Inflammatory processes are normally strictly controlled and serve an adequate defence reaction regarding e.g. microorganisms. Without this function the physical integrity of the individual would suffer. However, if a disturbance of the immune regulation occurs due to circumstances that are not yet clearly clarified, this can lead to various malfunctions:
- an ineffective immune response, or
- misdirected exaggerated immune response
In this case, a manifestation in the form of autoimmunity (autoimmune diseases such as rheumatoid arthritis) or autoinflammation (autoinflammatory disease such as Adult Still's disease) will happen.
The clinical picture of an autoinflammatory disease can be presented by intermittent, but sometimes also by a persistent systemic inflammatory reaction. This is usually associated with self-limiting fever episodes, which often begin very acutely. The fever episodes can be accompanied by variable organ manifestations, such as arthralgias, myalgias, polyserositis, skin exanthema, lymph node enlargement and gastrointestinal complaints. Laboratory chemically, a non-specific increase in acute phase proteins, such as C-reactive protein (CRP), blood cell sedimentation rate (BSG), ferritin or serum amyloid A, without detection of specific autoantibodies is impressive. In the intervals between the attacks, many of those affected are symptom-free, but even then, elevated levels of serum amyloid A may be present, which increases the risk of developing amyloidosis. Many of the autoinflammatory diseases are monogenic (Familial Mediterranean Fever (FMF), Tumor Necrosis Factor Receptor-1 Associated Periodic Syndrome (TRAPS), Hyper-IgD Syndrome (HIDS) and Periodic Fever Syndrome (PFAPA)). Polygenic inheritance patterns have also been found in some autoinflammatory diseases: gout, adult Still's disease, pseudo-gout, diabetes mellitus type 2, Crohn's disease.
The innate immune system plays a key role in the development of these pathologies. Interleukin 1 [IL-1] represents the central cytokine for the central symptom - fever. At the same time, however, other signalling cascades are set in motion, leading to the completion of the clinical picture of various auto-inflammatory syndromes.
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