Burden of itch in epidermolysis bullosa.

BACKGROUND: Itch is an unpleasant feeling that leads to scratching. It is a common, but understudied, problem in patients with epidermolysis bullosa (EB). OBJECTIVES: We measured the prevalence and characteristics of itch in the three major forms of EB: generalized EB simplex (EBS), junctional EB (JEB) and dystrophic EB (DEB). METHODS: Forty patients with EB were recruited from two tertiary care centres and one patient organization. The sample included 19 patients with EBS, seven with JEB and 14 with DEB. Patients completed the Leuven Itch Scale (LIS), a multidimensional self-report instrument that quantifies the frequency, duration, severity, distress, consequences and surface area of itch. This instrument has good clinimetric properties. RESULTS: Itch occurred in 85% of the patients, with substantial differences across the subtypes (EBS 74%, JEB 100%, DEB 93%). Itch, in all its dimensions, was most pronounced in patients with JEB and DEB, and less prominent in patients with EBS. The scores were significantly different for itch frequency, severity, distress and surface area, and the overall itch scores were comparable with those of atopic dermatitis. Itch mainly occurred in a hot environment (65%) and when sweating (62%). The most prevalent consequences were difficulty in falling asleep (88%) and lesions from scratching (85%). Differences between the three major subtypes were also observed in terms of circumstances, consequences and sensory characteristics. CONCLUSIONS: As expected, itch is common among patients with EB. All aspects of itch measured by the LIS were more severe in JEB and DEB than in EBS.

The needs of parents with children suffering from lethal epidermolysis bullosa.

BACKGROUND: Some subtypes of the heterogeneous genetic blistering disease epidermolysis bullosa (EB) lead to lethality in childhood. The severity and extent of blistering leaves these patients living in excruciating pain and distress their entire lives. Parents of these patients experience some specific problems, such as the unfamiliarity of EB amongst healthcare professionals and the suffering and loss of their child. OBJECTIVE: To identify the needs of parents who have lost their child to lethal EB. METHODS: A qualitative study was performed, comprising semistructured, in-depth interviews with 16 parents. The transcripts were analysed and common themes were identified. RESULTS: Parents indicated that they have the need (i) for a fast and correct referral to a specialized EB clinic, (ii) to be informed as honestly as possible about the diagnosis and lethal prognosis, (iii) to have a structured network of caregivers in the palliative care, (iv) to be involved in the care and the medical decisions involving their child, (v) to be informed about the end of life and to discuss euthanasia, (vi) for guidance and to have remembrances of their child, and (vii) for genetic counselling. CONCLUSIONS: Our job as healthcare professionals is to provide the best care not only for children suffering from lethal EB, but also for their parents. In this study, parents have provided us with some guidelines to care for them. However, it is important to keep in mind that every parent is different, and that the guidance should be tailored to their individual needs.

Long-term follow-up of patients with Herlitz-type junctional epidermolysis bullosa.

BACKGROUND: Junctional epidermolysis bullosa, type Herlitz (JEB-H) is a rare, autosomal recessive disease caused by absence of the epidermal basement membrane adhesion protein laminin-332. It is characterized by extensive and devastating blistering of the skin and mucous membranes, leading to death in early childhood. OBJECTIVES: To present the results of the long-term follow-up of a cohort of patients with JEB-H, and to provide guidelines for prognosis, treatment and care. METHODS: All patients with JEB-H included in the Dutch Epidermolysis Bullosa (EB) Registry between 1988 and 2011 were followed longitudinally by our EB team. Diagnosis was established using immunofluorescence antigen mapping, electron microscopy and DNA analysis. RESULTS: In total, we included 22 patients with JEB-H over a 23-year period. Their average age at death was 5.8 months (range 0.5-32.6 months). The causes of death were, in order of frequency: failure to thrive, respiratory failure, pneumonia, dehydration, anaemia, sepsis and euthanasia. The pattern of initial weight gain was a predictor of lifespan in these patients. Invasive treatments to extend life did not promote survival in our patients. CONCLUSIONS: It is important to diagnose JEB-H as soon as possible after birth so that the management can be shifted from life-saving to comfort care. The palliative end-of-life care can take place in hospital, but is also safe in the home setting. Suffering in patients with JEB-H can become so unbearable that in some patients who do not respond to adequate analgesic and sedative treatment, newborn euthanasia, performed according to the Groningen protocol, is legally permitted in the Netherlands.

Herlitz junctional epidermolysis bullosa: diagnostic features, mutational profile, incidence and population carrier frequency in the Netherlands.

BACKGROUND: Junctional epidermolysis bullosa, type Herlitz (JEB-H) is a lethal, autosomal recessive blistering disease caused by null mutations in the genes coding for the lamina lucida/densa adhesion protein laminin-332 (LAMB3, LAMA3 and LAMC2). OBJECTIVES: To present the diagnostic features and molecular analyses of all 22 patients with JEB-H in the Dutch Epidermolysis Bullosa Registry between 1988 and 2011, and to calculate the disease incidence and carrier frequency in the Netherlands. METHODS: All patients were analysed with immunofluorescence antigen mapping (IF), electron microscopy (EM) and molecular analysis. RESULTS: The mean lifespan of our patients with JEB-H was 5·8 months (range 0·5-32·6). IF showed absent (91%) or strongly reduced (9%) staining for laminin-332 with monoclonal antibody GB3. In EM the hemidesmosomes and sub-basal dense plates were hypoplastic or absent. We identified mutations in all 22 patients: in 19 we found LAMB3 mutations, in two LAMA3 mutations, and in one LAMC2 mutations. We found three novel splice site mutations in LAMB3: (i) c.29-2A>G resulting in an out-of-frame skip of exon 3 and a premature termination codon (PTC); (ii) c.1289-2_1296del10 leading to an out-of-frame skip of exon 12 and a PTC; and (iii) c.3228+1G>T leading to an exon 21 skip. CONCLUSIONS: All diagnostic tools should be evaluated to clarify the diagnosis of JEB-H. We have identified 11 different mutations in 22 patients with JEB-H, three of them novel. In the Netherlands the incidence rate of JEB-H is 4·0 per one million live births. The carrier frequency of a JEB-H mutation in the Dutch population is 1 in 249.

Junctional epidermolysis bullosa of late onset explained by mutations in COL17A1.

BACKGROUND: Junctional epidermolysis bullosa of late onset (JEB-lo) is a rare disease characterized by blistering of primarily the hands and feet starting in childhood. The pathogenesis remains unclear. OBJECTIVES: To clarify the pathogenesis of JEB-lo. METHODS: Two patients with JEB-lo, a brother and a sister, were examined using electron microscopy (EM), immunofluorescence (IF) antigen mapping and molecular analysis. RESULTS: We found subtle changes in IF antigen mapping and EM. The most remarkable changes were loss of the apical-lateral staining of monoclonal antibodies (mAbs) against type XVII collagen (Col17), and a broadened distribution of mAb staining against the ectodomain of Col17, laminin-332 and type VII collagen. Mutation analysis of COL17A1, encoding Col17, showed a compound heterozygosity for a novel mutation c.1992_1995delGGGT and the known mutation c.3908G>A in both patients. The deletion c.1992_1995delGGGT results in a premature termination codon and mRNA decay, leaving the patients functionally hemizygous for the missense mutation c.3908G>A (p.R1303Q) in the noncollagenous 4 domain of Col17. CONCLUSIONS: JEB-lo is an autosomal recessive disorder caused by mutations in COL17A1, and subtle aberrations in EM and IF antigen mapping are clues to diagnosis.