ABSTRACT
Background: Cutaneous adverse drug reactions (CADRs) may either be immunological or non-immunological. The precise mechanisms, however, are largely obscure. Other concomitant mechanisms may amplify and/or contribute to the severity and duration of a reaction. One such mechanism could be oxidative stress, a state of imbalance between reactive oxygen species, and their subsequent detoxification by antioxidants. Aims: (a) to assess the oxidative stress status in the blood of cutaneous drug reaction patients by assaying for reduced glutathione (GSH) and malondialdehyde (MDA) levels, (b) to determine the leukocyte migration inhibition (LMI) response in these patients in response to the suspected drug (s), and (c) to look for the association between oxidative stress parameters and LMI. Methods: Ethical committee approval was obtained for this study. Fresh venous blood samples were obtained from the patients of CADRs (group A) during the acute phase of reaction and healthy control subjects (group B). MDA levels, a measure of oxidative lipid damage, and reduced GSH levels, a measure of anti-oxidant capacity, were assayed in the blood samples of both groups using spectrophotometry. LMI response was measured by challenging the patients' peripheral blood mononuclear cells with the suspected drug to confirm immunological perturbation. Results: Totally 66 participants, 33 cases in group A and equal number of controls in group B, were studied. The mean MDA levels were found to be raised (P < 0.001), but GSH levels were significantly reduced in group A when compared with group B (P = <0.001). LMI response against drug(s) was performed in 33 cases (group A), out of which 25 cases showed a positive LMI response as follows: fixed drug eruption (10/25), SJS (5/25), urticaria (3/25), exfoliative dermatitis (2/25), morbilliform rash (2/25), erythroderma (1/25), vasculitis (1/25), and dapsone syndrome (1/25). The mean MDA levels were found to be significantly higher in the LMI positive CADRs (P < 0.001) when compared with LMI-negative ones, while no significant difference was seen for GSH (P = 0.100). Furthermore, there was a significant positive correlation between MDA levels and LMI response (r = 0.831, P < 0.001). On the other hand, a negative but statistically insignificant correlation was found between GSH and LMI response (r = -0.248, P = 0.271). Conclusion: CADR patients were found to be under oxidative stress based on MDA and GSH levels in the peripheral blood. There is a significant positive correlation of LMI response (against the causative drug) with MDA levels, which strongly associates oxidative stress with the immunopathogenesis in CADRs.
ABSTRACT
This study was undertaken to investigate the immunological mechanism of Behqet s syndrome, considered to be important in the pathogenesis of the disease. Seventy- three patients with complete, incomplete and suspected types of Behget's syndrotne were tested for leukocyte migration ingibition factor(LIF), one of the lymphokines. The results were as follows : 1. There was no difference between the average LIF activity of all the patients and that of eontrol. 2. LIF activity of complete type, according to Shirnizus classification, was significaritly lower than the control value. 3. LIF activity of ocular type, according to Lehners classification, was signficantly lower than the control value. 4. LIF activity for patients with 4 clinical symptoms was well below the value for patients with less symptomes 5. For patients with single clinical symptom, LIF activity of complete type was well below the values of incomplete and suspected types. 6. In suspected and mucocutaneous types, LIF activity was low when the patients showed two clinical symptoms than one. Thus, LIF activity was low for patients with complete, ocular and neurological types and with multiple symptorns.