Proton pump inhibitor induced subacute cutaneous lupus erythematosus: Clinical characteristics and outcomes.

BACKGROUND: There is a growing literature reporting the association between proton pump inhibitor (PPI) use and subacute cutaneous lupus erythematosus (SCLE). AIMS: To compare the clinical characteristics of a cohort of patients with PPI-induced SCLE, their clinical course and treatment with a control group of primary SCLE patients not exposed to PPI. METHODS: We conducted a matched case-control study in a tertiary referral setting at the Louise Coote Lupus Unit. There were 64 SCLE patients: 36 with PPI-induced SCLE and 28 patients with primary SCLE. RESULTS: Twenty-six patients (72%) had pre-existing SLE in the PPI-induced SCLE group. Lower limb skin lesions were significantly more prevalent in the PPI group (p < 0.0001). The prevalence of anti-Ro and anti-Ro-52 antibodies was numerically higher in the PPI group (64% and 60%), respectively, compared with 46% and 42% in the primary SCLE group. Peripheral blood eosinophils were normal in all patients in the PPI group. Thirteen patients underwent skin biopsy in the PPI group and 12 had histology in keeping with SCLE. The median time to presentation was 8 months with a median resolution period of 6 weeks. PPIs were stopped in 34 patients, while 2 patients continued treatment for other clinical indications. Twelve patients received concurrent oral corticosteroids. Two patients had severe SCLE in the form of Toxic Epidermal Necrolysis requiring critical care admission and were managed with corticosteroids, IV immunoglobulin and/or belimumab. CONCLUSION: Lower limb involvement is a pointer to PPI-induced SCLE which is likely a class effect with all PPI.

Unusually high α-proton acidity of prolyl residues in cyclic peptides.

The acidity of the α-proton in peptides has an essential role in numerous biochemical reactions and underpins their stereochemical integrity, which is critical to their biological function. We report a detailed kinetic and computational study of the acidity of the α-proton in two cyclic peptide systems: diketopiperazine (DKP) and triketopiperazine (TKP). The kinetic acidity (protofugality) of the α-protons were determined though hydrogen deuterium exchange studies in aqueous solutions. The acidities of the α-proton in prolyl residues were increased by 3-89 fold relative to other amino acid residues (prolyl > glycyl ≫ alanyl > tyrosyl). Experimental and computational evidence for the stereoelectronic origins of this enhanced prolyl reactivity is presented. TKPs were 106-fold more reactive than their DKP analogues towards deprotonation, which we attribute to the advanced development of aromaticity in the earlier transition state for proton transfer in these cases. A Brønsted linear free energy analysis of the reaction data was conducted to provide estimates of α-proton pK as.

A randomised half body prospective study of low and medium dose regimens using the 308 nm excimer laser in the treatment of localised psoriasis.

This study compared two dose-escalation regimens using the 308 nm excimer laser treating localised plaque psoriasis, to determine the optimal regimen. A randomised, left-right body trial was designed including patients aged >18 years with localised plaque psoriasis (<10% body surface area). The standard/low dose regimen started at 70% of the minimal erythema dose (MED), with 20% dose increments. The medium dose regimen commenced at 200% MED, with 25% increments. Patients were treated until disease clearance or a maximum of 36 treatments. Fifteen patients aged 28-55 years completed the study. Psoriasis severity index scores analysed at weeks 0, 6 and 12 showed a significant reduction with each regimen (p < 0.0001). Six patients cleared, seven had significant improvement with uneven clearance of plaques and two failed. Average remission was four months (range 1-12 months). There was a significant reduction in DLQI (p = 0.014). Excimer laser improved psoriasis and reduced DLQI scores, but clearance was incomplete for many patients and remission was short-lived. Adverse effects of pain and blistering were commoner with the medium dose regimen, without any benefit in psoriasis clearance.

The use of transient elastography and FibroTest for monitoring hepatotoxicity in patients receiving methotrexate for psoriasis.

IMPORTANCE: There is a need for noninvasive tools to monitor hepatotoxicity in patients with psoriasis who are receiving methotrexate sodium. OBJECTIVE: To evaluate the use of transient elastography (TE) and FibroTest (FibroSURE in the United States), an indirect serum marker of fibrosis, in this population. DESIGN, SETTING, AND PARTICIPANTS: Patients receiving methotrexate therapy for psoriasis between January 2008 and September 2009 were recruited from a dermatology outpatient department. Transient elastography and FibroTest were performed, and patients with abnormal results were considered for liver biopsy. Serial procollagen III peptide (PIIINP) results were recorded. INTERVENTIONS: Transient elastography uses pulse-echo ultrasonography to measure liver stiffness, and this result is an indirect measure of hepatic fibrosis. FibroTest is an indirect serum marker of hepatic fibrosis. MAIN OUTCOMES AND MEASURES: Procollagen III peptide, TE, and FibroTest results, as well as the need for liver biopsy in this cohort. RESULTS: Seventy-seven patients (41 male [53%]) were included. Fifty (65%) patients had a valid TE assessment, and 9 (18%) had an abnormal result (range, 7.1-11.3 kPa). Being overweight or obese increased the possibility of obtaining an invalid TE result significantly (P = .01). On univariate analysis body mass index (r = 0.40, P = .005) and age (r = 0.52, P = .005) were correlated with abnormal TE results. Seventy-one patients received a FibroTest and 11 of 70 analyzed (16%) had an abnormal result (METAVIR score >F1). Age (r = 0.31, P = .009), cumulative methotrexate dose (r = 0.31, P = .01), and duration of methotrexate therapy (r = 0.36, P = .002) were correlated with abnormal FibroTest results. There was no correlation between PIIINP levels and TE results or between PIIINP levels and FibroTest results. Steatosis was demonstrated in all 5 patients who received liver biopsies during the study. Two patients had hepatic fibrosis, with 1 showing a sinusoidal pattern of fibrosis attributed to steatohepatitis. CONCLUSIONS AND RELEVANCE: Transient elastography and FibroTest are effective noninvasive tools for monitoring hepatotoxicity in patients receiving methotrexate for psoriasis. We propose that the need for liver biopsy could be reduced if abnormalities in at least 2 tests (serial PIIINP, TE, or FibroTest) are required before biopsy is considered. This strategy should be evaluated in prospective studies.

The relevance of 7-day patch test reading.

BACKGROUND: Patch test readings are usually performed on day 2 (48 hours) and day 4 (96 hours). However, reports in the literature identify delayed allergy to metals, corticosteroids, antibiotics, some preservatives, acrylic and methacrylic monomers and p-phenylenediamine. OBJECTIVES: The aim of our study was to identify the benefit of performing a day 7 (168 hours) reading to identify relevant late positive reactions. PATIENTS/METHODS/MATERIALS: Two hundred three consecutive patients were patch tested to the British Society for Cutaneous Allergy standard series with additional test series selected according to clinical history and applied at the same time. RESULTS: Twenty-six patients (12.8%) had new positive reactions on day 7 (168 hours), with 28 relevant positive reactions to 21 allergens. These included mercury 0.5% (2/26); cobalt chloride 1% (2/26); colophony 20% (2/26); disperse blue mix 106/124 1% (2/26); preservatives (4/26) that included Methylchloroisothiazolinone/methylisothiazolinone, sodium metabisulfite, and diazolidinyl urea; fragrances (7/26); and gentamycin sulfate 20% (1/26). CONCLUSIONS: These results confirm findings in the literature and support the argument for performing a day 7 reading (168 hours) to identify relevant late positive reactions.

Methylchloroisothiazolinone and methylisothiazolinone allergic contact dermatitis and the effect of patch test concentration.

BACKGROUND: The isothiazolinones methylchloroisothiazolinone and methylisothiazolinone (MCI/MI) are the active ingredients in a frequently used preservative in cosmetic, household, and industrial products. OBJECTIVES: This study reviewed our department's cases of allergic contact dermatitis caused by MCI/MI, outlining their clinical presentation and possible sources of sensitization. The effect of changing the concentration of MCI/MI from 0.01% to 0.02% in the British Society for Cutaneous Allergy baseline series was also measured. METHODS: A total of 964 patients were patch tested to the British Society for Cutaneous Allergy baseline series in our department over 4 years. Patients were tested either to 0.01% MCI/MI (697) or 0.02% MCI/MI (267). RESULTS: Twenty-one patients (2.2%) had positive reactions to MCI/MI. Of patients tested to 0.02% MCI/MI, 3.8% had a positive reaction compared with 1.6% of those tested to MCI/MI 0.01%. Ten patients (48%) had perianal dermatitis; of these, 50% had used moist toilet wipes. CONCLUSIONS: We highlight MCI/MI as important contact allergens found in moist toilet wipes and should be considered particularly in patients with facial, hand, and perianal allergic contact dermatitis. Patch testing to 0.01% MCI/MI may underestimate its allergenic potential, missing more than half of allergic cases compared with testing to 0.02%. To identify isothiazolinone allergy, we recommend that 0.02% MCI/MI should be used in baseline series.

Assessment of biological activity of novel peptide analogues of angiotensin IV.

OBJECTIVES: Angiotensin IV (Ang IV) is a metabolite of angiotensin II which acts on specific AT(4) receptors identified as the enzyme insulin regulated aminopeptidase (IRAP). The transduction process of these receptors is unresolved, but Ang IV inhibits the aminopeptidase activity. Ang IV improves cognition in animal models thus there is a desire to develop metabolically stable analogues for further development. METHODS: Peptide analogues of Ang IV were obtained commercially or synthesised. Each peptide was tested in vitro for its ability to inhibit the aminopeptidase activity (IRAP) of mouse brain homogenates and for its effects on isolated rat uterine smooth muscle. KEY FINDINGS: [Des-Val(1) ]-Ang IV, acetylated-Ang IV-amide, Ang IV-amide and [des-His(4) ]-Ang IV all inhibited IRAP. [Sar(1) , Ile(8) ]-Angiotensin II (10 µm) had an effect greater than that of Ang IV or any of the other analogues studied. In isolated uterine smooth muscle, angiotensins II and IV induced contractions, which could be antagonised by an AT(1) -receptor antagonist. None of the novel peptides induced uterine smooth muscle contractions, but [Sar(1) , des Arg(2) -Gly(8) ]-angiotensin II showed significant antagonism of the contractile effects of angiotensin II and carboxyamide-terminated Ang IV-NH(2) showed antagonism of Ang IV-induced contractions. CONCLUSIONS: This study provides five novel inhibitors of IRAP worthy of assessment in behavioural models of learning and memory. The analogues are devoid of AT(1) receptor agonist properties, and the carboxyamide analogue presents an opportunity to elucidate the mechanism of action of Ang IV as, like Ang IV, it inhibits IRAP, but antagonises the effects of Ang IV on isolated smooth muscle.

pKas of the conjugate acids of N-heterocyclic carbenes in water.

pK(a) values of 19.8-28.2 are reported for the conjugate acids of a large series of NHCs in water. The effects of ring size, N-substituent and C(4)-C(5) saturation on pK(a) are discussed.

Speech recognition-based and automaticity programs to help students with severe reading and spelling problems.

This study was conducted to assess the effectiveness of two programs developed by the Frostig Center Research Department to improve the reading and spelling of students with learning disabilities (LD): a computer Speech Recognition-based Program (SRBP) and a computer and text-based Automaticity Program (AP). Twenty-eight LD students with reading and spelling difficulties (aged 8 to 18) received each program for 17 weeks and were compared with 16 students in a contrast group who did not receive either program. After adjusting for age and IQ, both the SRBP and AP groups showed significant differences over the contrast group in improving word recognition and reading comprehension. Neither program showed significant differences over contrasts in spelling. The SRBP also improved the performance of the target group when compared with the contrast group on phonological elision and nonword reading efficiency tasks. The AP showed significant differences in all process and reading efficiency measures.