Dietary supplement product composed of natural ingredients as a suspected cause of erythema multiforme: A case report and identification for the confident false positivity of lymphocyte transformation test.

Growing and sustainable consumption of health-care products raises a controversial issue underlying the reliability of an in vitro diagnostic approach for adverse skin reaction. This report aimed to: (i) discuss the causative nature of a commercial dietary supplement composed of natural ingredients, particularly an Euglena-containing product, suspicious for erythema multiforme in our exemplified case; and (ii) to address the assay suitability of the lymphocyte transformation test (LTT) for identifying allergic reaction to any ingredient(s) of the product. A Japanese elderly man developed erythema multiforme after intake of a commercially available natural dietary product, whose LTT was positive. His clinical course and positive LTT suggested a provisional diagnosis of natural dietary product-induced eruption. We conducted an inquiry survey for the standard LTT with any commercial products containing Euglena in three major Japanese laboratory services and identified 22 subjects, almost all of whom (21/22, 95.6%) showed a positive LTT for any Euglena-containing products as a suspected causative. Seven normal healthy volunteers who had no intake history of Euglena-containing products showed an equivalent LTT positivity rate with the same product taken by our case; culprit components of the product included Euglena, Angelica keiskei, Barley grass and Chlorella. A cell-free culture system and enzyme-linked immunoassay suggest that the high LTT positivity relies on the non-specific lymphoproliferative activity, and not contamination of uncharacterized microorganisms and endotoxins. Because of the constitutive false positivity of LTT, this assay is unreliable for in vitro supportive diagnosis of adverse skin events caused by dietary products containing particular natural ingredients, as well as herbal materials.

Serum interleukin-6 level is a useful marker in evaluating therapeutic effects of levamisole and Chinese medicinal herbs on patients with oral lichen planus.

BACKGROUND: Oral lichen planus (OLP) is a T cell-mediated inflammatory disease. Interleukin-6 (IL-6) is a pro-inflammatory cytokine that has effects on cellular and humoral immunities. Previous studies have shown that keratinocytes and tissue-infiltrating mononuclear cells from OLP lesions can secrete IL-6. In some OLP patients, the high serum IL-6 levels are reduced after treatment, suggesting that IL-6 may be a useful marker in evaluating therapeutic effects and in monitoring the disease status of OLP. METHODS: In this study, we used a solid phase, two-site sequential chemiluminescent immunometric assay to determine the baseline serum levels of IL-6 in a group of 180 patients with erosive OLP (EOLP), nonerosive OLP (NEOLP), erythema multiforme (EM), traumatic ulcers (TU), oral submucous fibrosis (OSF), pemphigus vulgaris (PV), or Sjögren's syndrome (SS), and in 77 normal control subjects. Some OLP patients were treated with levamisole plus Chinese medicinal herbs or levamisole only for 0.5-5.5 months and their serum IL-6 levels were measured after treatment. RESULTS: We found that approximately 99% of the normal control subjects and the patients with EM, TU, or OSF had a normal serum IL-6 level less than 5.0 pg/ml. However, 15% (22/149) OLP patients, 15% (20/136) EOLP patients, 20% (5/25) major type EOLP patients, 14% (15/111) minor type EOLP patients, 15% (2/13) NEOLP patients, 14% (1/7) EM patients, 43% (3/7) PV patients, and 100% (6/6) SS patients had a serum IL-6 level greater than 5.0 pg/ml. The mean serum IL-6 level in patients with OLP (3.4 +/- 3.1 pg/ml, P < 0.001), EOLP (3.4 +/- 3.2 pg/ml, P < 0.001), major type EOLP (4.9 +/- 3.5 pg/ml, P < 0.001), minor type EOLP (3.0 +/- 3.0 pg/ml, P < 0.01), or NEOLP (4.2 +/- 1.5 pg/ml, P < 0.001) was significantly higher than that in normal control subjects (2.0 +/- 1.5 pg/ml). A significant difference in the mean serum IL-6 level was also found between major type and minor type EOLP patients (P < 0.01). The mean reduction of serum IL-6 level in OLP patients treated with levamisole plus Chinese medicinal herbs was significantly higher (7.4 +/- 4.7 pg/ml) than that in OLP patients treated with levamisole only (3.8 +/- 2.3 pg/ml, P < 0.05), suggesting that the combination therapy was superior to levamisole only. CONCLUSION: We conclude that levamisole and levamisole plus Chinese medicinal herbs can modulate the serum IL-6 level in OLP patients. IL-6 may be a useful marker in evaluating therapeutic effects and in monitoring the disease status of OLP.