Blau syndrome has what is called a triad of classic symptoms. That just means there are three things most commonly seen in people with Blau syndrome, and these are:

• Granulomatous dermatitis: granuloma is a fancy word for a lump and dermatitis is inflamed skin, so you have lumps with skin inflammation, which is essentially a variation on the rash theme of other autoinflammatory diseases.
• Arthritis: joint swelling and pain, ‘arthron’ is Greek for joints and -itis is the medical suffix for inflammation, also of Greek origin, but via Latin.
• Uveitis: we say eye inflammation, but uveitis is literally 'inflamed uvea', it’s the bit of the eye between the sclera and the retina, where the vasculature is.

Because Blau syndrome is associated with early onset sarcoidosis, let’s also break that down. Sarcoid is derived from Greek meaning ‘flesh-like’ and -osis is another medical suffix that means ‘disease’. Sarcoidosis is used to describe a condition involving clusters of granulomas, among other systemic inflammatory symptoms. Early onset sarcoidosis is sometimes referred to as sporadic Blau syndrome.

Constitutional symptoms such as fever, fatigue and general malaise may also be present in Blau syndrome as inflammation develops a positive feedback loop over time.

Disease-causing variants in the NOD2 gene cause Blau syndrome. This gene sits on chromosome 16, which is an autosome, as opposed to a sex chromosome. And only one copy of the gene with the disease-causing variant is needed to have Blau. This is why inheritance is said to be autosomal dominant.

The NOD2 gene provides instructions for the body to make the NOD2 protein. (NOD2 gene italics. NOD2 protein no italics. Rules of science.) The NOD2 protein is involved in innate immunity. Beyond that it’s not really known how NOD2 causes the disease. It could be as simple as the NOD2 protein being bent out of shape because of the change in it, which could cause other immune cells to come along to try and section it off, effectively censoring it, themselves then creating the granulomas, which are clusters of immune cells. This is not a fact; it’s just a hypothetical scenario of how these clusters can potentially occur. The immune system’s ‘solution’ itself becomes the problem.

Blau syndrome can be diagnosed by a genetic test in patients who are displaying the symptoms associated with Blau.

A paediatrician or paediatric rheumatologist will usually take a patient through a process of ruling out infections and other conditions before determining that the patient may be a candidate for Blau syndrome and arranging for genetic testing.

Juvenile idiopathic arthritis is a different condition with similar symptoms that will likely be considered, and tuberculosis is one example of an infection that can result in the formation of granulomas.

It is important to follow up promptly throughout this process, as time is of the essence and delays in diagnosis and starting treatment can have devastating consequences.

Blau syndrome is treated by biologics that target TNF-α (e.g. adalimumab, infliximab).

While Blau is not considered an IL-1 mediated disease, this pathway is likely to become activated in the inflammatory loop that occurs in Blau and so anakinra may be useful in cases where TNF inhibitors are not suitable. Tocilizumab may also be useful and there is low-level evidence to support the use of tofacitinib in some cases.

Corticosteroids or low-dose methotrexate may be used in the early stages of treatment, but these are generally inadequate in controlling uveitis (which can lead to vision loss) and early transition to biologics is essential. They may be continued in combination with the biologics at the discretion of the practitioner. For pain management, non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and naproxen are most commonly used.

Blau syndrome is a serious condition that can have devastating impacts if not diagnosed and treated early. Because some of the symptoms can be non-specific, intermittent and develop slowly over time, sometimes patients are seen as having an infection or a reaction to something that will pass. Parents may be told their child will grow out of it. It is important to continue to seek medical advice if symptoms persist.

With appropriate treatment, kids with Blau can develop normally and expect a much better quality of life as a result. However, life for kids on biologics can be challenging on a number of levels:

First is the treatment itself, which involves normalising needles that are either self-administered or given by infusion.

Second is that these biologics can sometimes stop working because the body’s adaptive immune system detects them as foreign and makes antibodies against them, rendering them ineffective.

Third is that people on biologics need to take extra care in situations where they may be exposed to infections. This is true for anyone with an autoinflammatory condition, treated or not.

Infections pose a higher risk for kids (and adults) with Blau, just by the fact that they have an immune system that works a bit differently from the general population. This can be especially tricky for children during their social development but it’s important to pay attention to this. Education and awareness can help the patient, their family, friends and the community for the best possible outcome.

Ongoing monitoring becomes a part of life for children and adults living with autoinflammatory diseases, and regular reviews are scheduled with specialists.