A rare cutaneous tumour.

A clinicopathological correlation case of a rare cutaneous tumour, which demonstrated a very rare recurrence with uncertainty remaining over the long-term prognosis for the patient. Click https://www.wileyhealthlearning.com/#/online-courses/a975ab43-2d48-46fb-8dba-7df9792fd778 for the corresponding questions to this CME article.

Sporadic pemphigus foliaceus and class II human leucocyte antigen allele associations in the white British and Indo-Asian populations in the UK.

BACKGROUND: Pemphigus foliaceus (PF) has both genetic and environmental susceptibility factors. Current data on human leucocyte antigen (HLA) in patients with sporadic PF are limited. AIM: To better define the distribution of HLA alleles in patients with PF in the UK. METHODS: We recruited 36 patients [26 of white British (WB) descent, 10 of Indo-Asian (IA) descent] with PF who were living in the UK and 159 ethnically matched normal controls, and analysed their class II HLA DRB1 and DQB1 allele distribution. RESULTS: There was an increased frequency of DRB1*1404 in association with DQB1*0503 in IA patients with PF. The DRB1*04 allele group as a whole had an increased frequency (P < 0.001) in the WB patient group compared with controls. The alleles contributing to this significance were DRB1*0401 (P = 0.03) and DRB1*0404 (P < 0.01). CONCLUSION: This is the largest HLA association study in sporadic PF from the UK to date. There appears to be a difference in PF susceptibility alleles between WB and IA patients, highlighting the importance of racial variation in genetic susceptibility to disease development.

Regional nerve blockade prior to direct injection to achieve anaesthesia of the nasal ala.

BACKGROUND: Dermatological surgical procedures involving the nasal alae are commonplace in clinical practice. Direct infiltration of local anaesthetic into the nasal ala is extremely uncomfortable. OBJECTIVES: In this prospective clinical study, we investigate the effectiveness of alar anaesthesia provided by an infraorbital nerve block (IOB). METHODS: We recruited 100 consecutive patients requiring dermatological surgical procedures involving the nasal ala (or other sites necessitating an IOB). Following topical mucosal anaesthesia, an IOB was administered via the intraoral route. Effectiveness of anaesthesia was assessed after 10 min by testing the perception of a sharp stimulus at five standardized reference points on the nasal ala. If the ala was not completely anaesthetized, blockade of the external nasal branch of the anterior ethmoidal nerve (external nerve block, ENB) was performed. Sensation of the nasal ala was re-assessed after 10 min using the above method. RESULTS: Complete anaesthesia of the nasal ala was achieved with an IOB in 66 of 100 (66%) patients. Of the remaining 34 patients, the addition of an ENB achieved complete anaesthesia in 15 (44%). CONCLUSIONS: An IOB provides effective alar anaesthesia in the majority of patients. In those where it is ineffective for complete anaesthesia, an ENB is a useful adjunct. We recommend using an IOB (and ENB if required) prior to direct infiltration of local anaesthetic into the nasal ala to reduce patient discomfort.

Acute generalized exanthematous pustulosis associated with azathioprine hypersensitivity.

Acute generalized exanthematous pustulosis (AGEP) is identified by several characteristic features. We present a patient showing AGEP associated with azathioprine hypersensitivity. To our knowledge, this is the first reported case of this association.

Evidence of an association between desmoglein 3 haplotypes and pemphigus vulgaris.

BACKGROUND: Pemphigus vulgaris (PV, OMIM 169610) is a severe blistering disorder of the skin and mucous membranes, caused by the production of autoantibodies directed against the epithelial adhesive protein desmoglein 3. Although an association between PV and HLA class II alleles has been established, the genetic factors predisposing to the disease remain poorly understood, the rarity of PV hampering the recruitment of substantial patient cohorts. OBJECTIVES: To investigate DSG3 as a candidate PV susceptibility gene. METHODS: We examined five DSG3 single nucleotide polymorphisms (rs8085532, rs3911655, rs3848485, rs3794925 and rs1466379) in two case-control datasets respectively originating from the U.K. (62 PV patients, 154 controls) and northern India (28 patients, 98 controls). RESULTS: In the U.K. sample, we observed a significant association between PV and the DSG3*TCCTC haplotype (Fisher's exact test P = 0.002). A related haplotype (DSG3*TCCCC) was associated with PV in the Indian dataset (P = 0.002). We also found that all British and Indian patients bearing DSG3 risk haplotypes carried at least one copy of a PV-associated HLA allele. CONCLUSIONS: These results suggest that genetic variation of DSG3 may be an additive risk factor predisposing to PV and warrant further investigations of this gene.

Toxic epidermal necrolysis: current evidence, practical management and future directions.

Toxic epidermal necrolysis (TEN) is a rare disorder characterized by extensive epidermal death. Almost all cases appear to be caused by an idiosyncratic drug reaction. Proposed pathogenic mechanisms are conflicting, and the evidence for the benefits of individual treatments is inadequate, and in some cases contradictory. The mortality rate remains high. We review the literature pertaining to the pathogenesis of TEN and drug reactions in general. The rationale for therapeutic interventions, together with reported evidence of efficacy, are considered. We present a composite model of TEN, based on previous work and suggested pathogeneses of TEN, mechanisms of drug reactions and reported cytotoxic lymphocyte (CTL) cytolytic pathways. In this system, TEN, like some other cutaneous drug eruptions, is an HLA class I-restricted, specific drug sensitivity, resulting in clonal expansion of CD8+ CTLs. Cytotoxicity is mediated by CTL granzyme and possibly death receptor (DR) ligand (DR-L), probably Fas ligand (FasL). Particular to TEN, there is then an amplification sequence involving further DR-L expression. FasL is likely to be particularly important but tumour necrosis factor (TNF) may well contribute, via the TNF receptor 1 (TNF-R1) death pathway. Alternatively, we suggest the possibility of upregulation of an antiapoptotic TNF-R1-nuclear factor kappaB pathway, which would proscribe treatments which downregulate this pathway. None of the published data on individual treatment efficacies is sufficiently strong to suggest a definitive single treatment. Currently a multifaceted regimen appears indicated, targeting various likely intermediary mechanisms, including elimination of residual drug, immunosuppression, inhibition of DR pathways, general antiapoptotic strategies, and aggressive supportive care. Particular attention has been directed at avoiding potential conflicts between different treatments and avoiding agents that theoretically might have a net proapoptotic rather than antiapoptotic effect. Nursing on a specialized unit is of paramount importance.