Rare Disease Baffled Medics
Imagine you or a loved one is experiencing a few, or all, of the following symptoms: pain in the legs and arms, weight loss, muscle aches, excessive thirst, balance issues, reduced kidney function, vision difficulties, and shortness of breath. Can you imagine what the patient may be suffering from? Sometimes the patient may experience just the pains in their arms or legs, and sometimes they may have three or four of the symptoms all at once. These symptoms are indicators of dozens of possible illnesses, which makes diagnosis quite difficult. Is it arthritis, cancer, multiple sclerosis, or kidney disease?
David Friedlander was born and raised in Johannesburg, South Africa in 1954 before emigrating to Atlanta, GA in 1986. He was an athlete throughout his life and enjoyed being active on the field with his four sons well into his late 40's. In 2007, he began experiencing dizziness and as he reports, "loss of balance and sense of direction." Prior to that, he had also complained of "arthritic" like symptoms and difficulty sleeping due to stiff and sore legs. He also had a heart problem requiring stents, despite being healthy in all other aspects. When he began losing balance while sitting and walking, he took the symptoms more seriously and began seeing a full range of doctors and natural remedy specialists: ENTs, Immunologists, Infectious Disease Specialists, Orthopedists, Neurologists, naturopaths, chiropractors, to name just a few.
Even after an MRI revealed tumors on his brain stem, doctors were unsure of the type and cause of them.By 2012 David was unable to walk, experienced slurred speech, difficulty swallowing, and vision problems. Without a clear diagnosis, and with most of his family having moved to Israel, David moved to join his four sons and three granddaughters in Israel. To everyone's surprise, six months after arriving in Israel and after two brain biopsies, an explanation for the strange conglomeration of David's symptoms was found. Dr. Roei Mazor believed he was suffering from a rare slow-growing blood cancer called Erdheim-Chester Disease (ECD).
According to the ECD Global Alliance, "Erdheim-Chester Disease is an extremely rare disorder that can affect many different organs of the body.It is characterized by excessive production and accumulation of specific cells whose normal function is to fight infections.These cells, which are called histiocytes, infiltrate the loose connective tissue of the body.As a result, this tissue becomes thickened, dense and fibrotic.Multiple different organs can be affected.Unless successful treatment is found, organ failure can result."
The disease most often affects the long bones of the lower limbs, around the knees, leading to bone pain, which might progress to become debilitating. The impairment is caused by an infiltration of the bone marrow by histiocytes. Separately there may be damage to the pituitary gland which may lead to the Diabetes Insipidus and its associated symptoms. Patients may also suffer from Cerebellar Syndrome, which can result in loss of balance, vision focusing problems, movement difficulties, swallowing challenges and other neurological system problems.
There are only about 1,000 diagnosed cases of ECD worldwide and fewer than twenty cases in Israel. Yet dedicated patient referral centers in Israel offer state of the art diagnostic technologies and personally tailored biological therapeutics available for ECD patients, according to Dr. Roei Mazor, physician in charge of the Clinic of Histiocytic Neoplasms at Assuta Medical Center, Tel Aviv.
Sufferers of ECD usually report symptoms when they are in their late forties, but there are documented cases of the disease occurring in young patients. The disease ranges from a mild localized form to a severe, multisystemic life-threatening form. Prior health of the patient is not a determining factor for contracting ECD according to the ECD Global Alliance.
Diagnosing ECD can be difficult since the heterogenous symptoms mimic a variety of other diseases and conditions. The process may begin with the collection of a biopsy of the affected tissue. If the tissue contains specific pathological characteristics suggestive of ECD, a multi-modal global disease burden assessment will be performed to get a full scope of the disease and how it is affecting the body.
Treatment for Erdheim Chester varies by patient and severity of illness. A variety of treatment alternatives are being used on a patient by patient basis, depending on the molecular characteristics and severity of the disease. Since 2013, identifying and targeting the mutations that drive ECD have practically revolutionized the field with dramatic long-term disease regression documented in many patients.
Awareness of this rare blood cancer can mean earlier diagnosis and treatment for patients and help preserve better quality of life for those suffering from this condition. The earlier the disease is caught and stopped, the less damage can occur to vital organs such as the brain and quality of life can be maintained for decades.
Following his diagnosis, rigorous attempts to identify the mutation driving David's disease were made. However, this task proved difficult in the absence of sufficient pathological material from his former biopsies and since an additional brain biopsy was out of the question. Ultimately, a novel approach was fruitful – an attempt to isolate and test minute quantities of tumor DNA from David's urine was successful and a mutation in a known cancer driver, BRAF, was identified. This discovery enabled doctors to suit David with a personalized biological treatment regimen, designed to target the Achilles heel of the disease. Following therapy, the multiple tumors from which he was suffering nearly disappeared.
David's disease is now under control, thanks to a combination of Vemurafenib, which is a BRAF inhibitor, and Cobimetinib, a MEK inhibitor. Both drugs were developed to treat Melanoma but have shown to be effective in reducing the size of the tumors affecting David, according to Dr. Mazor. However, the late stage at which David was diagnosed left damage to his brain stem which makes quality of life difficult. He is bound to a wheelchair most of the day and cannot eat or drink through his mouth, as his swallowing reflex has been damaged. He has experience multiple cases of pneumonia as a result of aspirations and has had too many hospital stays to count. Despite all this, his current challenges have shifted from stopping the disease, nothing short of a medical miracle, to rigorous rehabilitation to restore some of his lost capacities. He maintains his unique sense of humor and never misses a day of physiotherapy, eagerly looking forward to the day where he can enjoy a waffle and ice cream again.
Those who suffer from the disease and the medical community researching it are working hard to raise awareness.
Acknowledgements:
We thank Dr. Roei Mazor for his invaluable contributions to this article for its medical accuracy, and for his unwavering care and treatment of David Friedlander over the past four years.
Thank you to Kathy Brewer and the ECDGA organization. Thanks to the ECDGA, we have a global medical community for ECD, we share knowledge, and this translates directly to patient care.
Special thanks to David Friedlander for agreeing to share his story with the world and for being an inspiration to all those who witness his immense strength and persistence to survive and thrive.
Early diagnosis is key to living a long and high-quality life with ECD. For more information, please visit:
https://rarediseases.info.nih.gov/diseases/6369/erdheim-chester-disease
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