Blau syndrome is an autosomal dominant genetic inflammatory disorder which affects the skin, eyes, and joints. It is caused by a mutation in the NOD2 (CARD15) gene. Symptoms usually begin before the age of four, and the disease manifests as early onset cutaneous sarcoidosis, granulomatous arthritis, and uveitis. Presentation
Cause
The elucidation that the gene defect in Blau syndrome (BS) involves the CARD15/NOD2 gene has stimulated many investigators to define how this gene operates as part of the innate immune system. The innate immune system recognizes pathogen-associated molecular patterns (PMAPs), including bacterial polysaccharides such as muramyl dipeptide, via its pattern recognition receptors (PRRs), such as NOD2, to induce signaling pathways that activate cytokine responses and protect the organism. In BS the genetic defect seems to lead to over activation and poor control of the inflammatory response leading to widespread granulomatous inflammation and tissue damage. Diagnosis
Treatment
Treatment has included the usual anti-inflammatory drugs such as adrenal glucocorticoids, anti-metabolites and also biological agents such as anti-TNF and infliximab all with varying degrees of success. History
In 1981, Malleson et al. reported a family that had autosomal dominant synovitis, camptodactyly, and iridocyclitis. One member died of granulomatous arteritis of the heart and aorta. In 1982, Rotenstein reported a family with granulomatous arteritis, rash, iritis, and arthritis transmitted as an autosomal dominant trait over three generations.In 1985, Edward Blau, a pediatrician in Marshfield, Wisconsin, reported a family that over four generations had granulomatous inflammation of the skin, eyes and joints. The condition was transmitted as an autosomal dominant trait.
These cells are grown in large numbers in a laboratory and returned to the patient after a treatment that temporarily reduces normal T cells in the patients body. TIL therapy following lymphodepletion can result in durable complete response in a variety of setups.The second treatment, adoptive transfer of genetically altered autologous lymphocytes, depends on delivering genes that encode so called T cell receptors (TCRs), into patients lymphocytes. After that manipulation lymphocytes recognize and bind to certain molecules found on the surface of melanoma cells and kill them.A cancer vaccine showed modest benefit in late-stage testing in 2009 against melanoma. BRAF inhibitors
About 60% of melanomas contain a mutation in the B-Raf gene. Early clinical trials suggested that B-Raf inhibitors including Plexxicons vemurafenib could lead to substantial tumor regression in a majority of patients if their tumor contain the B-Raf mutation. In June 2011, a large clinical trial confirmed the positive findings from those earlier trials.In August 2011 Vemurafenib received FDA approval for the treatment of late-stage melanoma. In May 2013 the US FDA approved dabrafenib as a single agent treatment for patients with BRAF V600E mutation-positive advanced melanoma.Some researchers believe that combination therapies that simultaneously block multiple pathways may improve efficacy by making it more difficult for the tumor cells to mutate before being destroyed. In October 2012 a study reported that combining Dabrafenib with a MEK inhibitor trametinib led to even better outcomes.