Disease burden of patients with pemphigus from a societal perspective.

Introduction: Cost-of-illness studies are widely used for healthcare decision-making; however, no such study is available in pemphigus from the societal perspective. The purpose of this analysis was to estimate annual cost-of-illness per patient with pemphigus from a societal perspective. Areas covered: Between 2014 and 2017, a multicenter, cross-sectional study was carried out. Consecutive pemphigus patients aged ≥18 years were recruited at all four university dermatology departments in Hungary. Direct and indirect costs were calculated, including costs for treatments, outpatient visits, hospital admissions, informal care, travel costs and productivity loss. Generalized linear model was used to analyze predictors of costs. Atotal of 109 patients with pemphigus enrolled with amean age of 57.1 (SD 14.8) years. Total cost per pemphigus patient was €3,995 (SD €7,526) peryear, with productivity loss (58%) and informal care (19%) accounting for the majority. Annual means of 189 and 41 working hours were lost due to absence from work and reduced productivity, respectively. Younger age and pemphigus vulgaris were associated with higher costs (p < 0.05). Expert opinion: This is the first cost-of-illness study applying the societal perspective in pemphigus. Our results indicate a substantial economic burden on society, mainly driven by productivity loss and informal care.

Improvement of clinical and immunological parameters after allergen-specific immunotherapy in atopic dermatitis.

BACKGROUND: Allergen immunotherapy (AIT) is considered a curative treatment in some atopic diseases, but in AD contradictory clinical results exist and the action of AIT has not been elucidated. In the literature, there is no evidence for parallel investigations of permeability barrier, cutaneous and blood immune responses after AIT in AD. OBJECTIVES: The objective was to investigate immune parameters in the blood and skin and to detect clinical and barrier changes after AIT in AD. METHODS: Mild-to-moderate AD patients (n = 14) with concomitant allergic rhinitis to house dust mites were selected. All patients received topical treatment, while eight patients were randomly selected for adjuvant AIT also. At baseline and after 6 months, clinical, barrier and immunological investigations (serum and skin tests) were performed. In selected patients, biopsies from atopy patch tests (APTs) were analysed by immunohistochemistry for AD-relevant immune cells and mediators. RESULTS: In the adjuvant AIT group, clinical parameters and barrier functions improved significantly. Blood immune parameters displayed no significant changes. Post-AIT APT became negative in all patients in the AIT group, but remained positive in the non-AIT group. Cutaneous dendritic cell and T-cell recruitment decreased significantly after allergen challenge in the AIT group, but no significant changes in skin or serum immunoglobulin E levels or prick test (SPT) reactivity were detected. CONCLUSIONS: Allergen immunotherapy is a beneficial adjuvant treatment for sensitized AD patients. AIT improves not only clinical symptoms, but also permeability barrier functions. The effect of AIT on sensitization should be detected by APT, not by SPT.

DLQI-R scoring improves the discriminatory power of the Dermatology Life Quality Index in patients with psoriasis, pemphigus and morphea.

BACKGROUND: The Dermatology Life Quality Index (DLQI) rates 'not relevant' responses (NRRs) as the item on the questionnaire having no impact on the patients' lives at all. The DLQI-Relevant (DLQI-R) is a recently developed scoring that adjusts the total score of the questionnaire for the number of NRRs indicated by a patient. OBJECTIVES: To compare the discriminatory power of the original and DLQI-R scoring approaches in terms of absolute and relative informativity. METHODS: Cross-sectional data from 637 patients with morphea, pemphigus and psoriasis were used for the analyses. To assess absolute and relative informativity, Shannon's index and Shannon's evenness index were calculated for the 10 items on the questionnaire and for DLQI and DLQI-R total scores. RESULTS: Mean DLQI and DLQI-R scores of patients were 6·13 vs. 6·91. In the subset of patients with NRRs (n = 261, 41%), absolute informativity was higher with the DLQI-R scoring for all eight items with NRR options in all three conditions. The DLQI-R exhibited a better relative informativity in 8, 8 and 6 items in pemphigus, morphea and psoriasis, respectively. The DLQI-R led to an improvement in average item-level informativity in all DLQI score bands up to 20 points. Regarding total scores, the DLQI-R produced both a higher absolute and relative informativity in all three conditions. CONCLUSIONS: In patients with morphea, pemphigus and psoriasis, DLQI-R scoring improves the discriminatory power of the questionnaire by benefiting from the additional information in NRRs. DLQI-R scoring may be useful both in clinical practice and research. A scoring chart has been developed to aid physicians with scoring. What's already known about this topic? The original scoring of the Dermatology Life Quality Index (DLQI) rates 'not relevant' responses as the item of the questionnaire having no impact on the patients' lives at all. DLQI-Relevant (DLQI-R) is a new scoring developed in 2018 that adjusts the total score of the questionnaire for the number of 'not relevant' responses indicated by patients. The discriminatory power of the DLQI-R compared with the DLQI has not yet been investigated. What does this study add? In patients with psoriasis, pemphigus and morphea, DLQI-R scoring improves the discriminatory power of the questionnaire by benefiting from the additional information in 'not relevant' responses. What are the clinical implications of this work? DLQI-R scoring may help to more accurately quantify patients' health-related quality of life both in clinical practice and research. A scoring chart has been developed to aid physicians with scoring.

Patient-assigned health utility values for controlled and uncontrolled pemphigus vulgaris and foliaceus.

BACKGROUND: The assessment of health-related quality of life (HRQoL) in patients with pemphigus is now of increasing interest due to the availability of highly effective new therapies. Preference-based HRQoL values or health utilities required for medical and financial decision-making are not yet available directly from pemphigus patients. OBJECTIVE: To obtain health utility values for current health and hypothetical health states from the perspective of pemphigus patients. METHODS: A cross-sectional questionnaire survey was carried out with pemphigus patients. Disease severity was rated by Autoimmune Bullous Skin Disorder Intensity Score (ABSIS). Patients were asked to evaluate their current health as well as three common hypothetical pemphigus health states [uncontrolled pemphigus vulgaris (PV), uncontrolled pemphigus foliaceus (PF) and controlled PV/PF] by using composite time trade-off (cTTO). Multiple regression was applied to explore determinants of utility values. RESULTS: Responses of 108 patients (64.8% women, mean age 57.4 years) were analysed. Mean ABSIS score was 11.6. The mean utility values for the hypothetical uncontrolled PV, uncontrolled PF and controlled PV/PF health states were 0.41, 0.52 and 0.66 with cTTO. The mean cTTO scores for current health were higher compared with the hypothetical health states (0.76; P < 0.001). Patients with higher ABSIS, worse pain intensity scores and those having a caregiver reported lower utility values for current health (P < 0.05). CONCLUSIONS: In pemphigus, HRQoL impairment expressed in utility values seems to be considerable, especially in comparison with other chronic dermatological conditions (e.g. psoriasis, atopic eczema, chronic hand eczema). These health utilities inform physicians, policymakers and funders about the overall extent of health loss in pemphigus and provide evidence to guide medical decisions and cost-effectiveness analyses of treatment strategies. Future research is needed to evaluate the caregiver burden in pemphigus.

Validity of the EQ-5D in patients with pemphigus vulgaris and pemphigus foliaceus.

BACKGROUND: No studies to date have employed the EuroQoL EQ-5D questionnaire to assess health-related quality of life (HRQoL) in patients with pemphigus. OBJECTIVES: To evaluate the HRQoL of patients with pemphigus by the EQ-5D and to analyse the convergent and known-groups validity of the EQ-5D in this patient population. METHODS: Between 2014 and 2017, a multicentre cross-sectional study was carried out. Outcome measures included the five-level EQ-5D (EQ-5D-5L), Dermatology Life Quality Index (DLQI), Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) and an average pain intensity visual analogue scale (VAS) for the past 3 months. RESULTS: In total, 109 consecutive patients with pemphigus participated in the study (mean age 57 years; 64% women). Among the EQ-5D dimensions, the most problems were reported regarding pain/discomfort (50%), mobility (43%) and anxiety/depression (43%). No significant difference was found in mean EQ-5D index scores between patients with pemphigus vulgaris and those with pemphigus foliaceus (0·81 vs. 0·86, P = 0·14). The mean EQ-5D index scores of patients with limited, moderate, significant and extreme pemphigus were 0·88, 0·82, 0·72 and 0·67, respectively (P = 0·001). The number of comorbidities was associated with greater impairment in EQ-5D index scores (P < 0·001). DLQI (rs = -0·62, P < 0·001) and the average pain intensity VAS (rs = -0·59, P < 0·001) more strongly correlated with the EQ-5D index scores than did ABSIS (rs = -0·40, P < 0·001). CONCLUSIONS: This is the first study employing the EQ-5D questionnaire in pemphigus. The EQ-5D is a valid measure of HRQoL in patients with pemphigus that can be useful both in clinical practice and in economic evaluations to assess the health gains associated with new effective treatments.

AZFc deletion detected in a newborn with prenatally diagnosed Yq deletion.

A case of prenatally diagnosed Yq deletion is described. Fluorescence in situ hybridisation (FISH) was used to identify the abnormal chromosome and to exclude mosaicism. Based on the cytogenetic result and the ultrasound investigation the pregnancy was continued. A newborn with normal male genitalia was delivered. Microdeletion analysis of the Yq showed the absence of the AZFc region. This type of deletion has been described as being associated with azoospermia or oligozoospermia with a progressive decrease of sperm number over time. Long-term andrological follow-up of the newborn will be necessary with eventual cryoconservation of sperm at early adulthood. The present report proposes that AZF analysis combined with FISH has an important role in accurate genetic counselling in sex chromosome anomalies.

Fluorescence in situ hybridization of chorionic interphase cells for prenatal screening of Down syndrome.

OBJECTIVE: Our purpose was to determine the usefulness and reliability of fluorescence in situ hybridization on interphase chorionic villi cells in the prenatal diagnosis of Down syndrome. METHODS: A total of 336 samples of chorionic villi were analysed by direct chromosome preparation and FISH with a DNA probe specific to chromosome 21. The samples were obtained as part of the routine obstetric investigation and management. RESULTS: The sampling and direct karyotyping was successful in all cases. At least 50 cells were valuable by FISH in 331 of 336 samples. Both methods showed Down syndrome in 12 cases. The follow-up investigations showed that there was no false-negative or false-positive result following these procedures. CONCLUSION: Based on these results and the fact that it is possible to analyse by interphase FISH at least ten times more cells than by conventional cytogenetic methods, and these cells originate from different tissues of chorionic villi, it is concluded that FISH increases the reliability of the diagnosis. Nevertheless, more data are needed for correct statistical analysis. Since this method is cheaper and gives diagnosis earlier than cell culture, the combination of direct chromosome preparation and FISH on chorionic villi is offered for prenatal Down syndrome screening.

[Respiratory insufficiency amd pregnancy in cystic fibrosis]. / Légzési elégtelenség és terhesség cisztás fibrosisban.

Cystic fibrosis is one of the most serious genetic disorders. The survival and the quality of life of our patients have also been improved in the last decade. The number of patients entering the reproductive age is increasing. The young women in good somatic condition may undertake pregnancy. The desire for a full life and for a child may arise at patients with respiratory insufficiency too. Authors list the maternal and fetal risks of the pregnancy in cystic fibrosis by a case report. As a result of multidisciplinary team work a boy was born. The mother died in progressive and uninfluencable respiratory insufficiency being on waiting-list for lung transplantation 15 months after the delivery.

In utero allogeneic hematopoietic stem cell transplantation to induce tolerance.

We studied the efficacy of in utero hematopoietic stem cell transplantation and the ability of such transplantation to induce tolerance in a fetal normal mouse allogeneic model. In 9 of the 162 surviving recipients (5.6%), cells of donor origin were detected after birth. The highest engraftment rate was achieved by transplanting fetal liver cells in a relatively high dose (> 10(6) cells/fetal gram). Skin grafting was performed to determine the presence of prenatally induced tolerance. Only those mice which showed evidence of chimerism became tolerant to skin derived from the prenatal donor's strain while remaining competent to reject a skin transplant from a third strain. Tolerant mice could have significant chimerism reestablished by utilizing monoclonal antibody specific for the recipient H-2 antigen as conditioning for IV fetal stem cell retransplantation.

[Intrauterine management of Rh-alloimmunization]. / Az Rh-alloimmunizáció intrauterin kezelése.

The authors report the strategy of invasive management of Rh alloimmunisation in pregnancy. From the 34 pregnancies 6 were monitored by amniocenteses, 11 by fetal blood sampling, and 4 with combination of the two above mentioned diagnostic procedures. In 13 cases the fetuses were treated with intrauterine intravascular blood transfusions. All the procedures were ultrasound guided. The fetal blood sampling and the transfusions were carried out by puncturing the umbilical vein or artery. For transfusions, maternal blood was used in case of identical blood type, otherwise adult Rh negative, filtered, washed, irradiated blood was transfused. They report the complications as well, giving the cause of their fetal losses in details. There were no maternal complications observed. Out of the 34 pregnant women 25 had healthy newborns, which number is acceptable in this disease with a very high mortality rate. The authors underline that the technique of fetal blood sampling and intrauterine transfusion if needed is necessary in the management of Rh alloimmunised pregnancies.

[Fluorescence in situ hybridization in prenatal diagnosis. First experiences]. / A fluoreszcens in situ hibridizáció alkalmazása a praenatalis diagnosztikában. Elsö tapasztalatok.

The authors examined the potential use of non-radioactive in situ hybridization in prenatal screening. Probes for chromosomes 18, 13/21, 21 and X were applied on fourteen samples of peripheral lymphocytes and nine samples of chorionic villi. The aim of the study was to compare the analyzability of the two different DNA probes for chromosome 21 on six samples of chorionic villi. Six of the nine samples of chorionic villi were hybridized with probes specific for chromosome 21 and all six cases were diagnosed properly. However, we need more data to establish a screening protocol for routine prenatal cytogenetics.

Stem cell transplantation.

Modern physicians desire not only to treat but to cure congenital diseases. In a wide variety of diseases, bone marrow transplantation can be the tool of final cure. The limitations and risks of this procedure have motivated researchers to search for an earlier and safer method of treatment. Special features of fetal immune systems make it possible to perform the transplantation during fetal life using fetal hematopoietic stem cells, thus avoiding many of the side effects of bone marrow transplantation in neonatal life. We review the experimental work done with animal models in this field and the human trials that have been published recently.

[Results of prenatal cytogenetic screening at the Prenatal Genetic Center of the Postgraduate Medical University between 1980-1990]. / Az Orvostovábbképzö Egyetem Prenatális Genetikai Központjának eredményei a terhesség alatti citogenetikai szürés terén 1980 és 1990 között.

Evaluation of prenatal cytogenetic diagnosis by Genetic Center of Postgraduate Medical University in 1980 and 1990. Between 1980 and 1990, 1039 amniocenteses (AC), 1263 chorionic villus samples (CVS), and 30 fetal blood sampling were performed for cytogenetic reasons. The rate of chromosome abnormalities were 5.5 per cent in the first trimester CVS, 5.2 per cent in the second trimester CVS, and 3.1 per cent in AC. The Down syndrome was the most frequent abnormality (46 fetuses) and the next was the Edwards syndrome (15 cases). It was established that though the case number is fourteen times more than the beginning of this decade, this was enough only for screening women 39 or over. During this period several new methods were introduced making possible the diagnosis from 9th week of pregnancy until term. Among these methods the CVS has not only become an alternative to the AC but now it is the most frequent procedure in our laboratory. Though most pregnants are still referred for prenatal cytogenetic investigation because of their advanced age, the authors search for other risk factors which would make possible screening in younger women, too.

Tetraploidy in human placenta. A dilemma in molar and non-molar pregnancies.

17 cases of partial molar pregnancy were analysed cytogenetically by the direct-preparation method. Eight partial moles were triploid, 7 diploid/tetraploid mosaic, and 2 tetraploid. In the course of prenatal cytogenetic screening, out of 1,263 chorionic villus samplings, 2 tetraploid and 1 diploid/tetraploid cases were found. These cases of partial moles do not fit into the usual patterns of triploid partial moles. The findings presented here suggest that different causative factors may be involved in the origin of molar degenerations. These results also call to attention that tetraploidy is an existent and relatively common abnormality.

[Sneddon syndrome (livedo and cerebrovascular lesion)]. / Sneddon-syndroma (livedo és cerebrovascularis laesio).

A typical syndrome going on with skin (livedo racemosa generalisata) and brain (ischemic vascular) involvement is presented. Symptoms of skin and nervous system are made known in detail, as well as possibility of early diagnosis and standpoint of treatment.

[Transabdominal chorion aspiration in the second pregnancy trimester]. / Transabdominalis chorion-aspiráció a terhesség második trimesterében.

The authors report their experiences with 377 transabdominal chorionic villi samplings performed in the second trimester of pregnancy, between 1987-1989. They used the double needle technique with continuous ultrasound guidance. In every case they could get a sufficient amount of villi from one puncture, and there was no unsuccessful direct chromosome-preparation. The obstetrical complications of the procedure were measured by the analysis of the outcome of the first 300 pregnancies intended to continue: the abortion rate after the transabdominal chorionic villi sampling seems to be lower, than after amniocentesis.

Prenatal cytogenetic study of translocation carriers.

A total of 37 prenatal diagnoses were analysed: 10 observations in which one of the parents carried a Robertsonian translocation and 27 observations in which one a reciprocal translocation was carried by one of the parents. The segregations of the inherited chromosome structural rearrangements were analysed in relation to the methods of ascertainment of the anomaly in the family, and the types of rearrangement. The mode of ascertainment proved to be a very useful indicator of the risk: those cases ascertained through abnormal livebirths had a 44% risk in our series, but there was no unbalanced fetus in the group ascertained through recurrent abortions.

[Fetal diagnosis of Edwards syndrome]. / Az Edwards-syndroma fetális diagnosztikája.

Eight cases of Edward's syndrome were found prenatally by cytogenetical analysis of 1680 pregnant women. It has been estimated that after Down's syndrome Edwards's syndrome is the most frequently encountered chromosomal abnormality. This syndrome is associated with high rate of anomalies detectable by ultrasound (e.g. omphalocele, polyhydramnion, growth retardation). Here it is discussed in relation with sonographical findings related to Edwards's syndrome and representing clear indications for chromosomal analysis. The authors call attention to the importance of the diagnosis of Edward's syndrome at each gestational age.