Oxidative stress and leukocyte migration inhibition response in cutaneous adverse drug reactions.

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.

Chronic idiopathic urticaria: comparison of clinical features with positive autologous serum skin test.

BACKGROUND: Chronic idiopathic urticaria (CIU), in its extremely severe form, can pose a therapeutic challenge to the treating physician. It has been noted that in one third of such patients, autoantibodies against the IgE receptor are seen and such patients have more severe and unremitting urticaria. AIM: To compare clinical features of autoimmune urticaria with those of other CIU patients. METHODS: We conducted a prospective study in an attempt to correlate the clinical features with autoantibodies, indirectly detected via the autologous serum skin test (ASST), which is the simplest and the best in vivo clinical test for detection of basophil histamine-releasing activity. DISCUSSION: Out of 100 patients with chronic idiopathic urticaria, 34 showed a positive reaction to the autologous serum skin test and it was found that the frequency and severity of attacks was higher in these patients. CONCLUSION: ASST may be used as a simple and cost-effective test for the classification of chronic urticaria, which has proven to be a therapeutic challenge to the treating physician.

Autologous serum therapy in chronic urticaria: old wine in a new bottle.

BACKGROUND: Chronic urticaria (CU) is one of the most challenging and frustrating therapeutic problems faced by a dermatologist. A recent demonstration of abnormal type 1 reactions to intradermal autologous serum injections in some CU patients has led to the characterization of a new subgroup of "autoimmune chronic urticaria". This has rekindled interest in the age-old practice of autologous blood injections as a theoretically sound treatment option in these patients. AIMS: To evaluate the efficacy of repeated autologous serum injections (ASIs) in patients with recalcitrant chronic urticaria. METHODS: A cohort of 62 (32 females) CU patients with a positive autologous serum skin test (ASST) (group 1) was prospectively analyzed for the efficacy of nine consecutive weekly autologous serum injections with a postintervention follow-up of 12 weeks. Another group of 13 (seven females) CU patients with negative ASST (group 2) was also treated similarly. In both groups, six separate parameters of disease severity and activity were recorded. RESULTS: Demographic and disease variables were comparable in both groups. The mean duration of disease was 1.9 +/- 0.3 years (range = 3 months to 32 years) in group 1 and 1.5 +/- 0.2 years (range = 3 months to 10 years) in group 2. In the ASST (+) group, 35.5% patients were completely asymptomatic at the end of the follow-up while an additional 24.2% were markedly improved. In the ASST (-) group, these figures were 23 and 23% respectively. The intergroup difference for complete subsidence was statistically significant (P < 0.05). In both groups, the most marked reduction was seen in pruritus and antihistamine use scores followed by the size and frequency of the wheals. CONCLUSION: Autologous serum therapy is effective in a significant proportion of ASST (+) patients with CU. A smaller but still substantial number of ASST (-) patients also benefited from this treatment.