Development and validation of the mastocytosis activity score.

BACKGROUND: Mastocytosis is a heterogeneous disease characterized by a clonal expansion of mast cells in various organs. The vast majority of patients suffer from signs and symptoms caused by mediator release from mast cells. Although the disease burden is high, there is currently no specific and validated instrument to measure and monitor signs and symptoms in patients with mastocytosis. OBJECTIVE: To develop and validate a disease-specific tool to measure and monitor the activity of signs and symptoms in patients with mastocytosis, the Mastocytosis Activity Score (MAS). METHODS: Nineteen potential MAS items were developed in a combined approach consisting of semi-structured patient interviews, expert input and literature research. Item selection was performed by impact analysis with 76 patients followed by a review for face validity. The resulting MAS was tested for validity, reliability and influence factors. In parallel, a US American English version of the MAS was developed. RESULTS: A total of 68 mastocytosis patients took part in the MAS validation study. The final 9-item MAS was found to have a three-domain structure ("skin," "gastrointestinal tract" and "other"), a valid total score and an excellent test-retest reliability. Multiple regression analysis revealed that disease duration, age or gender is not a significant determinant of the MAS results. CONCLUSIONS: The MAS is a disease-specific, valid and reliable patient-reported outcome measure for adult patients with cutaneous and indolent systemic mastocytosis. It may serve as a valuable tool to measure and monitor mastocytosis activity, both, in clinical trials and in routine care.

Cholinergic urticaria patients of different age groups have distinct features.

BACKGROUND: Cholinergic urticaria (CholU) is a common skin disease characterized by the development of pinpoint-sized weals and severe itch upon physical exercise. Little is known about the epidemiology of CholU. CholU can occur at any age and has the highest prevalence among young adults. As of now, it is unclear whether patients of different age show differences in the clinical manifestation of CholU, duration of disease, comorbidities or response to treatment. METHODS: Here, we analysed the demographic data and clinical characteristics including disease duration and comorbidities of 200 patients with CholU, 12-76 years of age. RESULTS: We identified two distinct types of CholU, one with early onset (EO, 71%) and one with late onset (LO, 29%). Patients with EO and LO CholU markedly differ in key characteristics: patients with EO, who had a disease onset before the age of 36, showed no gender preponderance and had a significantly higher rate of concomitant atopic dermatitis (16.9% vs 5.2%; P = .028) and higher IgE levels (295.5 vs 267.1 IU/mL; P = .020) as compared to patients with LO, who were mainly female (69%), had a shorter duration of disease (33.3 vs 63.7 months; P = .005), a higher rate of concomitant other forms of urticaria (48.3% vs 33.1%; P = .044) and a higher rate of psychiatric comorbidities (12.1% vs 1.4%; P = .001). CONCLUSION: There are two subtypes of CholU patients with different gender ratios, disease duration and comorbidities. These findings suggest that two distinct underlying pathogenetic pathways are relevant in these two subgroups of patients with CholU.

[The bioequivalence of two oral propafenone preparations]. / Untersuchungen zur Bioäquivalenz von zwei oralen Propafenon-Zubereitungen.

The bioequivalence of two oral racemic propafenone (CAS 54063-53-5) preparations was tested in an open, randomised, crossover trial with administration of single doses of 300 mg on two different occasions with a washout period of 7 days. 24 healthy, male volunteers, all proved to be rapid hydroxylators of debrisoquine, were enrolled in the trial. The concentrations of R(+)-, S(-)-propafenone and 5-hydroxypropafenone (5-OH-propafenone) were measured up to 12 h after administration by means of a sensitive and specific HPLC method that allowed the simultaneous quantification of all three substances in plasma. The results of 23 volunteers were evaluated pharmacokinetically. Main target parameters were AUC0-infinity and Cmax of both enantiomers of propafenone. Secondary target parameters were AUC0-infinity and Cmax of 5-OH-propafenone as well as tmax for R(+)- and S(-)-propafenone. The 90% confidence intervals for AUC0-infinity for R(+)-, S(-)-, and 5-OH-propafenone were 0.85-1.07, 0.83-1.10 and 0.84-1.05, respectively. The confidence intervals for Cmax were 0.81-1.12, 0.82-1.17 and 0.87-1.09 for R-, S-, and 5-OH-propafenone, respectively. The concentration maxima of both enantiomers were registered on average 15 min earlier after administration of the test preparation. This difference is of no clinical relevance. Both preparations are bioequivalent according to the criteria of the Committee for Proprietary Medicinal Products (CPMP).