Wing Yan Yuen

Risk of squamous cell carcinoma in junctional epidermolysis bullosa, non-Herlitz type: Report of 7 cases and a review of the literature

BACKGROUND Squamous cell carcinoma (SCC) is the most severe complication and most common cause of death in patients with recessive dystrophic epidermolysis bullosa. The risk of developing SCC among patients with junctional epidermolysis bullosa (JEB) is unclear from the literature; however, in our center we noticed an unexpected number of SCCs among adult patients with JEB. OBJECTIVE To review all documented patients with JEB in whom an SCC developed, both from our epidermolysis bullosa (EB) center and those reported in the literature. METHODS A search in our EB registry documenting all JEB patients visiting our EB referral center from 1990 through 2010 revealed 7 JEB patients who developed 1 or more SCCs. A systematic literature search revealed 8 relevant articles documenting a total of 7 patients who developed an SCC. RESULTS In our EB registry we found 7 patients with JEB who developed an SCC; these were all adults classified with non-Herlitz type JEB. The frequency of developing an SCC among adult JEB patients (n = 28) in our center was therefore 25%. In the literature, we found 7 case reports of JEB complicated by SCC (also classified as JEB, non-Herlitz type), bringing the total number of documented cases to 14. The first SCC in JEB patients developed at an average age of 50 years (median, 52 years; range, 28-70 years). In 9 of 14 cases, multiple primary SCCs occurred, with a total of 45 SCCs. The SCCs are most often located on the lower extremities, in areas of chronic blistering, long-standing erosions, or atrophic scarring. Three patients (21%) developed metastases and died on average 8.9 years after diagnosis of the initial SCC. LIMITATIONS This study was retrospective and the statistical analyses were based on a small number of patients. CONCLUSIONS From their third decade, adult patients with JEB have an increased risk (1:4) of developing SCC on their lower extremities. The SCCs have a high recurrence rate and follow an aggressive course that results in death in 1 of 5 patients. We recommend annual checks of all JEB patients for SCC starting at 25 years of age.

Enamel Defects in Carriers of a Novel LAMA3 Mutation Underlying Epidermolysis Bullosa

© 2012 The Authors. doi: 10.2340/00015555-1341 Journal Compilation

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.

Burden of itch in epidermolysis bullosa.

Itch is an unpleasant feeling that leads to scratching. It is a common, but understudied, problem in patients with epidermolysis bullosa (EB).

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.

ITGB4-associated non-Herlitz junctional epidermolysis bullosa: report of two new cases carrying two novel ITGB4 mutations

the nonrecurrence group and 80% (4 ⁄5) of the recurrence group (Table 2). Compared with the nonrecurrence group, the recurrence group was younger, with a higher proportion also suffering from cholinergic urticaria and showing lymphocyte infiltration of the sweat glands. The duration from onset to treatment was longer, and these patients were resistant to steroid therapy. However, no statistically significant differences were identified. In general, continued anhidrosis over a long period results in abnormalities of the sweat glands and postganglionic sudomotor nerves. Treatment therefore requires long-term administration of high-dose steroids. In our patients, the duration from onset to treatment was longer for the recurrence group than for the nonrecurrence group. This suggests that changes to the sweat glands and postganglionic sudomotor nerves would have been more pronounced in the recurrence group than in the nonrecurrence group, with the possibility of steroid resistance. These changes might also mean that negative feedback from acetylcholine release by nerve terminals did not come into effect, leading to excessive release of acetylcholine by nerve terminals. We theorize that this was the reason for the higher frequency of the complication of cholinergic urticaria among patients who experienced recurrence. We also administered immunosuppressants to patients who experienced recurrent anhidrosis, but these proved ineffective. Oral ciclosporin has previously been reported as effective for treating intractable AIGA. This was attributed to the fact that ciclosporin inhibits the activity of CD3and CD4-positive T cells that infiltrate eccrine sweat glands, causing sweating. Ciclosporin was probably ineffective in our patients because lymphocyte infiltration of eccrine sweat glands was either absent or mild. Treatment of AIGA using methods other than immunosuppressants and steroid therapy has not previously been reported. Novel treatments for AIGA are thus desired. Treatment for AIGA is not consistently effective, and much remains unclear regarding the reasons for recurrent anhidrosis. Elucidation of the reasons underlying the recurrence of anhidrosis will also be important for clarifying the pathogenic mechanisms of AIGA. We believe that accumulation of more cases and further study of courses of treatment are required.

Health-related Quality of Life in Epidermolysis Bullosa: Validation of the Dutch QOLEB Questionnaire and Assessment in the Dutch Population

Defining the health-related quality of life (HRQoL) in patients suffering from the heritable blistering disease epidermolysis bullosa (EB) is important in assessing the efficacy of new treatments. The quality of life in EB questionnaire (QOLEB) is an English 17-item EB-specific HRQoL measurement tool. The aim of this study was to develop a validated and reliable QOLEB in Dutch and assess the HRQoL in Dutch EB patients. The QOLEB was translated to Dutch according to protocol. Fifty-five adult patients across 4 EB subtypes participated. The QOLEB had excellant correlation with the Skindex-29 (ρs = 0.86), good correlation with the SF-36 physical score (ρs = -0.75), and moderate correlation with the SF-36 mental score (ρs = -0.43). The discriminative validity between the 4 different EB subtypes was significant (p = 0.002). The internal consistency was excellent (α = 0.905), and the test-retest reliability strong (ρs = 0.88). In conclusion, the Dutch QOLEB is a reliable and valid instrument for the assessment of the HRQoL in adult EB patients.

Fullerene C60 with cytoprotective and cytotoxic potential: prospects as a novel treatment agent in Dermatology?

It is known that an excess amount of (oxygen) radicals in the skin can lead to (local cellular) oxidative stress. From one side, oxidative stress can contribute to the existence of various (inflammatory) skin diseases such as acne vulgaris and alopecia, as well as to accelerated photo‐ageing of the skin. From the other side, oxidative stress could also be a wanted process for curing particular skin diseases, such as skin cancer and microbial skin infections. Therefore, novel treatment agents with the ability to scavenge or generate radicals can potentially be meaningful in the treatment of various skin diseases, especially for those diseases that have limited effective treatment options. This viewpoint essay will discuss the potential of fullerene C60, i.e. buckminsterfullerene, derivatives as novel treatment agents in dermatology. Fullerene C60 is an all carbon molecule with a unique dual ability; fullerene C60 can act as a radical scavenger or as an oxygen radical generator. Hence, fullerene C60 derivatives offers most interesting prospects as a therapeutic protective or therapeutic toxic agent. Because of their extraordinary physicochemical properties and numerous chemical functionalization possibilities, chemists can design derivatives with a wide scope of unique properties. The experimental data, mostly from in vitro and in vivo animal studies, on the safety and therapeutic potential of fullerene C60 derivatives, in the field of dermatology will be discussed.

Carriers with functional null mutations in LAMA3 have localized enamel abnormalities due to haploinsufficiency

The hereditary blistering disease junctional epidermolysis bullosa (JEB) is always accompanied by structural enamel abnormalities of primary and secondary dentition, characterized as amelogenesis imperfecta. Autosomal recessive mutations in LAMA3, LAMB3 and LAMC2 encoding the heterotrimer laminin 332 (LM-332) are among the genes causing JEB. While examining pedigrees of JEB patients with LAMA3 mutations, we observed that heterozygous carriers of functional null mutations displayed subtle enamel pitting in the absence of skin fragility or other JEB symptoms. Here, we report two new LAMA3 functional null mutations: nonsense c.2377C>T p.(Arg793Ter) and splice-site c.4684+1G>A mutation in heterozygous carriers exhibiting enamel pitting. Both parents had offspring affected with JEB and displayed subtle enamel pitting of secondary dentition without any sign of skin blistering. The reported enamel abnormality in LAMA3 mutation carriers could be attributed to a half dose effect of the laminin α3 chain (haploinsufficiency).

The Pain Quality Assessment Scale for epidermolysis bullosa

Pain is one of the most debilitating symptoms in epidermolysis bullosa (EB) leading to reduced quality of life. Pain in EB comprises both neuropathic and non-neuropathic qualities. An assessment of pain qualities has not formerly been completed in EB. The Pain Quality Assessment Scale (PQAS) is an adjusted version of the validated Neuropathic Pain Scale and includes 20 pain qualities and descriptors. Patients with EB (n = 43) rated the pain qualities in the PQAS on 20 numerical scales and 1 multiple choice question. Pain was experienced by 39 patients (91%). In general, patients with EB experience intense and unpleasant pain on the surface of the skin; the hands and feet are most commonly affected. The subtypes, recessive dystrophic EB and junctional EB reported pain qualities pathognomonic of neuropathic pain. The PQAS adds value to the current practice of global pain intensity scoring in EB.