Biologics in Dermatology: An Integrated Review

The advent of biologics in dermatologic treatment armentarium has added refreshing dimensions, for it is a major breakthrough. Several agents are now available for use. It is therefore imperative to succinctly comprehend their pharmacokinetics for their apt use. A concerted endeavor has been made to delve on this subject. The major groups of biologics have been covered and include: Drugs acting against TNF-α, Alefacept, Ustekinumab, Rituximab, IVIG and Omalizumab. The relevant pharmacokinetic characteristics have been detailed. Their respective label (approved) and off-label (unapproved) indications have been defined, highlighting their dosage protocol, availability and mode of administration. The evidence level of each indication has also been discussed to apprise the clinician of their current and prospective uses. Individual anti-TNF drugs are not identical in their actions and often one is superior to the other in a particular disease. Hence, the section on anti-TNF agents mentions the literature on each drug separately, and not as a group. The limitations for their use have also been clearly brought out.     

Neonatal Purpura Fulminans Due to Methicillin Resistant Staphylococcus aureus

Abstract: Neonatal purpura fulminans is rare and may be inherited or acquired. It may ultimately lead to multiorgan failure and death. Purpura fulminans in a premature neonate resulting from Staphylococcus aureus septicemia is illustrated. Unfortunately, the baby succumbed to septicemia.     

Effects of pioglitazone and metformin on plasma adiponectin in newly detected type 2 diabetes mellitus

OBJECTIVE: This prospective study evaluates the effect of insulin sensitizers, pioglitazone (PGZ) and metformin (MET) on plasma adiponectin and leptin levels in subjects newly diagnosed with type 2 diabetes mellitus (T2DM). DESIGN: Double blind, randomized, active control, dose escalation study of 12 weeks treatment duration. PATIENTS: Thirty apparently healthy, treatment-naive T2DM patients diagnosed within the past 6 months. MEASUREMENTS: Plasma adiponectin and leptin levels were estimated by enzyme-linked immunosorbent assay (ELISA), and insulin resistance by the homeostasis model of assessment (HOMA-IR). RESULTS: Baseline plasma levels of adiponectin were lower in diabetic (n = 30) subjects than matched controls (n = 10, 6.6 +/- 1.1 vs 10.4 +/- 4.2 microg/ml, P = 0.021). The 12-week treatment with PGZ significantly increased adiponectin concentrations (6.6 +/- 1.1-17.9 +/- 7.4 microg/ml, P < 0.001) with no alteration in the MET treated group (6.8 +/- 1.5-6.7 +/- 2.8 microg/ml, P = 0.9). A significant decrease in plasma leptin levels was observed in the MET treated group (32.0 +/- 28.9-21.4 +/- 23.3 ng/ml, P = 0.024) but not in the PGZ treated group (23.9 +/- 24.1-22.4 +/- 25.4 ng/ml, P = 0.69). The alterations in plasma adiponectin and leptin levels were not associated with any change in body mass index (BMI). PGZ therapy improved insulin sensitivity to a greater degree (P = 0.007 and P = 0.001 for fasting plasma insulin (FPI) and HOMA-IR, respectively) than MET (P = 0.75 and P = 0.02 for FPI and HOMA-IR, respectively) but this improvement was not significantly different from that of MET at the end of 12 weeks (P = 0.146 and P = 0.09 for FPI and HOMA-IR, respectively). However, improvement in insulin sensitivity with PGZ was not commensurate with the increase in adiponectin. Better control of postbreakfast plasma glucose (PBPG) as well as decrease in serum triglycerides (TGs) were also seen with PGZ (PBPG, P < 0.001; TGs, P = 0.013). The rest of the parameters were comparable. Adverse reactions reported were minor and did not result in treatment discontinuation. CONCLUSIONS: Pioglitazone therapy appears to be better in achieving glycaemic control and increasing plasma adiponectin and insulin sensitivity in newly detected type 2 diabetics.     

The association of HIV/AIDS treatment side effects with health status, work productivity, and resource use

Due to stable incidence and improved survival rates, there are an increasing number of patients living with HIV/AIDS in the USA. Although highly effective, current antiretroviral therapies are associated with a variety of side effects. The role side effects play on health outcomes has not been fully examined. The current study assessed the association of medication side effects with (1) self-assessed health status; (2) work productivity and activity impairment; and (3) healthcare resource utilization. Data were from a cross-sectional patient-reported survey fielded in the USA using a dual methodology of Internet and paper questionnaires. A total of 953 patients living with HIV/AIDS who were currently taking a medication for their condition were included in the analyses. The most frequent side effects reported by patients were fatigue (70.72%), diarrhea (62.96%), insomnia (58.97%), dizziness (52.78%), neuropathy (52.68%), joint pain (52.36%), nausea (51.63%), and abdominal pain (50.37%). The presence of each side effect was associated with reduced self-assessed health status, increased productivity loss, increased activity impairment, and increased healthcare resource use. Controlling for CD4 cell counts in regression modeling did little to diminish the impact of side effects. Although not all side effects were associated with all outcomes, every side effect was associated with worse health status, some measure of increased work productivity loss, and/or some measure of increased healthcare resource use. Patients are living longer with HIV and, therefore, spending a greater length of time on treatment. The results of the current study suggest that many of these patients are experiencing a wide array of side effects from these therapies. These side effects have demonstrated a profound association with self-assessed health, work productivity, and healthcare resource use. Improved management of these side effects or development of treatments with a better side effect profile may have a substantial humanistic and economic benefit.     

Evaluation of analgesic efficacy,gastrotoxicity and nephrotoxicity of fixed-dose combinations of nonselective,preferential and selective cyclooxgenase inhibitors with paracetamol in rats

Nonsteroidal anti-inflammatory drugs (NSAIDs) are combined with paracetamol (PCM) with a view to enhance analgesic efficacy and reduce gastric toxicity. However, there are reports of enhanced nephrotoxicity with nonselective NSAID with PCM combinations. The present study investigated the analgesic efficacy, gastrotoxicity and nephrotoxicity of nonselective, preferential and selective cyclooxgenase inhibitors and their combination with PCM in rats.Graded doses of ibuprofen, meloxicam and celecoxib alone and their combination with fixed dose of PCM were administered to the rats by gavage for 14 days. The results showed that PCM potentiated the analgesic effect of all three classes of NSAIDs significantly as evidenced by increase in tail-flick latency in radiant heat method. Dose-dependent gastromucosal damage was produced by all the drugs, which was augmented significantly with PCM in the form of decreased total carbohydrate/protein ratio of mucin and increased gastric ulcer index. It was further confirmed by histopathology of rat’s stomach. The renal histopathology was conducted to evaluate inflammation, tubular damage, papillary necrosis, and interstitial changes. Increased nephrotoxicity was observed with all NSAIDs in dose-dependent manner and in combination with PCM.Our study revealed the augmented analgesia as well as enhanced gastrotoxicity and nephrotoxicity with all three major NSAIDs classes when combined with PCM. These findings highlighted the need for large pharmacoepidemiological studies to evaluate the magnitude of gastrotoxicity and nephrotoxicity in population who are on long-term treatment with NSAID combinations.     

Nail avulsion: indications and methods (surgical nail avulsion)

The nail is a subject of global importance for dermatologists, podiatrists and surgeons. Nail avulsion is a frequently undertaken, yet simple, intriguing procedure. It may either be surgical or chemical, using 40% urea. The former is most often undertaken using the distal approach. Nail avulsion may either be useful for diagnostic purposes like exploration of the nail bed, nail matrix and the nail folds and before contemplating a biopsy on the nail bed or for therapeutic purposes like onychocryptosis, warts, onychomycosis, chronic paronychia, nail tumors, matricectomy and retronychia. The procedure is carried out mostly under local anesthesia with or without epinephrine (1:2,00,000 dilution). Besides the above-mentioned indications, the contraindications and complications of nail avulsion are briefly outlined.     

Application of principal component analysis to study topography of hypoxic-ischemic brain injury

The regions at risk of ischemia following cardio-respiratory arrest have not been systematically analysed. This knowledge may be of use in determining the mechanism of ischemic injury at vulnerable sites. The aim of this study is to evaluate the use of principal component analysis to analyse the covariance patterns of hypoxic ischemic injury. The inclusion criteria were: age ≥ 17 years, cardio-respiratory arrest and coma on admission (2003-2011). Regions of ischemic injury were manually segmented on fluid attenuated inversion recovery (FLAIR) and diffusion weighted (DWI) sequences and linearly registered into common stereotaxic coordinate space. Topography of ischemic injury was assessed using principal component analysis (covariance data) and compared qualitatively against current method of topography analysis, the probabilistic method (frequency data). For the probabilistic data, subgroup analyses were performed using t-statistics while for the covariance data, subgroup analyses were performed by calculating the angle between the principle components. To account for bias due to a higher frequency of coma survivors in the studied group, we performed sensitivity analysis by sequentially removing coma survivors such that the final data set contained higher rate of death. Quantitative analysis between these methods could not be performed as they have different units of measurement. Forty one patients were included in this series (mean age ± SD=51.5 ± 18.9 years). In our probabilistic map, the highest frequency of ischemic injury on the DWI and FLAIR sequences was putamen (0.250), caudate (0.225), temporal lobes (0.175), occipital (0.150) and hippocampus (0.125). The first 6 principal components contained 77.7% of the variance of the data. The first component showed covariance between the deep grey matter nuclei and posterior cortical structures (contains 50.2% of the variance of the data). There was similarity in the findings of the subgroup analyses by the downtime whether it was assessed by t-statistics for probabilistic data or angle between the principal components for the covariance data. The sensitivity analysis showed that the pattern of ischemic injury did not change when the analysis was restricted to patients who died. In conclusion, PCA method has many advantages over probabilistic method. In the context of this dataset, PCA showed covariance between deep grey matter nuclei and the posterior cortical structures whereas the probabilistic map provided complementary information on the frequency of occurrence at these locations.