What is Blau Syndrome?
Blau syndrome (BS) (also called Early-onset sarcoidosis (EOS)) is a rare systematic inflammatory disorder that usually begins in early childhood with symptoms presenting before the age of 4. It is a genetic illness, although it is not always inherited (such was the case with Lexi) and is a result of a mutation in the NOD2 gene. There are several variants, each with differing symptoms. Lexi's variant C495Y seems to have been one of the rarest of all. We are only aware of 3 other patients in the world with this variant making it even more complex to understand and treat.
What are Blau Syndrome Symptoms?
Blau syndrome is a progressive disorder and while it presents in many different ways, it commonly affects the skin, joints, and eyes. We hope that by going into more detail of the symptoms Lexi had experienced, we can help others with early diagnosis and for those who are already diagnosed, to have a better awareness of what they might look out for. From what we know now, early detection and treatment are crucial for improved outcomes. Some patients with Blau have found treatments that manage their symptoms. For most the remissions seems to be temporary as the body eventually rejects the treatment. Unfortunately, many have yet to find a medication that is effective, which had been the case with Lexi. She had trialed and failed several medications.
A rash often presents with small hard micro-papular lumps under the skin (granulomatous dermatitis). This is how Lexi was diagnosed. She was referred to a dermatologist that recognized the rash, which was biopsied and confirmed as a granuloma. From there we were sent for genetic testing to confirm her diagnosis. When Lexi was younger the rash was red and looked more like an allergic reaction of some kind. She was originally diagnosed with food allergies. Lexi's rash had changed from a skin-coloured, raised rash to a scaly reddish-coloured rash.
Polyarthritis (arthritis affecting more than five joints simultaneously) appears in over 95% of cases of Blau Syndrome. It causes swelling and joint pain. Synovitis, inflammation of the synovial membrane, can appear in the joints of the wrists, knees, hips, ankles and shoulders. The back of the wrists and knees are common spots for pockets of synovial fluid to form and this is commonly described as "boggy" arthritis, as shown in the image above. As the condition progresses range of motion in the joints is restricted. Tenosynovitis, inflammation of the tendon sheaths, is commonly noticed in the hands, fingers, wrists, feet and toes and is very painful.
Over 80% of those with Blau syndrome also develop uveitis, inflammation of the uvea. It is usually bi-lateral (in both eyes) and is most commonly panuveitis (the inflammation affects all layers of the uvea). It can also affect the lens, retina, optic nerve and vitreous causing reduced vision or blindness. Uveitis is one of the most concerning symptoms of Blau syndrome and must be closely monitored by an Ophthalmologist. Lexi's first sign of panuveitis started when she was five and a half, after having a minor flu. She woke up with redness in her eyes said they were sore. It can be tricky to identify as symptoms are not always visible without a slit lamp examination. Before Lexi was diagnosed with panuveitis, we had visited her Ophthalmologist every three months for checkups.
Some patients with Blau syndrome develop kidney disease. They may also have nephrocalcinosis (deposits of calcium in the kidneys) which can lead to chronic kidney failure. Inflammation of blood vessels (vasculitis) can cause scarring and tissue death in the vessels and impede blood flow to tissues and organs.
Less commonly, Blau syndrome can affect the liver, spleen, salivary gland, brain, blood vessels, lungs, and heart. Inflammation involving these organs and tissues can cause life-threatening complications.
Because of the progressive nature of the disease, we were always on the lookout for new symptoms. Since she was very young, Lexi had gastric issues - severe bloating and pain in her stomach. Recent biopsies had found granulomas in her intestines. When she was 4, her parotid glands became enlarged and impacted her saliva production. At one point her glands were the size of golf balls on both sides of her face and under her chin. We had recently found out that Lexi's vocal glands have also been impacted which explained her high-pitched voice. Lexi's growth had been severely stunted and she was showing early signs of osteoporosis. Her frame was very tiny and her limbs were especially frail. Lexi had frequent headaches and experienced periods of daily fevers.