Oral status and dental treatment needs in patients with Epidermolysis Bullosa - a cross-sectional study.

The aim of the study was to summarize the experience for providing oral health care in children with epidermolysis bullosa (EB) treated in Central Research Institute of Dentistry and Maxillofacial Surgery in 2013-2014. Seven EB patients (5 female and 2 male aged 5-17) with dystrophic form of EB were included in the study. Oral status was recorded (oral hygiene, presence of enamel hypoplasia and intraoral soft tissue lesions). Dental treatment provided included teeth extractions under conscious sedation (6 cases), teeth treatment (both conventional and ART methods) (5 cases) and preventive program (5 cases). All 7 dystrophic EB patients presented with generalized enamel hypoplasia in both primary and permanent dentition. In these patients one should consider using non-adhesive face dressings and careful suction pipe positioning as well as applying liniments on cotton rolls not to cause both intraoral and extraoral soft tissue lesions. Sixteen milk teeth were extracted under conscious sedation, in 3 cases the procedure caused significant vestibular scarring. Twelve teeth were treated mostly by ART method (n=1 0) as limited mouth opening made conventional treatment impossible. Dental treatment in dystrophic EB is a real challenge for pediatric dentist. This group of patients requires a special dental rehabilitation plan as they present with generalized enamel hypoplasia and have significant risk of intraoral lesions.

Epidermolysis bullosa (EB) is a genetic disorder, characterized by blisters on skin and mucosal surfaces even upon light mechanical damage. EB is caused by genetic mutations in at least seven proteins on the basement membrane zone, which is the boundary between the epidermis and the dermis. There are many types of EB differing in clinical and genetic aspects, and the prognosis varies depending on the EB type. There are largely three types of EB, categorized by the electron-microscopic location of the blisters. The blisters form within the epidermis in epidermolysis bullosa simplex, in the lamina lucida in junctional epidermolysis bullosa, and just beneath the basal lamina in dystrophic epidermolysis bullosa. To date, there is no medication or treatment that cures EB or completely prevents the blisters, so generally symptomatic treatment is performed. EB patients must always be cautious, for blisters can form at the slightest injuries, and the patients must be dealt with gently. Injuries and infections have to be prevented and treated, and deficient nutrients must be supplied during dental treatment period. Some patients may experience pain when swallowing food or dental treatment due to blisters and resulting scars in the mouth, pharynx, and esophagus. Recently, two pediatric patients were diagnosed with EB at Pusan National University Hospital and visited the Department of Pediatric Dentistry for oral care and dental treatment. The treatment results are reported here. [J Korean Dis Oral Health Vol.8, No.2: 122-126, Dec 2012]

Epidermolysis bullosa (EB) consists of a group of genetic hereditary disorders in which patients frequently present fragile skin and mucosa that form blisters following minor trauma. More than 20 subtypes of EB have been recognized in the literature. Specific genetic mutations are well characterized for most the different EB subtypes and variants. The most common oral manifestations of EB are painful blisters affecting all the oral surfaces. Dental treatment for patients with EB consists of palliative therapy for its oral manifestations along with typical restorative and periodontal procedures. The aim of this article is to describe two dental clinical treatments of recessive dystrophic EB cases and their specific clinical manifestations. The psychological intervention required during the dental treatment of these patients is also presented.

Quality of life (QoL) has not been evaluated in Indian patients having epidermolysis bullosa (EB). The aims of the study were to measure health-related QoL in Indian patients having EB using the quality of life in epidermolysis bullosa (QoLEB) questionnaire, and to find its correlation with clinically measured disease severity. In this observational cross-sectional study, the QoLEB questionnaire was translated from English to Hindi (QoLEB-Hin) and culturally adapted without a change in concept following standard guidelines. QoLEB-Hin and three clinical scores that have been independently validated in EB, that is, Birmingham Epidermolysis Bullosa severity score (BEBs), Instrument for Scoring Clinical Outcomes of Research for Epidermolysis Bullosa (iscorEB) and Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI), were administered to EB patients/their parents in the presence of an expert. This was followed by validity and correlation studies. Fifty-four patients were recruited (19-females, 35-males; median age 5 years, range 0.025-36 years and 12 patients with an age >13 years). The parents answered the questions for 42 patients (age <13 years). Dystrophic epidermolysis bullosa was diagnosed in 32 (59.2%) patients (dominant dystrophic epidermolysis bullosa [DDEB]-19 [35.2%] and recessive dystrophic epidermolysis bullosa [RDEB]-13 [24.1%]). Junctional epidermolysis bullosa (JEB) and epidermolysis bullosa simplex (EBS) were each diagnosed in 11 (20.4%) patients. The mean ± standard deviation (SD) of QoLEB-Hin score of all epidermolysis bullosa patients was 11.3 ± 7.6 (range 0-28; median and interquartile range [IQR], 10, 10) and reflected an overall moderate degree of affliction on QoL of patients. Mean ± SD of QoLEB-Hin scores for EBS, JEB, DDEB and RDEB were 5.4 ± 3.7 (range, 1-13; median and IQR, 6, 6), 11 ± 6.2 (range, 1-22; median and IQR, 10, 6), 9 ± 5.7 (range, 0-19; median and IQR, 10, 10) and 20.1 ± 6.4 (range, 12-28; median and IQR, 19, 12.5), respectively (P < 0.001, Kruskal-Wallis analysis of variance). Cronbach's alpha coefficient of 0.946 was obtained for all items indicating excellent internal consistency and reliability. Mean sample adequacy was 0.91; absolute fit based off diagonal values was 0.99; indices root mean square error of approximation and root mean square residual were 0.04 and 0.05, respectively, and Tucker Lewis index was >1 indicating overfit. The mean time taken to complete the questionnaire was 6.1 min (range, 6-8 min). QoLEB-Hin correlated significantly (P < 0.001) with BEBs (ρ = 0.79), iscorEB (ρ= 0.63) and EBDASI (ρ = 0.77). Three multiple linear regression models were used to ascertain the strength of relationship between QoL-Hin, and BEBs, iSCOREB and EBDASI, respectively, after adjusting for age, gender and disease subtype. The EBDASI clinical score accounted for approximately 74% (R2 = 0.736, P < 0.001) of the variability in QOL-Hin, as compared to 73% and 55% by BEBs (R2 = 0.731, P < 0.001) and iscorEB (R2 = 0.545, P < 0.001), respectively. Parents filled out the questionnaires for many patients and probably led to an overall moderate degree of affliction of QoL. Comparison with Dermatology Life Quality Index and other QoL scores were not done in this study. Furthermore, the scoring was done at one point in time, and test-retest measurements could not be performed. This study validated QoLEB-Hin in an Indian population finding an overall moderate reduction in QoL due to EB. Maximally affected QoL was seen in patients with RDEB. Furthermore, QoLEB-Hin had a variable positive correlation and association with all clinical severity assessment scores.

Epidermolysis bullosa (EB) is a genetic disorder with continuous formation of blisters and erosions in the skin and mucous membranes as well as multi-systemic involvement. Patients are at high-risk of malnutrition due to decreased food intake and increased nutrient demand. This cross-sectional retrospective study evaluated the daily caloric intake and nutritional status of pediatric patients with EB at a specialized clinic through anthropometric measurements and estimation of the daily intake by 24-hour dietary recall. We used the Waterlow and World Health Organization (WHO) malnutrition classification schemes. Descriptive statistics were used. We included 17 patients with a mean age of 8.4 years (SD 4.6), 82.3% had malnutrition. Those with more severe subtypes, junctional and recessive dystrophic EB, had acute superimposed on chronic malnutrition (100% and 63.4%), wasting (100% and 72.6%), and stunting (0% and 54.4%) more frequently, respectively. Most patients required supplementation (caloric 76.4% and vitamin/mineral 100%). We concluded that there is a high frequency of malnutrition in our EB patients. Although their energy requirements is calculated to be increased in 100-150% of the estimate, our patients only reach 73.1% of that, thus requiring supplementation. Patients with more severe subtypes of EB had chronic malnutrition more frequently. Even though malnutrition is closely linked to wound healing and adequate growth and development of patients, there are few studies about nutrition in EB worldwide. We believe evaluating the nutritional status of these patients is the first step to identifying deficiencies, offering adequate comprehensive medical care and establishing nutritional interventions in a timely manner.

This study describes ophthalmologic and systemic clinical findings in different subtypes of epidermolysis bullosa (EB) establishing genotype-phenotype correlations. A cross-sectional study was conducted in 58 patients with EB together with the Dystrophic Epidermolysis Bullosa Research Association, Chile. Data were stratified by major subtypes such as "simplex epidermolysis bullosa" (EBS), "junctional epidermolysis bullosa" (JEB), "recessive and dominant dystrophic epidermolysis bullosa" and "dominant dystrophic epidermolysis bullosa" (DDEB), and "Kindler syndrome" (KS). The diagnosis was confirmed by skin immunofluorescence mapping and genetic testing. Best-corrected visual acuity, corneal erosions, corneal scarring, symblepharon, blepharitis, ectropion, limbal stem cell deficiency, and esophageal involvement were assessed. Clinical outcome was based on the presence of corneal involvement attributable to EB. The most common ocular manifestations were corneal erosion/scarring and recurrent erosions. Frequencies of the EB subtypes were as follows: 17% EBS, 12% JEB, 16% DDEB, 53% recessive and DDEB, and 2% KS. Patients with EBS and DDEB did not reveal ocular involvement. Patients with recessive dystrophic epidermolysis bullosa (RDEB) were most affected by the disease showing corneal involvement in 16 cases, whereas 2 patients with JEB and the single KS case also showed corneal disease. Before their visit, 24 patients had undergone esophageal dilation, 23 of them with RDEB and 1 with KS. Although ophthalmic complications are common in EB, the incidence varied with the EB subtype. We also establish the correlation between esophageal and corneal involvement in RDEB.

Epidermolysis bullosa (EB) is a rare genetic disorder that causes extreme skin fragility, chronic pain, and functional impairment, with major psychosocial and economic consequences. Health-related quality of life (HRQoL) data is critical to capture the full burden of EB. Health utilities derived from preference-based generic instruments such as the EQ-5D-5L provide standardized health status utility values that enable cross-disease comparisons and provide input data for cost-utility analyses to inform resource allocation. There is a notable lack of multinational, up-to-date utility data for EB. This cross-sectional study aimed to assess HRQoL in adults with EB across seven European countries (Austria, Bulgaria, Germany, Hungary, Italy, France, and Spain) using the EQ-5D-5L. A total of 328 adults with EB participated in the survey, 61% were female, 37% were between 18 and 30 years old and 46% had dystrophic EB. Based on self-reported symptoms, 58% were classified as severe EB. Pain/discomfort was the most affected EQ-5D-5L dimension (92% reporting problems; 27% severe or extreme). The mean EQ-5D value (health utility) was 0.63 (SD 0.32), ranging from 0.57 in Spain to 0.71 in Bulgaria. Patients with severe EB reported significantly lower utilities than non-severe cases (0.52 vs. 0.78, p < 0.001). Mean EQ VAS score was 60 (SD 23.2). Compared to general population norms, EB patients in all countries had markedly lower HRQoL (p < 0.005), with large effect sizes for the EQ-5D value (Cohen's d ≥ 0.8). Symptomatic burden and functional deterioration were the primary drivers of HRQoL impairments. This multinational study provides the most extensive and current health utility data for adults with EB in Europe. Findings reveal the profound HRQoL impairment in EB, particularly in severe cases. These standardized utility values fill a major evidence gap, supporting their use in health economic evaluations, cross-disease comparisons, and policy development.

Epidermolysis bullosa (EB) is a rare disorder characterized by recurrent blisters on the skin and oral mucosa, occurring spontaneously or after minor trauma. Evaluate the oral health status of children with EB and parents' perceptions of its impact on their child's and family's quality of life. A cross-sectional study with age-matched groups was conducted with 42 children (14 with EB and 28 without EB), aged 2-10 years, along with their parents/guardians. Participants were recruited from a reference center and a school clinic. Data demographic and socioeconomic were collected. Oral health-related quality of life (OHRQoL) was measured using the Parental-Caregiver Perceptions Questionnaire (P-CPQ-short form) and Family Impact Scale (FIS). Oral examination included evaluation of gingival condition, malocclusions, dental caries, and oral lesions. Statistical analysis included Chi-square, Mann-Whitney, t-test, and Kruskal-Wallis tests (α = 5%). Children with EB had significantly higher gingival and plaque indices (p = 0.001; p < 0.001). Parents reported worse OHRQoL for children with EB, especially in "oral symptoms" and "functional limitations" (p < 0.001). FIS scores were similar between groups (p > 0.05). Oral lesions were significantly associated with poorer OHRQoL (p = 0.001). Oral lesions were responsible for impacts experienced in children's daily lives, with significant negative effects occurring through symptoms.

Background: Epidermolysis bullosa (EB) is an inherited genetic disease affecting skin adhesion at dermal or epidermal level or in the basement membrane zone. EB is present in three major forms: simplex, junctional and dystrophic. This latter is very often associated to non-cutaneous manifestation such as gastrointestinal complication and renal damage. Aim of this study was to classify EB patients based on an assigned severity score and individuate precipitating factor, such as HLA predisposing to gluten sensitivity, responsible of the different course of the extracutaneous manifestation of the pathology. Methods: By using a cross sectional design, 36 EB patients were screened based on the Birmingham severity score and HLA typing was performed in order to discover possible associations. HLA typing test was performed by PCR and statistical method of analysis was the χ2 test. Controls (n=341) were healthy volunteer subjects. Results: From a total of 36 patients, 24 were diagnosed of the more sever form of EB, the dystrophic one. The assigned scores ranged from 11 to 90, while the 12 simplex patients received a score from 0-2. In regard to HLA typing, we found that in EB patients the 21.62% expressed a DQ2.2 HLA, while controls only 5.87% (P<0.0005 χ2 test). No statistically significant difference was found among the other aplotypes. Conclusion: Although, no difference was found in regard to HLA-DQ2.5, the strongest aplotype associated to celiac disease, we found that in EB patient there was a higher incidence of HLA-DQ2.2 that in a condition of chronic intestinal inflammation, as in these patients is likely to be, may predispose to sensitivity to gluten ultimately leading to immune mediated-organ damage.

Inherited epidermolysis bullosa: An update and suggested dental care considerations

Epidermolysis bullosa (EB) is a genodermatosis caused by mutations in the proteins of the dermal-epidermal junction, altering the epithelial cohesion, and generating blisters and shedding of skin and mucous membranes. To describe the demographic and clinical characteristics, as well as the main complications of patients with EB attended at the National Institute of Pediatrics, in Mexico City. An observational, descriptive, retrospective and cross-sectional study was conducted in patients under 18 years of age with diagnosis of EB. Patients with incomplete, purged or archived records were excluded. We included 35 patients, 17 men and 18 women with an average age of 8.94 ± 4.9 years. Patients were classified as dystrophic EB (71.4%), EB simplex (17%), junctional EB (2.9%) and Kindler syndrome (2.9%). All patients presented skin manifestations, followed by manifestations in oral mucosa (74.3%), nutritional (54.2%), gastrointestinal (51.4%), hematological (40%), ophthalmological (37.1%), musculoskeletal (34.2%) and psychosocial symptoms (34.2%). The degree of severity was variable according to the subtype; junctional EB and dystrophic EB are those that generate greater affection and comorbidity. EB is a serious multisystem genetic disease, which is why it requires an early diagnosis and a timely detection of complications.

The integration and long-term success of dental implants exploit the unique biology of the oral cavity, which allows for osseous incorporation of a biomaterial and its long-term health within a bacteria-laden oral milieu.1 The delicate balance of defense and repair mechanisms underlying this unique environment may be challenged by various factors that can act both locally and/or systemically, thereby increasing the risk of implant loss and jeopardizing the long-term success of inserted implants. Local risk factors that are present in the oral cavity and systemic risk factors that have the potential to affect oral health on a systemic level can compromise implant treatment at all stages of treatment delivery by: (a) complicating surgical procedures and other invasive measures required during treatment; (b) compromising the process of tissue healing following implant insertion/increasing the risk of wound infection; and (c) contributing to the deterioration of long-term peri-implant health and tissue stability (Table 1). Reduced bone healing Reduced implant stability Reduced bone remodeling Reduced angiogenesis Reduced bone regeneration Acquired immunosuppression Hypovascularity Iatrogenic immunosuppression Reduced tissue regeneration Hypovascularity hypoxia Leukocyte dysfunction Conditions that interfere with invasive procedures, which include poor general health status (https://www.asahq.org/resources/clinical-information/asa-physical-status-classification-system) as a result of severe systemic disease, may impact upon implant surgery, healing, and maintenance. These are mostly cardiovascular conditions that can place the patient at high risk during surgery, irrespective of the nature of the intervention. Bleeding disorders, which may be innate or acquired, as well as attributable to the use of anticoagulants, may also complicate invasive measures. While the former are considered to be relatively rare, the latter may have a significant impact on daily implant treatment in an aging population. All these conditions can also have a negative impact on long-term peri-implant health and maintenance of peri-implant tissues as a result of compromised vascularity, as well as alterations in the immune defense or repair capacity of peri-implant tissues. The increasing patient demand for implant-based treatments in conjunction with a demographic shift of the patient population has resulted in a growing body of literature dealing with an increasing number of patients presenting with medical conditions. A recent cross-sectional analysis indicated that almost 90% of patients aged > 65 years were taking medication for underlying systemic diseases, which could jeopardize implant success.2 The advent of new treatment modalities, such as antiresorptive drugs or monoclonal antibody therapies, adds to the number of potential risk factors,3 leading to an increasing challenge for the provision of implant-based treatments in the future. The aim of this narrative review was therefore to analyze the importance of systemic and local conditions as risk factors for implant loss by critically evaluating the available evidence. During evaluation of the available literature, it was obvious that the term "implant loss" was used to a much lesser degree than "implant failure." Very few reports clearly defined implant failure as implant loss, but the context in which this term has historically been used indicates that implant failure was synonymous for implant loss. It is only in the last decade or so that definitions of implant failure have been published, and not until the 2017 World Workshop on Periodontal and Peri-Implant Disease Classification was an international definition agreed upon.4 One of the major reasons for implant loss is the progressive loss of peri-implant bone support. Therefore, marginal bone loss was also included in the analysis. As progressive crestal bone loss around implants in the absence of clinical signs of soft tissue inflammation is rare,5 reported radiographic bone loss was considered in conjunction with clinical peri-implant parameters (where provided) in the individual reports in order to assess the prognostic relevance of the findings. The effect of cardiovascular conditions on implant treatment has been mostly analyzed in cross-sectional cohort studies. In these reports, 15.6%-37%6-8 of patients were affected by cardiovascular diseases. Two recent multivariate analyses of large cohorts consisting of > 6300 and > 22 000 patients did not identify cardiovascular conditions as significant risk factors for implant loss6 or peri-implant pathology.9 This is in line with other cross-sectional studies of smaller cohorts.10-13 Cardiovascular conditions may, however, be associated with the maintenance of long-term peri-implant tissue health. Patients with diseased implants have shown a higher likelihood of cardiovascular comorbidity,8 and a recent prospective study of 44 patients with fixed mandibular prostheses demonstrated an association between cardiovascular disease and increased radiographic peri-implant bone loss.14 The available evidence currently suggests that cardiovascular conditions are not a major risk factor for implant loss. Although the radiographic bone loss reported had not been classified as progressive, cardiovascular disease should be taken into account in maintenance protocols as a potential comorbidity15 that may affect long-term peri-implant tissue health. Bleeding disorders can be innate, such as hemophilia A/B and von Willebrand–Jürgens Syndrome, or acquired during end stage liver disease, with subsequent deterioration of coagulation factors and platelet counts. The placement of implants in patients with hemophilia is rarely documented in case reports.16, 17 In contrast to this, patients with iatrogenic bleeding disorders as a result of anticoagulation therapy have been studied more frequently. Depending on the underlying disease, anticoagulation therapy may encompass antiplatelet drugs, vitamin K antagonists, or direct oral anticoagulants. There is widespread agreement that anticoagulation therapy with antiplatelet drugs or vitamin K antagonists should not be discontinued for dental surgical procedures, as long as a single drug is used and the level of activity is within the therapeutic range (international normalized ratio 2.5-3.0).18, 19 Some uncertainty exists about the management of patients using direct oral anticoagulants, but it is assumed that no interruption of therapy is required; consulting with the hematologist responsible for the patient's care is always advisable.20 Implant surgery in patients undergoing anticoagulation therapy has been reported in a number of controlled clinical studies, albeit consisting of rather small cohorts.21-24 Follow-up included an immediate postoperative period of 8-10 days. All the authors agreed that implants could be safely placed in patients with anticoagulation therapy without interruption of medication of vitamin K antagonists or direct oral anticoagulants. An exception to this may be dual anticoagulation therapy using two antiplatelet drugs (acetylsalicylic acid and clopidogrel), as is commonly employed following stenting of the coronary arteries. In these cases, postoperative morbidity may occur as a result of the increased risk of postoperative bleeding (Figure 1). Implant surgery should therefore be postponed until dual antiplatelet therapy has returned to single antiplatelet drug use. Depending on the type of stent used, this period may vary from 6 weeks to 6 months. To date, no information is available on implant complications arising in anticoagulated patients beyond the immediate period of surgical wound healing. The management of secondary interventions for soft tissue management or peri-implant diseases has not yet been reported on, but may have an impact on the long-term prognosis of implants, and should be taken into consideration when implants are planned for patients with anticoagulation management. Moreover, it should be noted that the necessity for anticoagulation therapy is commonly an underlying cardiovascular condition that needs to be explored and may require additional action. If anticoagulation therapy is used because of a cardiac condition associated with an increased risk for infective endocarditis, antibiotic prophylaxis is required.25 The necessity for antibiotic prophylaxis has been questioned based on a low risk of bacteremia during implant insertion,26 but adherence to current updates of national guidelines is strongly recommended.27, 28 Osteoporosis is characterized by a loss of structural quality of cancellous bone and a reduction in cortical bone thickness resulting in an overall deterioration of bone density. Approximately 48% of women and 15% of men aged ≥ 75 years are known to be affected.29 Primary osteoporosis can arise because of the loss of osteoanabolic effects of sex hormones (type I) in postmenopausal women (and some 10 years later in men), or because of age-related changes in general metabolism (type II). Osteoporosis may also arise secondary to endocrine diseases (eg, Cushing Syndrome, parathyroid hormone excess) or as a result of medication (eg, corticosteroids). Commonly, the diagnosis is derived from dual energy X-ray absorptiometry of the spine and/or the proximal femur. Dual energy X-ray absorptiometry scans provide a T-score that expresses the deviation of bone mineral density of the patient in standard deviations from the average value of healthy young adults. A T-score of < –2.5 is considered to be indicative of osteoporosis. Osteoporosis has been a concern in implant dentistry from an early stage in the development of the field.30-32 A number of papers have addressed the question of whether reduced skeletal bone density is associated with inferior bone quality in the maxilla or mandible. Subjectively, perceived jaw bone quality did not correlate with documented dual energy X-ray absorptiometry scores.33 Moreover, bone next to implants retrieved from osteoporotic patients did not exhibit a reduced number of bone cells or bone-to-implant contact.34 To identify individuals with reduced skeletal bone density, panoramic indices such as the mandibular cortex width,35 panoramic mandibular index,36 and the Klemetti index37 have been developed. A recent review reported these indices as useful in intercepting patients with reduced bone mineral density (T-score < 1), but did not recommend them to intercept patients with osteopenia/osteoporosis.38 Moreover, a systematic review examining the association between objective measures of jaw bone quality and skeletal bone mineral density was unable to clarify whether skeletal osteoporosis is associated with osteoporosis in the jaw bones.39 The role of osteoporosis in the success of implant treatment and the stability of marginal bone has been evaluated in a number of studies. Recent systematic reviews have found no difference in implant survival rates between patients with and without osteoporosis (risk ratio 1.9, 95% confidence interval 0.93-2.08, P = .11),40 or identified a direct but insignificant effect of osteoporosis on dental implant loss (risk ratio 1.09, 95% confidence interval 0.79-1.52).41 Similarly, earlier reviews and case control studies42-45 did not find evidence for an association between skeletal bone mineral density/osteoporosis and increased implant loss. With regard to peri-implant bone loss, the majority of recent studies (two cross-sectional,46, 47 one prospective,48 and one case control study49) reported no difference in radiographic peri-implant bone loss between patients with and without osteoporosis. Only one cross-sectional study reported significantly increased radiographic loss of marginal bone in osteoporotic patients after 1 year.50 All the patients in this study were part of a maintenance program with low periodontal indices and healthy periodontal conditions. Differences in radiographic bone level changes have been attributed to differences in bone remodeling in osteoporotic patients. The relevance of these findings with regard to long-term implant prognosis remains to be determined. While osteoporosis as such may not play a role in implant failure or loss of peri-implant bone, medications used for osteoporosis therapy may interfere with osseointegration and long-term maintenance of peri-implant health. The drugs prescribed are mostly either bisphosphonates51 or denosumab, a monoclonal antibody against the signaling molecule RANKL that is involved in the recruitment of osteoclasts. Bisphosphonates reduce both the resorptive activity of osteoclasts, as well as the activity of osteoblasts in a dose-dependent manner,52, 53 while denosumab directly reduces osteoclast activity.54 The net effect of the antiresorptive therapy is a decrease in bone turnover and remodeling activity of bone tissues. As remodeling is an essential part of bone regeneration and osseointegration, there has been some concern expressed regarding the capacity of peri-implant bone to incorporate implants inserted under bisphosphonate therapy. Controlled clinical trials have reported implant survival rates of 85.7%-100% in patients taking oral bisphosphonates55, 56 and of 100% for those receiving intravenous bisphosphonates.57 Recent meta-analyses of studies assessing the impact of bisphosphonates on implant treatment concluded that there is insufficient evidence for a negative effect of bisphosphonates on implant survival.58, 59 Besides the effect on implant survival, another aspect of the long-term use of antiresorptive agents is the risk of developing a medication-related necrosis of the jaw.60, 61 Medication-related necrosis of the jaw can be triggered by intra-oral surgical interventions and by bacterial invasion from odontogenic infectious lesions,62 as well as through pressure ulcers resulting from poorly fitting removable dentures.63 Triggering of the onset of medication-related necrosis of the jaw during the insertion of dental implants or through the occurrence of peri-implant infections during follow-up under antiresorptive medication is therefore a significant concern,64-66 and most often requires rather invasive measures for management (Figure 2A-G). The prevalence of medication-related necrosis of the jaw has been considered to depend in part on the route and frequency of bisphosphonate administration, with oral bisphosphonates presenting a lower risk for medication-related necrosis of the jaw than intravenous bisphosphonates. More recent reviews suggest that it is not the route of administration but the dosage of antiresorptive medication that affects the prevalence of medication-related necrosis of the jaw.59 The evidence reported for the occurrence of implant-related medication-related necrosis of the jaw under therapy with either bisphosphonates or denosumab is largely based on case reports64, 67-75 or retrospective case series.63, 76-84 In these reports, the number of cases reported for implant-related medication-related necrosis of the jaw in patients taking oral bisphosphonates is almost as high (n = 74) as in patients receiving intravenous bisphosphonates or denosumab (n = 84), suggesting that it is not the route of administration that is critical for the occurrence of implant-related medication-related necrosis of the jaw. Conversely, a number of case reports and case series reporting on implant treatment with concurrent oral bisphosphonate therapy did not find any cases of medication-related necrosis of the jaw in the patients studied.55, 65, 85-95 The existing level of evidence for an association between implant treatment and the occurrence of medication-related necrosis of the jaw under antiresorptive therapy remains low and needs to be substantiated by appropriately designed randomized controlled trials. Nevertheless, the overall number of reported cases of implant-associated medication-related necrosis of the jaw suggests that antiresorptive drugs need to be considered as a risk factor96 and explained to patients97 prior to the start of the treatment, as part of collecting informed consent. Despite the potential hazards of implant-associated medication-related necrosis of the jaw, implants can help to reduce the occurrence of medication-related necrosis of the jaw, for example, in edentulous patients under antiresorptive drugs by avoiding pressure ulcers resulting from poorly fitting dentures. Therefore, multiple factors need to be considered to inform a balanced decision on whether a patient with antiresorptive drugs is eligible for implant therapy (Table 2). If the majority of these factors indicate a low to moderate risk, implant therapy may also be a valid option in patients with antiresorptive medication. When oral surgical procedures are planned in patients with antiresorptive medication, antibiotic prophylaxis is recommended.98, 99 The ideal protocol for administration of antibiotics has not yet been defined. A clear recommendation is given for preoperative antibiotic coverage,100 however, the dosage and duration of postoperative continuation of antibiotic therapy remain to be determined. Adherence to national guidelines (if available) for the perioperative management of patients with antiresorptive medication is strongly advised. Diabetes mellitus is characterized by a lack of insulin secretion as a result of the loss of insulin-producing beta cells in the Langerhans islands of the pancreas (type 1) or by impaired insulin function because of the failure of insulin receptors to appropriately respond to the stimulation by insulin in the periphery (type 2). This results in constantly elevated blood glucose levels in people with diabetes, which leads to nonenzymatic glycation of numerous proteins to produce advanced glycation end products. An elevated level of advanced glycation end products leads to increased expression and activation of receptors for advanced glycation end products. These receptors are present on many cells (eg, endothelial cells, smooth muscle cells, fibroblasts, and mesanglial cells). Their activation mediates inflammatory reactions, which are considered to be responsible for alterations in the microvasculature and thereby can account for diabetic angiopathy.101 Interaction of advanced glycation end products with receptors for advanced glycation end products on macrophages is considered to be associated with macrophage dysfunction, leading to impaired wound healing in patients with diabetes.102 Moreover, bone regeneration is directly impaired on a molecular level in people with diabetes.103 Clinically, poor glycemic control has been shown to negatively affect the balance of bone growth factors in the peri-implant fluid during implant healing.104 Deterioration of vascularity in conjunction with a less efficient immunologic defense and a decreased regenerative capacity of peri-implant bone may compromise the success of implant treatment in patients with diabetes considerably. The effect of diabetes on implant success and the maintenance of peri-implant tissues has therefore been subject to research for more than 20 years. Numerous reviews have analyzed this relationship.105-115 A recent meta-analysis of 14 controlled clinical trials demonstrated that the risk ratio for implant loss between patients with and without diabetes was 1.07 (95% confidence interval 0.08-1.44), without a significant difference between the groups (P = .65).109 Failure to show an association between the existence of diabetes and an increased loss of dental implants is in line with previous reviews.20, 108, 113, 114, 116 The level of glycemic control as assessed by HbA1c appears to have no effect on implant survival rates, although patients with diabetes have demonstrated a compromised process of implant integration.104, 113, 117-119 Moreover, a recent consensus paper reported only inconclusive evidence for diabetes as a risk factor for peri-implantitis.5 While implant loss and peri-implant tissue health are obviously not affected by the presence of diabetes as such, management of the disease may play a role in the maintenance of peri-implant tissue health. A number of reports and systematic reviews have shown that patients with diabetes and poor glycemic control have an increased risk of peri-implantitis and associated peri-implant bone loss.76, 112, 120 This has been reported to become obvious at 2 years of follow-up compared with healthy individuals.107 However, when HbA1c is within the physiological range and oral hygiene is appropriate, the levels of inflammation have been shown to be reduced to those of healthy patients.121 The prophylactic use of antibiotics in oral surgical procedures in patients with diabetes is still controversial. Data from the scarcely available clinical studies favor the use of antibiotics but the evidence for their benefit is still low.122 The immune system is an indispensable part of tissue healing and repair. This holds true also for bone tissue, where pro-inflammatory cytokines are critical, not only for triggering regeneration but also for orchestrating subsequent bone remodeling.123 Moreover, both nonspecific and specific immune responses are crucial for the defense against bacterial invasion following surgery, as well as during the period of restoration and long-term usage. Immune deficiency can thus be critical for integration of dental implants and for the maintenance of peri-implant tissue health. Immune deficiency can result from a large number of conditions. With the exception of very rare innate immune defects, immune deficiencies are mostly acquired in nature. The nonspecific immune response can be affected by medications (immunosuppression/chemotherapy) and metabolic diseases (eg, diabetes mellitus), or because of chronic malnutrition. Specific immunity can also be reduced by immunosuppressive medication, as well as by hematological diseases and lymphotropic viruses (eg, HIV). Iatrogenic immunosuppression as a result of medications is probably the most frequent cause of immune deficiency in dental implant patients. A major indication for deliberate suppression of the immune response is organ transplantation. Organ transplant patients are treated with a combination of drugs that aim to reduce the proliferation of T-cells and to decrease the number of antigen-presenting cells to avoid rejection of the transplanted organ. Commonly, a combination of monoclonal antibody therapy, inhibitors of that and drugs with of is During the drug are high to immune after which are reduced for maintenance of interventions should not be planned during the of immune The effect of immunosuppression on the success of implant treatment in organ transplant patients has rarely been indicate that the peri-implant bone in a clinical information from a case series on patients with liver reported 100% success after Moreover, two prospective controlled studies found no significant difference in implant survival rates between organ transplant patients and after 1 and years of results without significant differences between groups have also been reported for clinical peri-implant soft tissue and for the of peri-implant The available evidence remains but suggests that the clinical results of implant treatment are and not significantly affected by immunosuppressive drugs used by organ transplant patients. of diseases in which immunosuppressive medication is used is the of diseases. The most for daily clinical are diseases, Syndrome, and disease, as well as conditions of oral and such as oral and systemic with oral or conditions that may largely cause local while such as or disease, may be of concern because of the systemic immunosuppressive medications immunosuppression in and in disease is by a combination of drugs, such as monoclonal against necrosis and drugs are a of agents that include and which are also used for immunosuppression in organ transplant diseases are characterized by and of clinical leading to a level of treatment during their This should be in when treatment for these patients. many patients have medication, the negative of this with regard to bone such as osteoporosis and decreased bone also be taken into osteoporosis is considered to be present at of ≥ These patients should be explored for receiving antiresorptive medication to avoid the There is very information available regarding patients with receiving dental implants. A retrospective evaluation of patients with an implant success of after The success rates but between patients with only and those with tissue diseases The stability of marginal bone by the medication drugs drugs and corticosteroids). The existence of tissue diseases was associated with a significant in peri-implant bone loss and higher bleeding indices compared with patients with an increased of peri-implant tissues to The of authors when examining a smaller cohort of patients with Moreover, a retrospective analysis of a cohort of patients did not identify as a significant risk factor for implant However, an of and systemic may these patients more to marginal peri-implant thus a maintenance The results available for patients with disease are Two cross-sectional analyses and one evaluation of cohorts of were by the examining early and implant loss and the role of implant the study one of the cross-sectional analyses identified a significant association between disease and implant the other cross-sectional study However, the of this is to as the number of patients in this cohort with disease was not diseases with oral Syndrome, systemic and oral in conjunction with dental implants, have largely been reported at an level for almost In and systemic were subject to early case reports years is considered to be critical for implant survival and not only as a result of medication, but more so because of leading to increased and bleeding as well as a higher frequency of As a result of the oral and patients with are often unable to removable and can benefit significantly from implant The level of evidence for the effect of on the success of implant treatment is Two case series and case reports provide into 17 patients with a of 99 implants, with 10 implants after years of Two recent retrospective cohort studies reported success rates of and soft tissues a higher but insignificant in the of patients with compared with healthy The existing thus suggests that implants in patients with are not significantly compromised by either the underlying disease or medication. The for peri-implant in these patients the elevated around in patients with Syndrome, and needs during is a disease associated with general of tissues resulting in reduced with subsequent with and dental has been reported in conjunction with dental implants on an level in individual and for two cases as

Background. Patients with epidermolysis bullosa (EB) have higher risk of developing infectious diseases. Its prevention requires timely vaccination. For now, there are no studies showing vaccination coverage for this category of children. Objective. Our aim was to study vaccination coverage of children with EB according to national preventive vaccination programmes. Methods. This retrospective cross-sectional study examined medical records of patients with EB from Russian Federation and neighbouring countries. Vaccination coverage (completeness and timeliness) and age of immunization initiation were analyzed. Moreover, we have studied the spectrum of early post-vaccine reactions and the course of the post-vaccine period in children with EB vaccinated for the first time. Results. The study included medical records of 134 patients with EB aged from 8 months to 17 years 8 months. Vaccination was performed according to national immunization programs in 37 (28%) children, only 21 cases were carried out in a timely manner. Medical exemptions were the major reason for the refusal of vaccination in most cases (82%). 48 patients with EB were vaccinated against 12 vaccine preventable diseases in the hospital. The post-vaccine period was asymptomatic in 36 (76%) patients, 10 (20%) patients had tenderness and hyperemia at the injection site, 2 (4%) patients had subfebrile fever. Conclusion. Most children with EB are still unvaccinated or vaccinated untimely. Immunization of such children against vaccine preventable disease according to the individual plan can be pretty useful.

There is limited evidence to suggest patients with epidermolysis bullosa (EB) have more postoperative wound complications than the general population. Despite this, the authors have noted reluctance among some surgeons to operate on these patients. A cross-sectional study was designed to investigate postoperative wound and scar healing outcomes in patients with EB. Patients were asked to complete the "Surgical Wound and Scar Healing in EB" questionnaire, and data gathered were analyzed. Forty-six patients completed the questionnaire for a total of 94 different surgical procedures. Five patients reported blistering at the surgical wound site. All 5 had generalized forms of EB. Four patients reported wound infections, and 1 patient reported wound dehiscence. The postoperative scar healed with keloid or hypertrophic scarring after 26% of the reported surgical procedures. Blistering at the postoperative site seems to be uncommon and particularly unlikely to occur in localized forms of EB. Postoperative wound infections and dehiscence are uncommon. Patients with EB may have a propensity to develop keloid or hypertrophic scarring. With these data, the authors hope clinicians have greater confidence in referring patients with EB for surgery, and surgeons more reassured about postoperative wound healing.

Objective To investigate the nursing care burden, medical assurance and comorbidities of patients with hereditary epidermolysis bullosa (EB) in China. Methods From September to December in 2018, a cross-sectional telephone/internet-based questionnaire survey was conducted in EB patients registered at DebRA China between January 2013 and September 2018. Results Totally, 377 participants (EB patients or their parents) were enrolled into this survey, and a total of 367 valid questionnaires were collected. Of the 367 registered patients with EB, 275 (74.9%) were minors, and 319 (92%) reported wound care costs per month less than 3 000 RMB Yuan, and 211 (57.5%) reported that medical expenses were mainly paid by themselves. These patients were distributed in 30 provinces, autonomous regions or municipalities directly under the central government of China, and no patient was from Tibet. The largest number of registered patients was from Jiangsu province (49/367) , followed by Henan (35/367) , Guangdong (27/367) , Hebei (23/367) and Shandong (20/367) provinces. Of the 367 patients, 168 received genetic testing. The most common comorbidities of EB patients were nail peeling and itching, with the prevalence rate being 66.2% and 55.3% respectively. Disabilities occurred in 122 (33.2%) patients, 102 (27.8%) of which had physical disabilities. Conclusion Most of EB patients cannot obtain appropriate diagnosis, nursing care and medical assurance, comorbidities and disabilities are common, and their quality of life is very low. Key words: Epidermolysis bullosa; Cross-sectional studies; Disabled person; Comorbidity