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clinmed/2003010001v1 (January 27, 2003)
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New Treatments Emerge as Sarcoidosis Yields Up its Secrets

Background: Sarcoidosis is a hyper-inflammatory disorder of uncertain etiology. The objective of this study was to identify patients who were reporting hypersensitivities to sunlight, and investigate whether this trait might help to identify the etiology of sarcoid inflammation. Results: After studying patients who were able to control their Sarcoidosis symptoms simply by limiting their exposure to sunlight, and others who were benefiting from Angiotensin Receptor Blockade, we identified, and confirmed, a working hypothesis detailing each step of the molecular chemistry leading to the inflammation seen in Sarcoidosis. The study also identified, and validated, a number of novel treatments. Discussion: We found that the secosteroid hormone 1,25-dihydroxyvitamin D (1,25-D) clearly plays an important part in the etiology and symptomology of Sarcoidosis, regardless of the calcemic state of the patient. We described an inflammatory biochemistry which identified 1,25-D and Angiotensin II as the key hormonal mediators. Many patients’ symptoms were eased when the concentration of the metabolite 25-hydroxyvitamin D (25-D) was reduced by isolation from sunlight, and the removal of all sources of Vitamin D from the diet. 25-D provides fuel for the unregulated extra-renal production of the secosteroid. This novel therapy also improved markers of disease activity, such as Angiotensin Converting Enzyme, and Alkaline Phosphatase, at the same time that the 1,25-D levels were being normalized. The D-Ratio, serum 1,25-D (pg/ml) divided by 25-D (ng/ml), gives an indication of the amount of nonrenal 1,25-D being produced within the granulomatous inflammation. It can be used to monitor a patient’s response to therapy. Angiotensin II plays a vital role in the inflammatory cycle, and a novel form of Angiotensin Receptor Blockade was confirmed as a probable therapeutic alternative to the use of systemic corticosteroids.

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