The Clinical Retrospective Analysis Of Drug Induced Hypersensitivity Syndrome(DIHS)

IntroductionDrug induced hypersensitivity syndrome(DIHS) is also called Drug reaction with eosinophilia and systemic symptoms(DRESS).It has a delayed onset, usually 2–8 weeks after drug administration, and is characterized by fever, severe skin rashes, enlarged lymph nodes,haematological abnormalities and internal organ involvement.The most common culprit drug is antiepileptic drugs,sulfonamides and sulfones are also common.It has been estimated that the overall population risk is between 1 in 1000 and 1 in 10000 drug exposures, the mortality rate is 10%,potentially threaten life. ObjectiveThe present study we retrospectively scored the patients with drug induced hypersensitivity syndrome(DIHS) in recently 10 years using the Regi SCAR scoring system. We summarized clinical manifestations,laboratory examination and treatment outcome.Moreover, we corelated the culprit drugs, cutaneous manifestations and dermatopathological features with organ involvement in order to provide a guide for clinical diagnosis and prognosis assessment. MethodsWe collected the 23 cases that final diagnosis for DIHS in department of dermatology of Xijing Hospital between 2006 and 2014.We detailedly scored the 23 cases using the Regi SCAR scoring system and the 20 probable/definite DIHS were included in our present study. We summarized clinical manifestations,laboratory examination and treatment outcome of these cases. ResultsThe 23 patients that final diagnosis for DIHS were collected, of them 20 probable/definite DRESS defined by the Regi SCAR scoring system were screened.11 definite cases and 9 probable cases.12(60%) were male and 8(40%) were female, the males to females ratio was 1.5:1.The mean age of these patients was 43.0 years(range: 14–72 years),the mean latency period from the initiation of causative drug administration to the onset of symptoms was 18 days(range: 10–37 days).The during time was vary from mouths to years.The culprit drugs were carbamazepine(n=4,20%),sulfasalazine(n=4,20%), allopurinol(n=3,15%), lamotrigine(n=1,5%),other culprit drugs were azithromycin, cefaclor, meropenem, clindamycin, amoxicillin respectively(n=1,5%),3 another patients had more than two culprit drugs. All patients,8(40%) cases of causative drugs were antiepileptic drugs(AEDs), 12(60%) cases of causative drugs were n-AEDs. In our study, the latency periods of patients who taken AEDs were longer than those who taken n-AEDs(115d:95d,P=0.016).Liver injury was found in 18(90%) of patients, nine patients(5%) had kidney involvement,the heart can be affected in 6(30%) patients,the lung injury can be seen in 6(30%)patients.9(45%) patients had splenomegaly20 patients had various cutaneous manifestations. The most common dermatitis, seen in 13 out of 20 patients(65%), was a morbilliform erythema, 5(25%) patients presented with an exfoliative erythroderma,2(10%) patients had an eruption which was similar to atypical targets. Besides,1 patient had pustules. 5(25%) patients had prominent facial swelling. 5(25%) patients had oral mucosa involvement, 4 patient had lips erosion,1 patient oral mucosa was involved. Genitalia mucosa was injured in 1(5%) patient. No involvement of the mucosae of the eyes, nose were seen.The serum creatinine of patients with allopurinol was significantly higher than patients with other culprit drugs(126:84μmol/L,P=0.013).Skin biopsies were performed on 17 patients, made comparsions with 11 ER. Normal keratinization, parakeratosis, hyperkeratosis were seen both DIHS and ER, there is no statistical significance. The histopathological characteristics of lymphocytic extravasation(P=0.005),epidermal spongiosis(P=0.031) and interface vacuolization(P=0.008) were significantly more prominent in DIHS than ER. Dermal atypical lymphocytic infiltration in DIHS was significant(P=0.006). Necrotic keratinocytes, dermal papillary oedema perivascular lymphocytic infiltration; eosinophilic infiltration, extravasation of erythrocytes, perifollicular, peri-sweat gland, perisebaceous gland and peri-nerve lymphocytic infiltration were observed both DIHS and ER, but there is no statistical significance.All patients were treatment with methylprednisolone sodium succinate, and initial dose varied from 120mg/d to 500mg/d.Besides,3 patients were treated combined with intravenous immunoglobulin(IVIG).The patients who left hospital had oral corti costeroids.Our patients all had good recorvery and had no death. Conclusion1.The most common cause of drug-induced hypersensitivity syndrome is carbamazepine, followed by sulfasalazine, allopurinol, the cases induced by antibiotics are not rare.2.The cutaneous manifestations of drug-induced hypersensitivity syndrome are four patterns: a morbilliform erythema, an exfoliative erythroderma, a atypical targetoid erythema and a extensive erythema. A morbilliform erythema is the most common. In addititon, facial edema is a another character of drug-induced hypersensitivity syndrome. Mucosal involvement is also common.3. The patients with allopurinol are inclined to kidney injury.4.The histopathological feature of drug-induced hypersensitivity syndrome have more prominent lymphocytic extravasation(P=0.005),epidermal spongiosis(P=0.031) and interface vacuolization(P=0.008) compared with exanthematous reactions. Dermal atypical lymphocytic infiltration is another important histopathological characteristics. Besides, necrotic keratinocytes located in upper epidermis have auxiliary diagnosis significance.