Spectrum of cutaneous adverse reactions to aromatic antiepileptic drugs and human leukocyte antigen genotypes in Thai patients and meta-analysis

Aromatic antiepileptic drugs (AEDs)-induced cutaneous adverse drug reactions (cADRs) add up to the limited use of the AEDs in the treatment and prevention of seizures. Human leukocyte antigen-B (HLA-B) alleles have been linked to AEDs-induced cADRs. We investigated the association between cADRs (including Stevens–Johnson syndrome; SJS/toxic epidermal necrolysis; TEN, drug reaction with eosinophilia and systemic symptoms; DRESS, and Maculopapular eruption; MPE) caused by AEDs (phenytoin, carbamazepine, lamotrigine, phenobarbital and oxcarbazepine) and HLA-B alleles in Thai population. Through the case-control study, 166 patients with AEDs-induced cADRs, 426 AEDs-tolerant patients (AEDs-tolerant controls), and 470 healthy subjects (Thai population) were collected. The HLA genotypes were detected using the polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSOP) method. We also performed a meta-analysis with these data and other populations. The carrier rate of HLA-B*15:02 was significantly different between AEDs-induced cADRs group and AEDs-tolerant group (Odds ratio; OR 4.28, 95% Confidence interval; CI 2.64–6.95, p < 0.001), AEDs-induced cADRs group and Thai population (OR 2.15, 95%CI 1.41–3.29, p < 0.001). In meta-analysis showed the strong association HLA-B*15:02 with AEDs-induced cADRs (OR 4.77, 95%CI 1.79–12.73, p < 0.001). Furthermore, HLA-B*15:02 was associated with SJS/TEN induced by AEDs (OR 10.28, 95%CI 6.50–16.28, p < 0.001) Phenytoin (OR 4.12, 95%CI 1.77–9.59, p = 0.001) and carbamazepine (OR 137.69, 95%CI 50.97–371.98, p < 0.001). This study demonstrated that genetic association for AEDs-induced cADRs was phenotype-specific. A strong association between HLA-B*15:02 and AEDs-induced SJS/TEN was demonstrated with an OR of 10.79 (95%CI 5.50–21.16, p < 0.001) when compared with AEDs-tolerant group. On the other hand, the carrier rates of HLA-B*08:01, HLA-B*13:01, and HLA-B*56:02 were significantly higher in the DRESS group compared with the AEDs-tolerant group (p = 0.029, 0.007, and 0.017, respectively). The HLA-B*15:02 allele may represent a risk factor for AEDs-induced cADRs.

Clinico-pathological features of the drug reaction with eosinophilia and systemic Symptoms syndrome: A case study

Drug reaction with eosinophilia and systemic symptoms syndrome is a syndrome with a varied spectrum of clinical features. The cutaneous manifestations can be an urticarial, maculopapular eruption also including, vesicles, bullae, pustules, purpura, target lesions, facial edema, cheilitis, and erythroderma. Systemic manifestations include lymphadenopathy, fever, and leukocytosis (often with eosinophilia or atypical lymphocytosis), as well as hepatitis, nephritis, pneumonitis, myositis, and gastroenteritis, in descending order. Diagnosis can be made on the basis of the clinical picture and the RegiSCAR (Registry of Severe Cutaneous Adverse Reaction group) scoring system. Here, we present the case of a 40-year-old male with a history of herbal medicine intake after which he developed a diffuse skin rash.

“CLINICO-PATHOLOGICAL STUDY OF SURGICAL LESIONS OF FILARIASIS”

Background: Lymphatic lariasis, transmitted by mosquitoes is the commonest cause of lymphedema in endemic countries. Among 120 million infected people in 83 countries, up to 16 million have lymphedema. Microlariae ingested by mosquitoes grow into infective larvae. These larvae entering humans after infected mosquito bites grow in the lymphatics to adult worms that cause damage to lymphatics resulting in dilatation of lymph vessels. This earliest pathology is demonstrated in adults as well as in children, by ultrasonography, lymphoscintigraphy and histopathology studies. Once established, this damage was thought to be irreversible. This lymphatic damage predisposes to bacterial infection that causes recurrent acute attacks of dermato-lymphangio-adenitis in the affected limbs. Bacteria, mainly streptococci gain entry into the lymphatics through 'entry lesions' in skin, like interdigital fungal infections, injuries, eczema or similar causes that disrupt integrity of skin. Methods-This study was conducted among 124 patients who attended SOPD and Filaria clinic (103) and admitted in Surgical wards (21) of S.G.M Hospital Rewa. All incidence, surgical manifestations and clinical diagnosed of lariasis in surgical patients include the study. Children with <6 years of age, critically ill patients and cases where calcication has been established for the exclusion criteria. Follow up of the patients was done on 7th, 14th and 21th day and the treatment effects were recorded every time. Complications, progression / regression and over all effects were recorded. Results- Filarial disease was diagnosed in 124 patients. The majority of the patients with Filarial disease 28.22% and Microlaria positive 80% were in the age group of 21-30 years . Youngest patient was 7 years male with right thigh lymphedema and oldest patient was 74 years old male with bilateral hydrocele. male : female ratio with Filarial disease is 2.86:1. Regional lymphadenopathy was noted in 17.74%, overlying skin was inamed and oedematous in 12.9%, hypertrophic or thick skin 4.03%, ulceration and nodularity was present in 2.41% each .Maculopapular eruption and blisters was present in 1.61 % cases each. The commonest manifestation constituted 54.03% of cases. Epididymoorchitis was present in 25%, lymphangitis in 13.71%, lymphadenitis in 11.29%, hydrocele in 7.26%, and cellulitis in 4.84% cases. Funiculitis and elephantiasis in 4.84% and 4.03% respectively. Conclusion- Reducing the suffering caused by LF through morbidity management and disability prevention. The general population should be well educated and informed about the disease and prevention from mosquito bite. Patients who are already suffering from the disease should be made aware of the treatment modalities available and benets of promoting self-hygiene and self-help regimens. From the current study we can conclude that prevalence of laria in Vindhya Region is 0.11% which is less than 1% which was target under NPELF.

The Contradiction of Drug Allergy in Patients with Cystic Fibrosis and Review of the Literature

Background: Cystic fibrosis (CF) is reported to be a risk factor for drug hypersensitivity. However, there is conflicting data about true prevalence of drug allergy in children with CF. Methods: The suspicious drug hypersensitivity reactions (DHR) of children with CF were enquired by European Network for Drug Allergy (ENDA) questionnaire and skin tests and/or drug provocation tests were performed according to established guidelines. Results: Two hundred and nineteen children (48.9% boys; median [IQR] age, 8.4 years [4.8-12.4 years]) with cystic fibrosis were included in the study, from whom 22 patients with 24 suspected DHRs were evaluated. Most of the suspected DHRs were non-immediate (n=16, 66.6%) type and the offending drugs were amoxicillin clavulanic acid (n=7), macrolides (n=4), trimethoprim sulfamethoxazole (TMP/SMX) (n=2), piperacillin tazobactam (n=1), pancrelipase (n=1) and ursodeoxycholic acid (n=1). Eight (33.3%) of the DHRs were classified as immediate [ceftriaxone (n=2), ceftazidim (n=2), meropenem (n=1), ambisome (n=2), vancomycin (n=1)]. The main presenting clinical presentations were maculopapular eruption (41.6%) and urticaria (37.5%), accompanied by angioedema (8.3%), flushing (12.5%) and vomiting (8.3%). Nine skin tests (with beta-lactam protocol in 6 patients) and 24 DPTs were performed and none of the skin tests revealed a positive result, however 2 DPTs with TMP/SMX were positive. Conclusion: Actual drug allergy was demonstrated in 2 of 219 patients (0.9%) with nonbeta-lactam antibiotics. These results conflict with previous researches that showed higher drug allergy rates but were consistent with some recent studies. Numerous and long-term use of multiple drugs during management of cystic fibrosis may contribute to tolerance development.

Pseudomembranous conjunctivitis with hand, foot and mouth disease in a pregnant woman : a case report

Background Hand, foot, and mouth disease (HFMD) is a common systemic infection that is caused by an enterovirus, normally Coxsackie A16. Generally, it affects children or immunocompromised adults. Only a few reports have described pseudomembranous conjunctivitis associated with HFMD. We aim to describe the clinical outcomes and ocular findings of a 37-year-old female with HFMD and concurrent severe pseudomembranous conjunctivitis, who was 28 weeks pregnant. Case presentation A female patient who was 28-weeks pregnant was referred for an ophthalmological review due to pain and injection in both eyes. The patient was hospitalized under obstetrics and gynecology and evaluated for Behcet’s disease with oral and perineal ulcers. In an ophthalmic examination, both eyes were observed to have a conjunctival injection. Behcet’s disease-associated conjunctivitis was diagnosed. Topical steroids and antibiotics were administered every 6 h. Two days after her presentation, a maculopapular eruption occurred on her palms. Enterovirus type 71 was detected in a serum virus antibody test, and the patient was diagnosed with HFMD. After 7 days, severe pseudomembranous conjunctivitis and corneal epithelial defects occurred in both eyes. Topical steroids were administered every 3 h, and the pseudomembrane was removed every 2 to 3 days. The pseudomembrane did not occur after 3 weeks, but corneal erosion persisted. After 3 months, the corneal erosion had completely resolved. Conclusions HFMD-associated conjunctivitis is a rare complication in adults, however it can appear as a severe pseudomembranous conjunctivitis. In this case, the removal of the pseudomembrane and topical steroids helped improve the symptoms.

Systemic reaction during intradermal skin tests with beta-lactams

Beta-lactam (BL) antibiotics are the most frequent cause of drug hypersensitivity in children, inducing both immediate and non-immediate reactions. Here we report a case of a 4-year-old child with a disseminated maculopapular exanthema 7 days after the first dose of amoxicillin–clavulanate, referred to our paediatric allergy department. Skin prick tests were negative. Intradermal tests were performed and, after 10 hours, indurated wheals larger than 10×10 mm with progressive erythema and disseminated maculopapular eruption were developed, related to amoxicillin and amoxicillin–clavulanate. Systemic reactions to BL skin tests are rarely reported and the majority are immediate reactions. This case illustrates a rare example of a non-immediate systemic reaction to intradermal tests, underlying the importance of skin testing before drug provocation tests in cases of moderate to severe non-immediate reactions.