| ObjectiveWith the social and economic development, common disease spectrum has changed enormously from the past. Related medication use has increased due to the higher incidence of gout and cardiovascular disease and cutaneous adverse drug reactions (CADRs) have occurred more frequently. Different causative drugs may cause drug eruptions with different clinical features. An update on the major causative drugs and their characteristics may help us diagnose CADRs and improve the treatment of drug eruption patients. This study will retrospectively analyze the characteristics of patients with CADRs including sensitizing drugs, latency period, types of eruptions and treatment. The objective of this research is to evaluate the associated agents and the types of drug eruptions in a hospital-based population over a 5-year period, and provide references for clinical medication choice and drug use safety.MethodsClinical records of 734 in-patients with both admitting diagnosis and discharging diagnosis of CADRs at the Department of Dermatology, Huashan Hospital affiliated to Fudan University from Jan 2004 to Dec 2008 were retrospectively studied. Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and exfoliative dermatitis (ED) were defined as severe CADRs (SCADRs). Other types of CADRs were defined as NS-CADRs, including morbiliform eruptions, erythema multiforme-like eruptions, urticaria, purpura and fixed drug eruption. The latency period of CADRs indicated the time between the intake of the agent and the onset of the symptoms. Maximum prednisone dosage (MPD) was defined as the maximum daily prednisone dosage administered when most of the original skin rash was resolving and no appearance of new rash was observed for at least 3 days. Total prednisone dosage (TPD) was defined as the total prednisone dosage administered to control the disease. With the retrospective analysis of the 734 clinical cases, this study will discuss the associated agents, types of eruptions, latency period, length of hospitalization and treatment.ResultsThe number of total CADRs in-patients has been increasing every year from 113 in 2004 to 216 in 2008, especially for the last two years of this study period (2007 & 2008). And we found that there was no substantial increase or decrease in the percentage of in-patients diagnosed with CADRs, which fluctuated between 10.73% and 13.29%. Among the CADRs patients, the percentage of patients with SCADRs remains relatively constant, varying between 10.85% and 18.58% during the 5 years. There were 625 cases of NS-CADRs and 109 cases of SCADRs. Of the 734 patients, 487 (66.3%) patients were female and 247 (33.7%) patients were male. Of NS-CADRs patients,193(30.9%) patients were male and 432(69.1%) patients were female (P=0.0001). Of the SCADRs patients,54 cases (49.5%) were male and 55(50.5%) patients were female (P=0.0001). The ratio of female to male for NS-CADRs patients was higher than that of SCADRs patients (P=0.0003). The age of the patients in the study was between 8 and 93 years (mean,43.87±17.37 years). The age of patients with NS-CADRs and SCADRs was between 8 and 87 years (mean, 43.1±16.6 years), and between 15 and 93 years (mean,48.4±20.7 years) respectively (P=0.0033). The mean age of SCADRs patients was remarkably higher than NS-CADRs (P=0.0031).Among all patients with CADRs,302 (41.14%) patients were confirmed with one medication intake history, the most frequently incriminated drugs being allopurinol, amoxicillin, cephalosporins, antiepileptic agents and antipyretic/analgesic agents. Among the NS-CADRs cases,250 had single drug use history and 375 had multiple drug use history. Among SCADRs cases,52 had single drug use history and 57 had multiple drug use history. The most common single associated drugs for NS-CADRs were amoxicillin (42 cases,16.80%), cephalosporins (41 cases,16.40%), antipyretic/analgesic agents (36 cases,14.40%) (mainly Carbamazepine) and allopurinol (31 cases,12.40%). As for SCADRs, the most frequent single associated agents were antiepileptic agents (20 cases,38.46%), allopurinol (18 cases,34.62%), antipyretic/analgesic agents (mainly acetaminophen) (4 cases,7.69%) and cephalosporins (3 cases,5.77%). According to different types of eruptions, there were 255 (34.74%) cases of erythema multiforme-like eruptions,192 (26.15%) of urticaria,159 (21.66%) of morbiliform eruptions,58 (7.90%) of Stevens-Johnson syndrome,29 (3.95%) of toxic epidermal necrolysis,22 (3.00%) of exfoliative dermatitis,10 (1.36%) of purpura and 9 (1.23%) of fixed drug eruption.Of all 734 cases,624 cases had their latency period clearly recorded, comprising of 545 NS-CADRs and 79 SCADRs. The mean latency period of the 624 patients was 7.64±8.32 days. For NS-CADRs patients, the mean latency was 6.9±7.7 days (P=0.0000). For SCADRs patients, the mean latency was 12.4±10.5 days (P=0.0000). The latency period of SCADRs was longer than NS-CADRs (P=0.0000). As regard to the most frequent associated agents, the latency period was 22.1±13.1 days for allopurinol,3.9±4.2 days for amoxicillin,5.1±4.5 days for cephalosporins,15.4±9.1 days for antiepileptics and 3.9±5.0 for antipyretic/analgesic agents. The latency of allopurinol was longer than other associated drugs (P=0.0000). The mean length of hospitalization was 8.68±6.84 days for all patients, 7.3±3.9 days for NS-CADRs and 16.6±12.4 for SCADRs (P=0.0000). The hospitalization time for SCADRs was longer than NS-CADRs (P=0.0000).The majority of the patients (90.05%) were treated with systemic corticosteroids and all of them recovered in this study. The maximum prednisone dosage (MPD) was 52.9±17.0mg/day for NS-CADRs and 76.8±23.6mg/day for SCADRs (P=0.0000). The MPD of SCADRs was higher than NS-CADRs (P=0.0000). The maximum total prednisone dosage (MTPD) was 373±216mg for NS-CADRs and 1003±630mg for SCADRs (P=0.0000). The MTPD of SCADRs was distinctly higher than NS-CADRs (P=0.0000).Among SCADRs patients, the MPD were 75.0±17.4mg/day for SJS,91.4±27.0mg/day for TEN and 61.1±23.3mg/day for ED, and the MPTD were 919±417mg for SJS,1416±850mg for TEN and 652±480mg for ED. The MPD of TEN was higher than SJS and ED, and the MPD of SJS was higher than ED (P=0.0000). The MTPD of TEN was higher than SJS and ED (P=0.0000). Combined with corticosteroid therapy, a dose of 0.4 g/kg/d of intravenous immunoglobulin (IVIG) for a mean period of 5 days was administered to 45 SACDRs patients, in whom corticosteroid therapy alone was not effective enough to control the eruptions. For the 734 CADRs patients,6 cases (0.01%) died, including 2 cases of SJS,3 cases of TEN and 1 case of ED. IVIG was administered to all 6 patients combined with corticosteroid therapy.Conclusions1. The most common associated agents were allopurinol, amoxicillin, cephalosporins, antiepileptic agents (mainly carbamazepine) and antipyretic/analgesic agents (mainly acetaminophen).2. Amoxicillin, cephalosporins, antipyretic/analgesic agents and allopurinol are the most frequent causative agents of NS-CADRs.3. Allopurinol and carbamazepine were the major associated drugs for SCADRs.4. Mortality rate decreased compared to previous reports.5. Prompt and proper adjustment of the dosage of corticosteroids and IVIG has played an important role in the successful outcome.
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