Quite a few people suffer lifelong regularly occurring fever and inflammation attacks with no apparent reason. For a long time, doctors were unable to decipher the reasons for such periodic fever syndromes. However, the identification of the genetic causes of the syndromes has in the meantime led to the identification of the metabolic pathway involved as well as to targeted therapies. Effective treatment has greatly improved sufferers’ quality of life. In addition, insights into the development and treatment of periodic fever syndromes have also led to the development of new strategies for the treatment of diabetes mellitus and gout.
Dr. med. Jasmin Kümmerle-Deschner, senior physician in the Department of Paediatric Medicine at the University Hospital of Tübingen, recalls only too well the first patient that she diagnosed with Muckle-Wells syndrome (MWS), a rare autosomal dominant disease. The girl was suffering from recurrent fever attacks, skin rashes, conjunctivitis and painful joints. The initial diagnosis of rheumatic fever could not be confirmed. The fact that the patient, along with numerous other members of her family, suffered from pronounced deafness, eventually put the head of the paediatric rheumatology outpatient department on the right track.
"Molecular genetic methods were used to ascertain that the girl had Muckle-Wells syndrome, and we then went on to identify the same disorder in twelve of the girl's relatives," said Kümmerle-Deschner. MWS belongs to the group of periodic autoinflammatory fever syndromes and is an autosomal-dominant disease, which is why it also occurs in family members that happen to carry the same defective gene. This discovery ended years of suffering for the patients in question as the fever and inflammatory attacks, which in the case of MWS are triggered by unspecific factors such as cold and stress, typically start during childhood. "The patients feel as if they constantly have a cold," said Kümmerle-Deschner going on to add, "this considerably reduces quality of life". As the disease progresses, many patients develop sensorineural deafness and reduced kidney function. "Many MWS patients need to undergo dialysis very young because the kidneys are unable to remove waste from the body," said Kümmerle-Deschner.
Interleukin-1β-mediated inflammatory reactions also seem to play a key role in many other diseases, including gout and type 2 diabetes mellitus. “It appears that uric acid crystals or elevated blood glucose levels also induce the production of larger quantities of IL-1,” said Kümmerle-Deschner. Initial investigations have shown that the blockage of IL-1β in people with severe gout leads to a considerable improvement in their condition. New drugs have been shown to have a positive effect on the regulation of the blood glucose level in diabetics as well as on the secretory function of insulin-producing cells. It can therefore be assumed that the anti-inflammatory IL-1 antagonists are likely to lead to promising outcomes in the treatment of such classical common diseases in the not-too-distant future.
Further information:Dr. med. Jasmin Kümmerle-Deschner University Children's Hospital TübingenOutpatient Department of Rheumatology and Autoimmune DiseasesDepartment of General Paediatrics, Haematology/Oncology (I)Hoppe-Seyler-Str. 1 72076 Tübingen Tel.: +49 (7071) 29-80901 Fax: +49 (7071) 29-4157 E-mail: Jasmin.Kuemmerle-Deschner(at)med.uni-tuebingen.de