Drug-Induced Bullous Disorders Publications (702)
Drug-Induced Bullous Disorders Publications
Antinuclear antibody, perinuclear and cytoplasmic antineutrophil cytoplasmic antibody were found negative. Punch biopsy from skin of the upper trunk revealed dense neutrophilic infiltration of dermis without signs of vasculitis, suggestive of Sweet's syndrome. In view of the temporal association with azathioprine and absence of an obvious alternative aetiology, provisional diagnosis of drug-induced bullous Sweet's syndrome was made. Azathioprine was discontinued and high-dose oral prednisolone initiated. The response was dramatic with resolution of skin lesions within 72 h without further recurrence at fourth week of follow-up.
Local examination revealed that the right ostium of the maxillary sinus was open and that the maxillary sinus mucosa was invaded by tumor. Biopsy revealed a histopathological diagnosis of squamous cell carcinoma. We therefore diagnosed the patient as a case of maxillary sinus carcinoma (T3N0M0) based on the CT, MRI and FDG-PET findings. During chemoradiotherapy for maxillary sinus cancer, the patient developed oral mucosal inflammation of progressively worsening severity; we initially thought that the symptom was a side effect of the treatment; however, several days later, skin lesions appeared throughout the body. We consulted a dermatologist, who suspected SJS. The patient was initiated on high-dose steroid therapy (steroid pulse therapy), and the symptoms improved. Because of SJS is a fatal drug eruption, early diagnosis and prompt treatment are important. In patients receiving chemoradiotherapy showing severe oral mucosal inflammation outside the irradiation area or oral mucosal inflammation associated with skin lesions throughout the body, it is necessary to bear in mind the possibility of SJS.
Currently, treatment of aphthous ulcers is palliative and symptomatic. Topical treatments (topical anesthetics, topical steroids and sucralfate) are the first line therapy. Recurrent aphthous stomatitis (RAS) is defined by the recurrence of oral aphthous ulcers at least 4 times per year. RAS is often idiopathic but can be associated with gastro-intestinal diseases (i.e. celiac disease, inflammatory bowel diseases), nutritional deficiencies (iron, folates...), immune disorders (HIV infection, neutropenia) and rare syndromes. Behçet's disease is a chronic, inflammatory, disease whose main clinical feature is recurrent bipolar aphthosis. Colchicine associated with topical treatments constitutes a suitable treatment of most RAS. Thalidomide is the most effective treatment of RAS but its use is limited by frequent adverse effects. Oral ulcers can be related to a wide range of conditions that constitute the differential diagnoses of aphthous ulcers. Oral ulcers are classified into three main groups: acute ulcers with abrupt onset and short duration, recurrent ulcers (mainly due to postherpetic erythema multiforme) and chronic ulcers (with slow onset and insidious progression). Acute oral ulcers are due to trauma, bacterial infections (including acute necrotizing ulcerative gingivitis), deep fungal infection, gastro-intestinal (namely inflammatory bowel disease) or systemic diseases. Chronic oral ulcers may be drug-induced, or due to benign or malignant tumors. Every oral solitary chronic ulcer should be biopsied to rule out squamous cell carcinoma. A solitary palatal ulcer can be related with necrotizing sialometaplasia.
pneumoniae-induced SJS. He responded well to antibiotics and steroids initially, but went on to develop pseudomembranous conjunctivitis requiring bilateral amniotic membrane grafting. SJS is most commonly drug-induced, however, M. pneumoniae is the commonest infectious cause and should be considered in the differential diagnosis. It is also important to get specialist care involved early to minimise the long-term effects of any complications.
We enrolled 5802 subjects who had results of HLA typing test from August 2005 to July 2014. Total 28 SJS/TEN patients were categorized based on culprit drugs (allopurinol, lamotrigine, carbamazepine) and identified the presence of HLA-B*58:01, HLA-B*44:03, HLA-B*15:02, and HLA-A*31:01.
HLA-A*24:02 (20.5%), HLA-B*44:03 (10.0%), and HLA-Cw*01:02 (17.1%) were the most frequent type in HLA-A, -B, and -C genes, respectively. Allele frequencies of HLA-B*58:01, HLA-B*44:03, HLA-A*31:01, and HLA-B*15:02 were 7.0%, 10.0%, 5.0%, and 0.3%, respectively. In 958 allopurinol users, 9 subjects (0.9%) were diagnosed with SJS/TEN. Among them, 8 subjects possessed HLA-B*58:01 allele. SJS/TEN induced by allopurinol was more frequently developed in subjects with HLA-B*58:01 than in subjects without it [odds ratio: 57.4; confidence interval (CI) 7.12-463.50; p<0.001]. Allopurinol treatment, based on screening by HLA-B*58:01 genotyping, could be more cost-effective than that not based on screening. HLA-B*44:03 may be associated with lamotrigine-induced SJS/TEN (odds ratio: 12.75; CI 1.03-157.14; p=0.053). Among carbamazepine users, only two patients experienced SJS/TEN and possessed neither HLA-B*15:02 nor HLA-A*31:03.
HLA gene frequencies varied in Korea. Screening of HLA-B*58:01 before the use of allopurinol might be needed to anticipate probability of SJS/TEN.
In fact, the identification of new specific genetic markers involved in the response to drugs, will be of great utility to establish a more personalized therapeutic approach and to prevent the appearance of these adverse reactions. In this review, we summarize recent progresses in the Pharmacogenetics studies related to Stevens-Johnson syndrome/toxic epidermal necrolysis reporting the major genetic factors identified in the last years as associated with the disease and highlighting the use of some of these genomic variants in the clinical practice.