Rare diseases: why is a rapid referral to an expert center so important?

BACKGROUND: Patients with rare diseases usually go through years of diagnostic odysseys. The large number of rare diseases and the associated lack of expertise pose a major challenge to physicians. There are few physicians dealing with patients with rare diseases and they usually work in a limited number of specialized centers. The aim of this study was to evaluate the diagnostic efficiency of an expert center. METHODS: The diagnostic pathway of 78 patients of the outpatient clinic for rare inflammatory systemic diseases with renal involvement was analyzed retrospectively. For this purpose, each examination day was documented with the corresponding examinations performed from the onset of initial symptoms. Three time points were considered: The time when patients first visited a physician with symptoms, the time when patients consulted an expert, and the time when they received the correct diagnosis. In addition, it was documented whether the diagnosis could be made without the expert, or only with the help of the expert. The examinations that confirmed the diagnosis were also documented for each patient. RESULTS: A correct diagnosis was made without the help of the expert in only 21% of cases. Each patient visited an average of 6 physicians before consulting the expert. Targeted diagnostics enabled the expert to make the correct diagnosis with an average of seven visits, or one inpatient stay. However, referral to the expert took an average of 4 years. CONCLUSION: The data show that rapid and targeted diagnostics were possible in the expert center due to the available expertise and the interdisciplinary exchange. Early diagnosis is of great importance for many patients, as an early and correct therapy can be decisive for the course of the disease.

Health economic benefits through the use of diagnostic support systems and expert knowledge.

BACKGROUND: Rare diseases are difficult to diagnose. Due to their rarity, heterogeneity, and variability, rare diseases often result not only in extensive diagnostic tests and imaging studies, but also in unnecessary repetitions of examinations, which places a greater overall burden on the healthcare system. Diagnostic decision support systems (DDSS) optimized by rare disease experts and used early by primary care physicians and specialists are able to significantly shorten diagnostic processes. The objective of this study was to evaluate reductions in diagnostic costs incurred in rare disease cases brought about by rapid referral to an expert and diagnostic decision support systems. METHODS: Retrospectively, diagnostic costs from disease onset to diagnosis were analyzed in 78 patient cases from the outpatient clinic for rare inflammatory systemic diseases at Hannover Medical School. From the onset of the first symptoms, all diagnostic measures related to the disease were taken from the patient files and documented for each day. The basis for the health economic calculations was the Einheitlicher Bewertungsmaßstab (EBM) used in Germany for statutory health insurance, which assigns a fixed flat rate to the various medical services. For 76 cases we also calculated the cost savings that would have been achieved by the diagnosis support system Ada DX applied by an expert. RESULTS: The expert was able to achieve significant savings for patients with long courses of disease. On average, the expert needed only 27 % of the total costs incurred in the individual treatment odysseys to make the correct diagnosis. The expert also needed significantly less time and avoided unnecessary examination repetitions. If a DDSS had been applied early in the 76 cases studied, only 51-68 % of the total costs would have incurred and the diagnosis would have been made earlier. Earlier diagnosis would have significantly reduced costs. CONCLUSION: The study showed that significant savings in the diagnostic process of rare diseases can be achieved through rapid referral to an expert and the use of DDSS. Faster diagnosis not only achieves savings, but also enables the right therapy and thus an increase in the quality of life for patients.

Glucocorticoid Effects on Tissue Residing Immune Cells in Giant Cell Arteritis: Importance of GM-CSF.

Giant cell arteritis (GCA) is a systemic granulomatous vasculitis clinically characterized by a prompt response to glucocorticoid therapy. Dendritic cells (DCs) play a central role in the pathogenesis of the disease and are increased in temporal arteries from GCA patients. The aim of this study was to determine the effects of glucocorticoid therapy on granulomatous infiltrates and on peripheral DCs of GCA patients. Immunohistochemical staining of temporal artery specimens from 41 GCA patients revealed a rapid reduction of the number of DCs after initiation of glucocorticoid treatment. TUNEL staining was performed to quantify apoptotic S100+ DC, CD3+ T cells, and CD68+ macrophages in the granulomatous infiltrates. An increase of apoptotic cells up to 9 ± 2% after 4-5 days of glucocorticoid therapy and up to 27 ± 5% (p < 0.001, compared to earlier timepoints) after 6-10 days was detected. A decrease of CCL19 and CCL21 expression was observed after starting glucocorticoid therapy. Granulocyte-macrophage colony-stimulating factor (GM-CSF) expression also significantly decreased under glucocorticoid therapy. No GM-CSF expression was detected in the control specimens. Glucocorticoid therapy leads to a rapid, time-dependent reduction of DCs in temporal arteries from GCA patients and reduction of mediators for cell migration. Our data suggest GM-CSF as a novel therapeutic target of GCA.