Increased serum neopterin levels in mycosis fungoides and Sézary syndrome

Sir, Pteridines represent pyrazino-(2,3-d)-pyrimidine compounds. Neopterin (6-d-erythro-trihydroprolypteridine) is a pyrazino-pyrimidine molecule synthesized by the macrophage, from guanosine triphosphate, stimulated by interferon-g. An increased neopterin level is a good reflection of the activation of cellular immunity. In several malignant diseases, elevated levels of neopterin in urine and serum have been observed. Serum neopterin concentration was measured by radioimmunoassay in patients with mycosis fungoides (MF) (n = 10; age = 48±86 years; six men, four women) and SeÂzary syndrome (n = 4; age = 28±72 years; three men, one woman). The diagnosis was made on clinical and histological criteria according to the classification of the European Organization for Research and Treatment of Cancer (EORTC). In this study three patients with MF were included with stage 1a (MF confined to the skin with , 10% surface area involved), one patient with stage 1b (MF confined to the skin with . 10% surface area involved), four patients with stage 1c (MF confined to the skin with skin tumours), two patients with erythrodermic MF and four patients with SeÂzary syndrome. All patients received treatment at the moment serum samples were taken for the determination of the neopterin concentration. They did not have any concomitant diseases nor had they received any other drugs. Sera from 10 untreated patients with mild (n = 2) to severe (n = 8) chronic plaque psoriasis (age = 29±70 years; six men, four women), 10 patients with untreated mild (n = 4) to severe (n = 6) atopic dermatitis (age = 25±65 years; three men, seven women) without any concomitant diseases, and 10 healthy volunteers without skin diseases were used as controls. Neopterin levels in the sera of patients and controls were determined using a commercially available radioimmunoassay kit (Henning, Berlin, Germany) which is highly specific with an analytical sensitivity of 0 ́1 ng/mL. The upper limit of the normal range is approximately 10 nmol/L serum (i.e. 2 ́5 ng/mL). The purpose of this study was to evaluate the serum neopterin concentration as an additional marker for disease activity in the primary cutaneous T-cell lymphomas, MF and SeÂzary syndrome. Serum neopterin levels of 10 patients with psoriasis vulgaris had a range of 3 ́8±6 ́8 nmol/L (mean 5 ́7 nmol/L) and in 10 patients with atopic dermatitis the serum neopterin concentration had a range of 2 ́9±9 ́9 nmol/L (mean 6 ́4 nmol/L). In 10 healthy volunteers the serum neopterin concentration had a range of 3 ́8±7 ́6 nmol/L (mean 5 ́4 nmol/L). In 10 patients with MF, the serum neopterin concentration had a range of 5 ́5±54 ́4 nmol/L (mean 16 ́3 nmol/L). The three patients with stage 1a and the one patient with stage 1b MF had serum neopterin concentrations below the upper limit of the normal range, ranging from 5 ́5 to 9 ́5 nmol/L. All four patients with stage 1c and the two patients with erythrodermic MF had serum neopterin values above the upper limit of the normal range, ranging from 13 ́5 to 54 ́4 nmol/L. One patient with stage 1c MF was followed during treatment with ultraviolet A radiation in combination with psoralens (PUVA). A serum sample was taken before therapy and 8 weeks later during therapy. There was clinical amelioration of the disease and the serum neopterin level dropped slightly from 17 ́0 nmol/L to 13 ́0 nmol/L. In four patients with the SeÂzary syndrome, the serum neopterin concentration had a range of 5 ́7±15 ́6 nmol/L (mean 9 ́5 nmol/L). There was a significant difference between MF in comparison with psoriasis vulgaris, atopic dermatitis and healthy controls (P , 0 ́01), but not between SeÂzary syndrome and psoriasis vulgaris, atopic dermatitis and healthy controls (P . 0 ́05). Serum neopterin levels in healthy controls were similar to those found in the literature. In the case of atopic dermatitis, the serum neopterin concentration was also below the upper limit of the normal range. This was previously investigated in vitro. Here the authors suggested that a possible dysregulation of interferon-g may be related to increased IgE and IgG4 production. In two studies, pretreatment serum neopterin concentrations were not elevated in psoriasis patients and there was no correlation between improvement or deterioration of the psoriasis area and severity index score and the serum neopterin levels. One study showed that fully oxidized urine neopterin levels were significantly elevated in a psoriatic group but not in patients with MF. In our study, we did not find serum neopterin levels above the upper limit of the normal range (, 10 nmol/L) in patients with mild to severe psoriasis. An explanation for this contradictory result could be that serum neopterin concentration was determined as opposed to urine neopterin, in our study. We found significantly elevated levels of serum neopterin in MF. This was due to high neopterin levels in stage 1c (n = 4) and erythroderma (n = 2) but not in stage 1a (n = 3) and 1b (n = 1) which demonstrates a correlation between the stage of the disease and the serum neopterin concentration. These results suggest that in the case of disseminated MF even higher serum neopterin concentrations could be expected. The reason why we did not find elevated neopterin levels in patients with SeÂzary syndrome, in contrast to the study mentioned above, could be due to the exclusion criteria; for example, the patients received ongoing chemotherapy before serum was taken for the determination of the neopterin concentration. We observed a minor decrease in the serum neopterin level with clinical amelioration of the disease in one patient with MF stage 1c after 8 weeks of treatment with PUVA therapy. High levels of serum neopterin in this study demonstrate the role of activated T lymphocytes in patients with MF and