Otological complications in inversa type recessive dystrophic epidermolysis bullosa.

BACKGROUND: The rare inversa subtype of recessive dystrophic epidermolysis bullosa (RDEB-I) is characterized by predominant intertriginous skin blistering and marked mucosal involvement. Specific recessive missense mutations in the collagen VII triple helix are implicated in the disease. To date, otological complications have been reported infrequently in this patient group. METHODS: We conducted an observational, retrospective, double institution case record review of patients with RDEB-I who presented with otological complications between January 2000 and June 2020. Diagnosis was established on the basis of clinical features, family history and mutation analysis of the COL7A1 gene. RESULTS: In total, 11 (44%) of 25 patients with RDEB-I in our database (2 paediatric, 9 adult; mean age 40.9 years, range 8-72 years) experienced otological complications. Of these 11 patients, 10 (90.9%) had recurrent otitis externa, 7 (63.6%) had meatal stenosis and 7 (63.6%) had recurrent blistering of the external auditory canals. All 11 patients reported hearing difficulties, with conductive hearing loss confirmed by audiology testing in 6 (54.5%) of these. Of the 11 patients, 3 (27.3%) went on to have implantable hearing aids [2 bone-anchored hearing aids (BAHA) and 1 middle ear implant (MEI)] fitted with favourable outcome, while a fourth paediatric patient presented with a cholesteatoma that was surgically managed. DISCUSSION: We observed a higher prevalence of otological morbidity in RDEB-I than previously reported, and present the first case of cholesteatoma in epidermolysis bullosa (EB). Our data indicate that BAHA and MEI are safe and effective treatment options for hearing loss in EB. Clinicians should be vigilant in screening for ear symptoms in RDEB-I and consider early referral to an Ear, Nose and Throat specialist.

To what extent do disease severity and illness perceptions explain depression, anxiety and quality of life in hidradenitis suppurativa?

BACKGROUND: Hidradenitis suppurativa (HS) can have significant psychological consequences and affect quality of life (QoL). This has been associated with disease severity. However, it has not been established whether these effects are more strongly related to the severity of the disease, as rated by the clinician, or to the patient's perception of their condition. OBJECTIVES: To examine the relationships between disease severity and illness perceptions, and depression, anxiety and QoL in HS. METHODS: This study was cross-sectional in design. In total, 211 patients with HS completed the Brief Illness Perception Questionnaire (BIPQ), the Patient's Health Questionnaire-2 (PHQ-2), the Generalized Anxiety Disorder-2 (GAD-2) and the Dermatology Life Quality Index (DLQI). HS severity was assessed by the clinician, using the Hurley staging system. RESULTS: Patients with HS perceived their condition as chronic - having many symptoms, severe consequences and a negative emotional influence - and felt low personal control over their illness. Self-reports showed significant levels of depression, anxiety and impaired QoL, which were strongly associated with illness perceptions. Hierarchical regression analyses revealed that illness perceptions explained a much greater proportion of variance in depression, anxiety and QoL than the traditional explanatory variable, disease severity. CONCLUSIONS: HS can severely impair psychological well-being and QoL, which are more strongly associated with the person's beliefs about their illness than clinicians' severity assessments. Therefore, illness perceptions may be useful in the routine assessment of patients with HS and may provide a strong basis for interventions aimed at improving their psychological well-being and QoL.

Clinical features and WNT10A mutations in seven unrelated cases of Schöpf-Schulz-Passarge syndrome.

BACKGROUND: Schöpf-Schulz-Passarge syndrome (SSPS) is an autosomal recessive form of ectodermal dysplasia resulting from mutations in WNT10A. OBJECTIVES: To document the spectrum of clinical features and search for pathogenic mutations in seven unrelated cases of SSPS. METHODS: Clinical examination of patients and Sanger sequencing of genomic DNA spanning the coding exons and flanking spice sites of WNT10A. RESULTS: Most subjects had bilateral eyelid cysts and some degree of palmoplantar keratoderma, although nail, hair, and teeth abnormalities were variably present. Bi-allelic pathogenic mutations in WNT10A were found in all seven subjects. New mutations comprised p.Glu390*, p.Ser270Arg, and p.Cys362Arg; the recurrent mutations were p.Cys107* and p.Ala131Thr. CONCLUSIONS: This study reveals the range of ectodermal pathology in cases of SSPS that result from WNT10A mutations. Eyelid cysts provide a useful clinical clue to diagnosing SSPS which may be less rare than is currently appreciated.

Fibroblast cell therapy enhances initial healing in recessive dystrophic epidermolysis bullosa wounds: results of a randomized, vehicle-controlled trial.

BACKGROUND: Fibroblast cell therapy can modify disease biology in recessive dystrophic epidermolysis bullosa (RDEB) although whether it improves wound healing is not clear. OBJECTIVE: To assess the effects of injecting of allogeneic fibroblasts into the margins of chronic erosions in individuals with RDEB in a prospective, double-blind, randomized, vehicle-controlled phase II trial. METHODS: Erosions were randomized 1:1, to either a single treatment of 5 × 10(6) fibroblasts per linear cm of erosion margin or vehicle. All subjects continued standard wound care. The trial sponsor, participants and study outcome assessor were masked to treatment allocation. A hierarchy of endpoints germane to erosion closure was assessed. RESULTS: Twenty-six erosions in 11 subjects with RDEB were injected; 14 erosions received fibroblasts and 12 vehicle alone. A single series of injections was given at day 0 and all follow-up visits were completed. Treatment difference between fibroblasts and vehicle was -23.5% [95% confidence interval (CI) -3.5 to -43.5, P = 0.025] at day 7, -19.15% (95% CI 3.36 to -41.66, P = 0.089) at day 14 and -28.83% (95% CI 7.97 to -65.63, P = 0.11) at day 28. Beyond day 28, however, changes in mean erosion area did not differ significantly between the two groups. CONCLUSION: A single intradermal injection of allogeneic fibroblasts increases the initial rate of erosion healing in subjects with RDEB within the first 28 days but not thereafter. Further studies are needed to address the potential benefits of retreatment as well as optimal cell delivery.

A systematic review of the literature on the treatment of pityriasis rubra pilaris type 1 with TNF-antagonists.

BACKGROUND: Adult pityriasis rubra pilaris (PRP) type 1 is a rare chronic papulosquamous disorder with clinical and histological parallels with psoriasis. Treatment is challenging and recent case reports suggest a potential role for tumour necrosis factor (TNF) antagonists. OBJECTIVES: Our objective was to systematically review the literature for evidence of efficacy of TNF antagonists in the treatment of adult PRP. METHODS: We performed a systematic search of the Cochrane library, EMBASE, Pubmed and MEDLINE databases. We defined diagnosis of PRP, classified clinical response and whether this was clearly attributed to TNF-antagonists. We also reviewed disease, treatment duration and follow up. RESULTS: Sixteen articles were selected for detailed review. From these, 12 articles (13 cases) met our predefined criteria and were included in the systematic review. The authors identified two more cases from their personal archive. A total of 15 evaluable cases were included for analysis. Twelve showed complete response (CR) (80%) to TNF-antagonists with a mean time to maximal response of 5 months. In 10 of the CR cases (83%) this was clearly attributable to TNF antagonist therapy. CONCLUSION: These data indicate that TNF-antagonists may be of value in treating adult type 1 PRP refractory to other systemic agents but selective reporting bias, together with the lack of standard diagnostic criteria and established spontaneous resolution in PRP, prevent any firm recommendations on their place in management.

Desmosomal genodermatoses.

Desmosomes are intercellular junctions that contribute to cell-cell adhesion, signalling, development and differentiation in various tissues, including the skin. Composed of a network of transmembranous and intracellular plaque proteins, pathogenic autosomal dominant or recessive mutations have been reported in 10 different desmosomal genes, resulting in a spectrum of phenotypes variably affecting skin, hair and heart. This review summarizes the molecular pathology and phenotypes that predominantly affect the skin/hair. Recent desmosomal genodermatoses described include lethal congenital epidermolysis bullosa (plakoglobin), cardiomyopathy with alopecia and palmoplantar keratoderma (plakoglobin), hypotrichosis with scalp vesicles (desmocollin 3), and generalized peeling skin disease (corneodesmosin). Understanding the range of clinical phenotypes in combination with knowledge of the inherent desmosome gene mutation(s) is helpful in managing and counselling patients, as well as providing insight into the biological function of specific components of desmosomes in skin and other tissues.

Infliximab for the treatment of psoriasis in the U.K.: 9 years' experience of infusion reactions at a single centre.

BACKGROUND: Infliximab is an antitumour necrosis factor-α chimeric monoclonal antibody that is an established treatment for severe chronic plaque psoriasis. The recommended administration of a 2-h infusion followed by 2 h of monitoring is practised due to the potential occurrence of infusion reactions. However, accelerated infusions and shortened monitoring periods are used in patients with rheumatological disorders and inflammatory bowel disease without an increase in adverse events. OBJECTIVES: To review the standard infliximab infusion protocol, the incidence of acute infusion reactions, the use of concomitant methotrexate and the clinical relevance of the 2-h postinfusion monitoring period. METHODS: A retrospective case note and pharmacy database review of all infliximab infusions administered to patients with psoriasis at a tertiary dermatology centre was carried out. RESULTS: Fifty-nine consecutive patients received a total of 858 infliximab infusions (range 1-43 infusions per patient) between January 2001 and June 2010. The incidence of infusion reactions was 1.5%, affecting 16.9% of patients and occurring between the first and eleventh infusions. Mild, moderate and severe acute reactions occurred in 0.6% (n=5), 0.3% (n=3) and 0.3% (n=3) of infliximab infusions, respectively. Thirty-three patients (56%) received concomitant systemic treatments during part of or throughout the infliximab treatment, including 24 (41%) on methotrexate (5-20 mg weekly). The prevalence of infusion reactions in patients receiving infliximab alone was 27% compared with 4% in those receiving concomitant methotrexate (P=0.05). All infusion reactions were managed as per our trust protocol with only one infusion reaction occurring in the postinfusion period (10 min after infusion completion). CONCLUSION: The risk of infusion reactions in our cohort of patients was low, with the majority occurring early in the treatment cycle. Concomitant methotrexate may reduce this risk. A shortened postinfusion monitoring period can be safely considered.

Prevalence and treatment of vitamin K deficiency in paediatric patients with recessive dystrophic epidermolysis bullosa-severe subtype.

Introduction: Patients with recessive dystrophic epidermolysis bullosa-severe subtype (RDEB-S) are at risk of vitamin K deficiency, potentially causing abnormal clotting, excessive bleeding, poor bone metabolism and abnormal vascular calcification. This study quantifies vitamin K deficiency prevalence in this cohort and identifies potential risk-factors to prevent deficiency. Methods: Patients with RDEB-S who attended the EB service between 2014 and 2020 were included. Serum vitamin K and PIVKAII were measured as part of the usual nutritional blood screen. Dietetic and medical notes were reviewed to establish: antibiotic use, enteral feed intake and micronutrient supplementation. Results: A total of 16/25 64% (10/16 female), of children aged 22-180 months, had serum vitamin K and PIVKAII analysed. Six of sixteen (37.5%) patients had vitamin K deficiency requiring supplementation. Two of six (33.3%) normalized serum vitamin K after 12 weeks supplementation with oral menadiol diphosphate. Four of six (66.6%) await retesting following supplementation. Six of six (100%) patients with vitamin K deficiency were not consuming a gastrostomy/sip feed. Nine of ten (90%) patients with sufficient vitamin K levels were consuming either; more than 200 ml prescribed sip feed or more than 400-800 ml gastrostomy feed daily (containing 5.9-11 µg/100 ml vitamin K). Patients who were consuming either more than 200 ml prescribed sip feed or more than 400-800 ml gastrostomy feed daily (containing 5.9-11 µg/100 ml vitamin K) were significantly less likely to suffer from vitamin K deficiency (0.08 odds ratio [(1/7)/(5/3)] with significance level p = 0.0342 [95% CI: 0.0074-0.8275]). Sixteen of sixteen (100%) received antibiotics (range 0-4 courses/year; median, 3; IQR, 3). Patients with the most frequent antibiotics (n = 4) had normal vitamin K and PIVKAII levels if they consumed a minimum of 200 ml prescribed sip feed or 400-800 ml gastrostomy feed daily. Sixteen of sixteen (100%) patients took a multivitamin/mineral supplement; none contained vitamin K. Summary: The prevalence of vitamin K deficiency is 37.5% in this cohort. Patients whom were not consuming gastrostomy/sip feeds of at least 200 ml daily were at greatest risk of vitamin K deficiency. Patients on a micronutrient supplement remain at risk of vitamin K deficiency, as most contain no vitamin K. Prescribing a vitamin/mineral supplement that contains vitamin K is recommended. Twelve-week supplementation of oral vitamin K (5 mg/day for 1-10 years and 10 mg/day for 12-17 years) adequately improved stores.