can support and be supported by people like us. Delaney has been examined by roughly 100 medical professionals and as one doc said, ”all we can do is just stare off into space and scratch our heads.” We are proud to join ranks with all of you beautiful people to help bring an end to our collective suffering. With Ann Curry leading our pack, these mystery illnesses don’t stand a chance.