HX35 The spleen-did history of the Kveim–Siltzbach test

Abstract The diagnosis of sarcoidosis is reliant on manifestation of typical lesions in one or more organs and the exclusion of other conditions known to cause granulomatous disease. Granulomatous lesions may not be readily accessible for biopsy. As a result, diagnosis can be prolonged because many other diagnoses can share similar clinical presentations, histopathological features, imaging findings and blood results. However, in 1941 Morten Ansgar Kveim from Danbolt’s department of dermatology in Oslo reported intradermal injection of heat-sterilized, sarcoid-positive lymph node tissue. This resulted in the development of a granulomatous nodule within 9 days to 4 weeks, in 12 of 13 patients with sarcoidosis. The lesions were biopsied and the presence of a noncaseating granuloma was considered a positive Kveim reaction. No reactions occurred in control individuals. Nickerson also reported nonspecific skin reactions secondary to the intradermal injection of skin sarcoid tissue. However, histology of the reactions was not reported (James DG, Williams WJ. Kveim–Siltzbach test revisited. Sarcoidosis 1991; 8: 6–9). These results were confirmed by several other physicians. In 1954, Louis Siltzbach, an American physician, embarked on a larger-scale clinical trial that involved intradermally injecting splenic tissue into the volar aspect of the forearm. The Kveim–Siltzbach (KS) test was popularized and utilized as a diagnostic test, with a sensitivity of 76.4% and specificity of 72.8% (Rogers FJ, Haserick JR. Value of Kveim test as a diagnostic measure in sarcoidosis; a preliminary report. Cleve Clin Q 1954; 21: 79–89). Despite highly promising trial results, the validity and safety of the test have been challenged. The reliability of the test is contingent upon selecting the correct reagent for the test. Standardizing the potency of the reagent is difficult. The KS test had been in use for approximately 50 years. It was considered a simple, safe and accurate test, until risks of infection transmission became more prevalent. Further issues concerning storage and availability of the reagent also rendered the test unpopular (James and Williams). A further perceived disadvantage of the KS test is the delay in obtaining a result due to the tedious course of granuloma formation. However, the current practice of extensive diagnostic elimination can also be time consuming, often leading to inconclusive results. Sarcoidosis remains a challenging diagnosis. The KS test has well-known historical roots for its unique nature and high-yield result. However, it has faced a degree of criticism over time. Despite this, the technique has potential to provide opportunities to develop more robust investigations specific to sarcoidosis.