Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated Temperature (CANDLE) Syndrome
Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated Temperature Syndrome (CANDLE Syndrome) is a very rare autoinflammatory disease that was classified in the past few years. In the past, the disease was referred to in literature as Japanese Autoinflammatory Syndrome with Lipodystrophy; Joint contractures, Muscle atrophy, Microcytic Anemia, and Panniculitis Induced Lipodystrophy (JMP); or Nakajo-Nishimura Syndrome(NNS). It is estimated that there are at least 60 known cases of CANDLE, but likely many more cases that are undiagnosed, or diagnosed as having other conditions. Now that the classification of this syndrome has been better established, and the genetic cause identified, there will likely be more cases discovered in the world.
Patients first present with recurrent fevers that begin in infancy, and occur almost daily. They also have delayed physical development, purpuric skin rash, and unique facial features. The patients have thicker lips, swollen purplish-red (vioacerous) eyelids, and also lose a lot of their fat on their face (lipodystrophy). Patients with CANDLE can also have conjunctivitis, arthralgia without arthritis, nodular episcleritis (irritation and inflammation on the tissue covering the white part of the eye), chondritis of the ear and nose (inflamed cartilage), episodes of asceptic meningitis and systemic inflammation. Children can also develop periorbital edema (swelling around the eye sockets), and edema (clubbing) of finger and/or toes, and gradual enlargement of the liver, along with a decrease in muscle mass and peripheral body fat. Later in life, patients may develop joint contractures, cardiac arthythmias (alterations in the heart rhythm), and dilated cardiac muscle, which is very concerning.
These patients often present with low height and weight, developmental delays, enlarged livers (hepatomegaly) and often have chronic anemia, elevated liver enzymes and elevated acute phase reactants on lab tests.
Recently, genetic studies have identified PSMB8 gene mutations in most patients with CANDLE syndrome. The PSMB8 gene is involved in the encoding of over 20 components that make up proteasomes in the cells. Proteasomes recycle proteins that are produced by stressed or dying cells. In patients with CANDLE syndrome, the mutation in PSMB8 causes protein waste products to accumulate, since there is a malfunction of the proteasomes in cells throughout the body.
In addition, testing revealed a unique interferon (IFN) signature on microarray profiles and monocyte stat-1 activation studies that are unique to CANDLE syndrome, as they are not present in other autoinflammatory diseases. It is theorized that dysregulation of the IFN singnalling pathway may be a leading cause of the inflammatory response in patients with this disease. Currently research is being done at the National Institutes of Health (NIH) with IFN signalling inhibitor medication JAGA LY 3009104.
Here is a really nice video about a patient with CANDLE, and we are thankful that they have shared this for others to see. Please watch it.
For more information. please refer to this article that was published on January 20, 2012 in the American Journal of Medical Genetics, which we have used as a reference for the information above. http://onlinelibrary.wiley.com/doi/10.1002/ajmg.a.35225/pdf