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Background Little is known about the characteristics of patients seeking help from dedicated centers for undiagnosed and rare diseases. However, information about their demographics, symptoms, prior diagnoses and medical specialty is crucial to optimize these centers’ processes and infrastructure. Methods Using a questionnaire, structured information from 522 adult patients contacting a center for undiagnosed and rare diseases was obtained. The information included basic sociodemographic data (age, gender, insurance status), previous hospital admissions, primary symptoms of complaint and previously determined diagnosis. Results The majority of patients completing the questionnaire were female, 300 (57 %) vs. 222 men (43 %). The median age was 52 years (range 18–92). More than half, 309 (59 %), of our patients had never been admitted to a university hospital. Common diagnoses included other soft tissue disorders, not classified elsewhere (ICD M79, n = 63, 15.3 %), somatoform disorders (ICD F45, n = 51, 12.3 %) and other polyneuropathies (ICD G62, n=36, 8.7 %). The most frequent symptoms were general weakness (n = 180, 36.6 %) followed by arthralgia (n = 124, 25.2 %) and abdominal discomfort (n = 113, 23.0 %). The majority of patients had either internal medicine (81.3 %) and/or neurologic (37.6 %) health problems. Conclusions Pain-associated diagnoses and the typical “unexplained” medical conditions (chronic fatigue syndrome, fibromyalgia, irritable bowel syndrome) are frequent among people contacting a center dedicated to undiagnosed diseases. The chief symptoms are mostly unspecific. An interdisciplinary organizational approach involving mainly internal medicine, neurology and psychiatry/psychosomatic care is needed.

Interferon-{beta} is an established treatment for patients with multiple sclerosis (MS) but its mechanisms of action are not well understood. Viral infections are a known trigger of MS relapses. Toll-like receptors (TLRs) are key components of the innate immune system, which sense conserved structures of viruses and other pathogens. Effects of interferon-{beta} on mRNA levels of all known human TLRs (TLR1-10) and the TLR adaptor molecule MyD88 were analyzed in peripheral blood mononuclear cells (PBMCs) of healthy donors by quantitative real-time PCR and by transcriptome analysis in PBMCs of 25 interferon-{beta}-treated patients with relapsing-remitting MS. Regulation of TLR protein expression by interferon-{beta} was investigated by flow cytometry of leukocyte subsets of healthy subjects and of untreated, interferon-{beta}-, or glatiramer acetate-treated patients with MS. Interferon-{beta} specifically upregulated mRNA expression of TLR3, TLR7, and MyD88 and downregulated TLR9 mRNA in PBMCs of healthy donors as well as in PBMCs of patients with MS. Plasmacytoid dendritic cells (pDCs) were identified as the major cell type responding to interferon-{beta} with increased expression of TLR7 and MyD88 protein. In line with this, expression of TLR7 protein was increased in pDCs of interferon-{beta}-treated, but not untreated or glatiramer acetate-treated patients with MS. Interferon-{beta}-induced upregulation of TLR7 in pDCs is of functional relevance since pre-treatment of PBMCs with interferon-{beta} resulted in a strongly increased production of interferon-{alpha} upon stimulation with the TLR7 agonist loxoribine. Flow cytometry confirmed pDCs as the cellular source of interferon-{alpha} production induced by activation of TLR7. Thus, upregulation of TLR7 in pDCs and a consequently increased activation of pDCs by TLR7 ligands represents a novel immunoregulatory mechanism of interferon-{beta}. We hypothesize that this mechanism could contribute to a reduction of virus-triggered relapses in patients with MS.