A patient with bullous pemphigoid presenting with haemorrhagic oral erosions, oral haematoma and haemoptysis.

We present a case of a patient with bullous pemphigoid presenting with acquired haemophilia A. This is characterized by formation of antibodies or inhibitors against coagulation Factor VIII, leading to a prolonged activated partial thromboplastin time with normal prothrombin time and international normalized ratio. Our case emphasizes the need for increased awareness among dermatologists of this uncommon and potentially life-threatening condition. Click here for the corresponding questions to this CME article.

Systematic review of randomized controlled trials on interventions for melasma: an abridged Cochrane review.

BACKGROUND: Multiple treatments exist for melasma; they are often substandard and associated with side effects. OBJECTIVES: We sought to assess the effectiveness of interventions used in the management of all types of melasma. METHODS: We undertook a systematic review using the methodology of the Cochrane Collaboration. RESULTS: We included 20 studies with a total of 2125 participants covering 23 different treatments. A meta-analysis was not possible because of the heterogeneity of treatments. Triple-combination cream (hydroquinone, tretinoin, and fluocinolone acetonide) was more effective at lightening melasma than hydroquinone alone (relative risk 1.58, 95% confidence interval 1.26-1.97) or any of the agents in a dual-combination cream. Azelaic acid (20%) was significantly more effective than 2% hydroquinone (relative risk 1.25, 95% confidence interval 1.06-1.48) at lightening melasma. In 2 studies where tretinoin was compared with placebo, objective measures demonstrated significant reductions in the severity. However, only in 1 study did participants rate a significant improvement (relative risk 13, 95% confidence interval 1.88-89.74). LIMITATIONS: There was poor methodology, a lack of standardized outcome assessments, and short duration of studies. CONCLUSIONS: The current limited evidence supports the efficacy of multiple interventions. Randomized controlled trials on well-defined participants with long-term outcomes are needed.

Pulsed dye laser double-pass treatment of patients with resistant capillary malformations.

The pulsed dye laser is an effective and established treatment for port-wine stains and has become the generally accepted standard of care. However, in many cases, complete clearance cannot be achieved as a significant proportion of lesions become resistant to treatment. Multiple passes or pulse-stacking techniques have been used to improve the extent and rate of fading, but concerns over increased adverse effects have limited this clinical approach. In this work, a double-pass technique with the pulsed dye laser has been described, which may allow for increased depth of vascular injury, greater efficacy, and an acceptable risk profile. Our aim was to determine the efficacy and the rate of side-effects for a double-pass protocol with a pulsed dye laser (PDL) to treat patients previously treated with PDL and/or other laser modalities. A retrospective chart review was conducted of 26 patients treated with a minimum of three double-pass treatments alone, or in combination, with single pass conventional PDL. Almost half of the patients (n = 12) showed either a moderate or significant improvement in fading compared to pre-treatment photographs with the double-pass technique. In a further 12 patients, there was a mild improvement. In two patients, there was no change. Sixteen patients developed mild side-effects: blisters (n = 5), dry scabs (n = 11) and transient hyperpigmentation (n = 4). This preliminary experience suggests that a double-pass technique at defined intervals between the first and second treatment with PDL can further lighten some port-wine stains, which are resistant to conventional single-pass treatments. This technique may be a useful addition to the laser treatment of PWS and deserves further scrutiny with randomized prospective studies and histological analysis to confirm the increased depth of vascular injury.

Interventions for melasma.

BACKGROUND: Melasma is an acquired symmetrical pigmentary disorder where confluent grey-brown patches typically appear on the face. Available treatments for melasma are unsatisfactory. OBJECTIVES: To assess interventions used in the management of all types of melasma: epidermal, dermal, and mixed. SEARCH STRATEGY: In May 2010 we searched the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (Clinical Trials) in The Cochrane Library, MEDLINE, EMBASE, PsycINFO, and LILACS. Reference lists of articles and ongoing trials registries were also searched. SELECTION CRITERIA: Randomised controlled trials that evaluated topical and systemic interventions for melasma. DATA COLLECTION AND ANALYSIS: Study selection, assessment of methodological quality, data extraction, and analysis was carried out by two authors independently. MAIN RESULTS: We included 20 studies with a total of 2125 participants covering 23 different treatments. Statistical pooling of the data was not possible due to the heterogeneity of treatments. Each study involved a different set of interventions. They can be grouped into those including a bleaching agent such as hydroquinone, triple-combination creams (hydroquinone, tretinoin, and fluocinolone acetonide), and combination therapies (hydroquinone cream and glycolic acid peels), as well as less conventional therapies including rucinol, vitamin C iontophoresis, and skin-lightening complexes like Thiospot and Gigawhite.Triple-combination cream was significantly more effective at lightening melasma than hydroquinone alone (RR 1.58, 95% CI 1.26 to 1.97) or when compared to the dual combinations of tretinoin and hydroquinone (RR 2.75, 95% CI 1.59 to 4.74), tretinoin and fluocinolone acetonide (RR 14.00, 95% CI 4.43 to 44.25), or hydroquinone and fluocinolone acetonide (RR 10.50, 95% CI 3.85 to 28.60).Azelaic acid (20%) was significantly more effective than 2% hydroquinone (RR 1.25, 95% CI 1.06 to 1.48) at lightening melasma but not when compared to 4% hydroquinone (RR 1.11, 95% CI 0.94 to 1.32).In two studies where tretinoin was compared to placebo, participants rated their melasma as significantly improved in one (RR 13, 95% CI 1.88 to 89.74) but not the other. In both studies by other objective measures tretinoin treatment significantly reduced the severity of melasma.Thiospot was more effective than placebo (SMD -2.61, 95% CI -3.76 to -1.47).The adverse events most commonly reported were mild and transient such as skin irritation, itching, burning, and stinging. AUTHORS' CONCLUSIONS: The quality of studies evaluating melasma treatments was generally poor and available treatments inadequate. High-quality randomised controlled trials on well-defined participants with long-term outcomes to determine the duration of response are needed.

Patients with both basal and squamous cell carcinomas are at a lower risk of further basal cell carcinomas than patients with only a basal cell carcinoma.

BACKGROUND: The rate of development of further basal cell carcinoma (BCC) after first presentation is highly variable. The mechanisms that determine this phenotypic difference are unclear. OBJECTIVE: We assessed the risks of developing a subsequent BCC in patients who developed a BCC and a squamous cell carcinoma (SCC) and compared them with patients who developed a BCC only. METHODS: In all, 1040 patients who developed BCC only were compared with 140 patients who developed BCC and SCC to see whether the latter group included a high proportion of risk phenotypes (eg, male sex and fair skin). We then compared the number of BCCs developing per year in the two groups (174 BCC only and 71 BCC/SCC) during a 5-year period after initial BCC presentation. RESULTS: The BCC/SCC group demonstrated a significantly lower BCC/year rate than BCC only group. The rate of development of further BCC during 5-year follow-up was lower in the BCC/SCC group because a smaller number of patients developed subsequent BCC and not because the same proportion of patients developed lesions but in smaller numbers. After 5 years of follow-up, 51.1% of BCC and 74.6% of BCC/SCC cases were free from a subsequent BCC. Logistic regression analysis corrected for age at initial presentation confirmed that patients with BCC/SCC were less likely to develop a further BCC during the 5 years after initial presentation (P = .001, odds ratio = 0.31, 95% confidence interval 0.15-0.63). LIMITATIONS: Because of the large patient group and long study follow-up from the date of the index BCC or SCC, not all data were obtained. Where this is the case, the number of patients for whom the information is available is provided. CONCLUSIONS: Patients who develop a BCC are similar to patients who develop both a BCC and SCC, confirming the overlap of causative factors. Patients who develop both a BCC and SCC are less likely to develop BCCs compared with patients who develop BCC only.

The value of skin biopsy in inflammatory dermatoses.

The skin biopsy is considered one of the most important tools in dermatology. Two primary reasons a clinician may perform a skin biopsy are either to establish a diagnosis or to evaluate therapy. The objective of this study was to critically assess the value of the skin biopsy as a diagnostic test for inflammatory dermatoses. One hundred consecutive skin biopsy specimens where an inflammatory dermatosis was queried were reviewed. To assess the diagnostic ability of the skin biopsy, the frequency with which a correct diagnosis was made based on histopathological analysis alone was recorded, that is, an initial "blind" diagnosis made without clinical data. Once this was recorded, the clinical history was provided and a posthistory diagnosis reached. The posthistory diagnosis was then compared with the final working diagnosis in the patient case notes. In 55% of cases, histology was able to provide a prehistory specific diagnosis. In 31% of cases, histology was not able to provide a specific diagnosis but could provide a differential diagnosis. In two thirds of these (20 of the 31 cases), the diagnosis was reached posthistory with clinicopathologic correlation. In 12% of cases, histology could only provide a pattern analysis, and in 2% of cases, only a descriptive report could be issued. In 13% of cases, the biopsy provided the final working diagnosis, which had not been considered clinically. The skin biopsy for inflammatory dermatoses is clearly a worthwhile investigative procedure. Prehistory blind histology based on microscopic data provided an accurate diagnosis correlating to the working diagnosis in 53% of cases. The diagnostic boundaries of dermatopathology are such that in an additional 25 cases (25%) a diagnosis was reached with aid of clinical data proving the importance of providing a well-thought-out differential diagnosis. Overall, in 78% of cases, histology with the aid of clinical information was able to provide an accurate diagnosis correlating to the working diagnosis.

Adenovirus type 5 interactions with human blood cells may compromise systemic delivery.

Intravenous delivery of adenovirus vectors requires that the virus is not inactivated in the bloodstream. Serum neutralizing activity is well documented, but we show here that type 5 adenovirus also interacts with human blood cells. Over 90% of a typical virus dose binds to human (but not murine) erythrocytes ex vivo, and samples from a patient administered adenovirus in a clinical trial showed that over 98% of viral DNA in the blood was cell associated. In contrast, nearly all viral genomes in the murine bloodstream are free in the plasma. Adenovirus bound to human blood cells fails to infect A549 lung carcinoma cells, although dilution to below 1.7 x 10(7) blood cells/ml relieves this inhibition. Addition of blood cells can prevent infection by adenovirus that has been prebound to A549 cells. Adenovirus also associates with human neutrophils and monocytes ex vivo, particularly in the presence of autologous plasma, giving dose-dependent transgene expression in CD14-positive monocytes. Finally, although plasma with a high neutralizing titer (defined on A549 cells) inhibits monocyte infection, weakly neutralizing plasma can actually enhance monocyte transduction. This may increase antigen presentation following intravenous injection, while blood cell binding may both decrease access of the virus to extravascular targets and inhibit infection of cells to which the virus does gain access.

Virus-directed enzyme prodrug therapy: intratumoral administration of a replication-deficient adenovirus encoding nitroreductase to patients with resectable liver cancer.

PURPOSE: Virus-directed enzyme prodrug therapy depends on selective delivery of virus encoding a prodrug-activating enzyme to tumor, followed by systemic treatment with prodrug to achieve high levels of the activated cytotoxic at the intended site of action. The use of the bacterial enzyme nitroreductase to activate CB1954 (5-(aziridin-1-yl)-2,4-dinitrobenzamide) to a short lived, highly toxic DNA cross-linking agent has been demonstrated in tumor xenografts. In this study, we report the first clinical trial investigating the feasibility, safety, and transgene expression of a replication-defective adenovirus encoding nitroreductase (CTL102) in patients with liver tumors. PATIENTS AND METHODS: Patients with resectable primary or secondary (colorectal) liver cancer received a single dose of CTL102 delivered by direct intratumoral inoculation 3 to 8 days before surgical resection. RESULTS: Eighteen patients were treated with escalating doses of CTL102 (range, 10(8)-5 x 10(11) virus particles). The vector was well tolerated with minimal side effects, had a short half-life in the circulation, and stimulated a robust antibody response. Dose-related increases in tumoral nitroreductase expression measured by immunohistochemical analysis have been observed. CONCLUSION: Direct intratumoral inoculation of CTL102 to patients with primary and secondary liver cancer is feasible and well tolerated. The high level of nitroreductase expression observed at 1 to 5 x 10(11) virus particles mandates further studies in patients with inoperable tumors who will receive CTL102 and CB1954.

Heart failure in a multiethnic population in Kuala Lumpur, Malaysia.

BACKGROUND: There are established differences in cardiovascular disease in different racial groups. Worldwide, the literature regarding the clinical epidemiology of congestive heart failure (CHF) in non-white populations is scarce. OBJECTIVES: To document the prevalence of CHF in the multiracial population of Malaysia, and to describe the clinical features and management of these patients. SETTING: Busy city centre general hospital in Kuala Lumpur, Malaysia. RESULTS: Of 1435 acute medical admissions to Kuala Lumpur General Hospital over the 4-week study period, 97 patients (6.7%) were admitted with the primary diagnosis of CHF. Coronary artery disease was the main aetiology of CHF, accounting for almost half (49.5%) the patients, followed by hypertension (18.6%). However, there were variations in associated aetiological factors between ethnic groups, with diabetes mellitus affecting the majority of Indians-as well as underutilisation of standard drugs for CHF, such as the angiotensin converting enzyme (ACE) inhibitors, which were only used in 43.3%. CONCLUSION: Amongst acute medical admissions to a single centre in Malaysia the prevalence of CHF was 6.7%. Coronary artery disease was the major aetiological factor in heart failure accounting for almost half the admissions. The under-prescription of ACE inhibitors was similar to other clinical surveys carried out amongst Caucasian populations in the West.