Adverse reactions and tolerability of high-dose sublingual allergen immunotherapy.

BACKGROUND: Sublingual allergen immunotherapy is an effective treatment against allergic respiratory disease. Many studies have shown the safety of this type of therapy, although the factors that might affect the tolerability of high-dose sublingual immunotherapy have not been well established. The aim of this study was to determine the factors that affect the tolerability of sublingual allergen immunotherapy. PATIENTS AND METHODS: A total of 183 subjects aged ≥5 years, diagnosed with allergic rhinitis with/without mild to moderate asthma due to sensitization to grass, olive pollen, or mites, were included in this open, retrospective, multicentric, noninterventional study. Sublingual immunotherapy was administered for at least 3 months. RESULTS: The most frequent adverse reaction was oral pruritus (13.7% of the patients). Most of the reactions were local (84.7%) and immediate (93.5%) and occurred during the initiation phase (60.6%). All reactions were mild to moderate in severity. No serious adverse reactions were registered. When comparing factors with potential influence on the occurrence of adverse reactions, the results between the groups of subjects with and without adverse reactions showed no statistically significant differences in sex (P=0.6417), age (P=0.1801), years since the disease was first diagnosed (P=0.3800), treatment composition (P=0.6946), polysensitization (P=0.1730), or clinical diagnosis (P=0.3354). However, it was found that treatment duration had a statistically significant influence (3 months, >3 months: P=0.0442) and the presence of asthma was close to statistical significance (P=0.0847). CONCLUSION: In our study, treatment duration is significantly associated with the occurrence of adverse reactions after the administration of high doses of sublingual allergen immunotherapy.

Involvement of CCL27-CCR10 interactions in drug-induced cutaneous reactions.

BACKGROUND: Drug-induced skin reactions, including toxic epidermal necrolysis and Stevens-Johnson syndrome, are severe bullous cutaneous diseases of uncertain etiology, although cytotoxic T cells seem to be involved. Cutaneous T cell-attracting chemokine (CTACK/CCL27) is selectively expressed in skin and attracts CCR10-expressing cells. Exclusive CTACK expression by keratinocytes suggests its involvement in inflammatory skin diseases. OBJECTIVE: We addressed whether CTACK/CCL27 production by the epidermis and CCR10+ lymphocytes are involved in toxic epidermal necrolysis and Stevens-Johnson syndrome. METHODS: We measured CTACK expression by epidermal cells in 2 patients with drug-induced bullous skin reactions and compared it to lesional skin from several drug-induced exanthemas. In parallel we measured CCR10 mRNA in peripheral blood mononuclear cells from the patients during the course of the disease and in lymphocytes infiltrating the skin. RESULTS: CTACK expression levels in skin biopsies from the 2 patients with drug-induced bullous reactions were higher than those found in healthy subjects or in other drug-induced exanthemas. CCR10 mRNA levels were also elevated in peripheral blood lymphocytes and in lesional skin during the acute phase of the disease. Moreover, resolution was associated with a return to baseline of both CTACK and CCR10 receptor expression. CONCLUSION: CTACK-CCR10 interactions may be involved in the selective recruitment to the skin of cytotoxic lymphocytes in toxic epidermal necrolysis and Stevens-Johnson syndrome, as well as in less severe drug-induced cutaneous diseases.

Delayed reactions to drugs show levels of perforin, granzyme B, and Fas-L to be related to disease severity.

BACKGROUND: Drugs can induce different immunologic reactions; T-cell mediated responses produce the most severe reactions. Although in vitro studies show that T cells recognize drugs or their metabolites and induce an effector cytotoxic response, direct in vivo evidence of involvement is lacking. T lymphocytes produce cytotoxic markers that are responsible for 2 major pathways to cell death: granule-mediated exocytosis (perforin and granzyme B) and Fas/FasL interaction. OBJECTIVE: The purpose of this investigation was to establish the role of proinflammatory TNF-alpha and cytotoxic markers in subjects with delayed responses to drugs. METHODS: We assessed expression levels by quantitative-competitive PCR of TNF-alpha, perforin, granzyme B, and FasL in mononuclear cells from peripheral blood and blister fluid from subjects with delayed reactions to drugs. Samples were obtained within 24 hours of the reaction and 30 days later. Fifteen patients were included and classified according to severity of the reaction, as follows: (A) maculopapular exanthema, (B) desquamative exanthema, (C) Stevens-Johnson syndrome, (D) toxic epidermal necrolysis. RESULTS: At the acute stage, there was a large increase in TNF-alpha (9-fold), perforin (6-fold), and GrB (7-fold) in patients in comparison with control subjects. FasL was expressed in PBMCs only in Stevens-Johnson syndrome and toxic epidermal necrolysis. A high association between cytotoxic markers and disease severity was seen (P <.001). CONCLUSION: our data show that TNF-alpha, perforin, GrB, and FasL are increased in the early stage of disease, suggesting that a cytotoxic mechanism might be taking part. These findings support the role of T cells in allergic drug reactions and provide further clues pertaining to therapeutic interventions.