Characteristics of patients with bullous pemphigoid: comparison of classic bullous pemphigoid to non-bullous pemphigoid.

BACKGROUND: Bullous pemphigoid (BP) is the most common subepidermal autoimmune blistering disease. Patients occasionally present with a clinical picture of pruritus/urticaria alone for months and do not even develop blisters over time. Only few studies have investigated this subgroup of non-bullous pemphigoid (NBP). OBJECTIVE: To evaluate the demographic and clinical characteristics of BP patients with or without blisters at the time of diagnosis. METHODS: A retrospective study based on the medical records of 115 BP patients. Collected data included demographic characteristics, clinical presentation, treatment and response to treatment. RESULTS: Thirty-six patients presented with pruritus/urticaria (31.3%), and 79 presented with blisters (68.7%), with mean ages of 77.5 and 76.0, respectively, at diagnosis and an equal female:male ratio. The level of immunoglobulin E (IgE) was 4.1 times higher, and the mean blood eosinophil count was significantly increased in the pruritus/urticaria group. Remission rate at 3 months and relapse rate were similar between the groups. Median follow-up period was 9 months (range 3-18). Only 23% of the patients with pruritus/urticaria developed blisters. CONCLUSIONS: A significant number of BP patients present without blisters. We found no significant epidemiological or clinical differences from the classic BP patients aside from significantly elevated IgE and blood eosinophil levels. Similar results in larger cohort studies might be the foundation for a change in clinical protocols regarding the diagnosis and recommended treatment for the elderly presenting with pruritus/urticaria only.

Neuropsychiatric comorbidity among adolescents with psoriasis.

BACKGROUND: Psoriasis is a known risk factor for neuropsychiatric diseases among adults. Less is known about the impact on adolescents. OBJECTIVES: To investigate the association between psoriasis and neuropsychiatric comorbidity and social skills among adolescents. METHODS: A population-based cross-sectional study between 1 January 1999 and 1 January 2014 was conducted. The study included 1746 and 1366 adolescents (aged 16 to 18) with mild and moderate-to-severe psoriasis, respectively. The psoriasis patients were diagnosed by a dermatologist. Neuropsychiatric diseases were diagnosed by a neurologist and a psychiatrist, as appropriate. Social skills were evaluated using psychosocial assessment. Patients with psoriasis were compared with 884 653 healthy controls by a multivariate analysis adjusted for age, sex, country of origin, socioeconomic status, cognitive skills and body mass index. A subgroup evaluation was done for comorbidity that could only be evaluated for part of the recruitment years, using a univariate analysis. RESULTS: Overall chronic headaches (8·1% vs. 3·4%), intermediate frequency migraine (4·8% vs. 1·6%), low-frequency migraine and nonmigraine headaches (3·4% vs. 1·8%) were associated with moderate-to-severe psoriasis only compared with healthy controls [adjusted odds ratios (OR) 1·9, 95% confidence interval (CI) 1·6-2·4; 2·3, 95% CI 1·8-3·0 and 1·5, 95% CI 1·1-2·1, respectively]. Anxiety disorders (2·1% vs. 0·8%) and impaired social adjustment skills (7·5% vs. 4·2%) were also associated with moderate-to-severe psoriasis only compared with healthy controls [adjusted ORs 2·9, 95% CI 1·6-5·5 and 1·9, 95% CI 1·3-2·6 (of 466 vs. 265 023), respectively]. CONCLUSIONS: Psoriasis among adolescents is associated with neuropsychiatric comorbidity and impaired adjustment skills, depending on disease severity.

Enhanced spontaneous transmitter release is the earliest consequence of neocortical hypoxia that can explain the disruption of normal circuit function.

After the onset of an acute episode of arrested circulation to the brain and consequent cerebral hypoxia, EEG changes and modifications of consciousness ensue within seconds. This in part reflects the rapid effect of hypoxia on the neocortex, where oxygen deprivation leads to impaired neuronal excitability and abnormal synaptic transmission. To identify the cellular mechanisms responsible for the earliest changes in neocortical function and to determine their time course, we have used patch-in-slice recording techniques to investigate the effects of acute hypoxia on the synaptic and intrinsic properties of layer 5 neurons. Coronal slices of mouse somatosensory cortex were maintained at 37 degrees C and challenged with episodes of hypoxia (3-4 min of exposure to 95% N(2), 5% CO(2)). In recordings with cell-attached patch electrodes, activation of ATP-sensitive potassium channels first became detectable 211 +/- 11 sec (range, 185-240 sec; n = 6 patches) after the onset of hypoxia. Similar recording techniques revealed no alterations in the properties of Na(+) currents in the first 4 min after the onset of hypoxia. The earliest hypoxia-induced disturbance was a marked increase in the frequency of spontaneous EPSCs and IPSCs, which began within 15-30 sec of the removal of oxygen. This rapid synaptic effect was not sensitive to TTX and was present in Ca(2+)-free perfusate, indicating that the hypoxia had a direct influence on the vesicular release mechanisms. The incoherent, massive increase in miniature PSCs would be expected to deplete the readily releasable pool of vesicles in cortical terminals, and to thereby markedly distort the neuronal interactions that underlie normal circuit function.

Activation of protein kinase C increases neuronal excitability by regulating persistent Na+ current in mouse neocortical slices.

Effects of the protein kinase C activating phorbol ester, phorbol 12-myristate 13-acetate (PMA), were studied in whole cell recordings from layer V neurons in slices of mouse somatosensory neocortex. PMA was applied intracellularly (100 nM to 1 microM) to restrict its action to the cell under study. In current-clamp recordings, it enhanced neuronal excitability by inducing a 10- to 20-mV decrease in voltage threshold for action-potential generation. Because spike threshold in neocortical neurons critically depends on the properties of persistent Na+ current (INaP), effects of PMA on this current were studied in voltage clamp. After blocking K+ and Ca2+ currents, INaP was revealed by applying slow depolarizing voltage ramps from -70 to 0 mV. Intracellular PMA induced a decrease in INaP at very depolarized membrane potentials. It also shifted activation of INaP in the hyperpolarizing direction, however, such that there was a significant increase in persistent inward current at potentials more negative than -45 mV. When tetrodotoxin (TTX) was added to the bath, blocking INaP and leaving only an outward nonspecific cationic current (Icat), PMA had no apparent effect on responses to voltage ramps. Thus PMA did not affect Icat, and it did not induce any additional current. Intracellular application of the inactive PMA analogue, 4 alpha-PMA, did not affect INaP. The specific protein kinase C inhibitors, chelerythrine (20 microM) and calphostin C (10 microM), blocked the effect of PMA on INaP. The data suggest that PMA enhances neuronal excitability via a protein kinase C-mediated increase in INaP at functionally critical subthreshold voltages. This novel effect would modulate all neuronal functions that are influenced by INaP, including synaptic integration and active backpropagation of action potential from the soma into the dendrites.