Only comments seeking to improve the quality and accuracy of information on the Orphanet website are accepted. For all other comments, please send your remarks via contact us. Only comments written in English can be processed. Dystrophic epidermolysis bullosa DEB is a form of inherited epidermolysis bullosa EB characterized by cutaneous and mucosal fragility resulting in blisters and superficial ulcerations that develop below the lamina densa of the cutaneous basement membrane and that heal with significant scarring and milia formation.
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What you should be alert for in the history Inherited dystrophic epidermolysis bullosa DEB, including dominant [DDEB] and recessive [RDEB] subtypes should be considered in any patient with a history of blistering present at or shortly after the time of birth, especially if there is a family history of lifelong blistering in any family members.
DDEB patients almost always have a parent with similar or identical findings, since the rate of spontaneous mutation among DDEB patients is quite low. Characteristic findings on physical examination Continue Reading. DEB should be at the top of any differential diagnosis in those patients having marked mechanical fragility of the skin, blisters, a generalized distribution of other cutaneous findings, to include atrophic scarring, milia, nail dystrophy, and mucous membrane involvement.
Some of these typical cutaneous findings may not develop until an infant is at least several months old, making these findings by themselves insensitive surrogate markers of the disease in newborns and infants. There are several clinically distinctive subtypes of DEB, to include both generalized and more localized variants the latter to include acral, inverse, and centripetal distributions.
Figure 1. Figure 2. Figure 3. Figure 4. Figure 5. Expected results of diagnostic studies All forms of DEB are characterized by subepidermal blisters. Performance of routine histology is not recommended, since it may be difficult or impossible to accurately demonstrate the precise level of blister formation with this technique. The gold standards for diagnosis are antigenic immunofluorescence mapping, coupled with specific monoclonal antibody staining techniques and transmission electron microscopy, both performed on skin sampled from freshly induced blister sites.
The hallmark findings in RDEB are the presence of a sublamina densa cleavage plane, absence of type VII collagen staining along the dermoepidermal junction, and absence of detectable anchoring fibrils.
Although DDEB skin also cleaves beneath the lamina densa of the skin basement membrane, relative expression of type VII collagen and the number of mature-appearing anchoring fibrils can vary considerably, especially within skin specimens from patients with more localized variants of DDEB. There are no imaging or serologic tests for any form of inherited EB.
Mutational confirmation, however, is not needed in every patient, especially in those with classic phenotypic features and positive family history, until the availability and affordability of gene therapy necessitates its determination. It is important to stress, however, that there may be considerable variability in phenotypic expression even within the same affected kindred, and that in any given patient the genotype alone cannot be reliably used by itself as an accurate prediction of clinical severity and disease course.
Diagnosis confirmation With rare exceptions, there is no significant differential diagnosis for adults with DEB except in those with late ie, adulthood onset of disease manifestations , at which point the diagnosis of acquired EB should be entertained and excluded by direct and indirect immunofluorescence studies. In the setting of neonatal blistering, in the absence of a positive family history of DEB, the major differential diagnosis is neonatal herpes simplex infection.
Additional diagnostic considerations in infants with blisters may include congenital porphyria, bullous mastocytosis, bullous impetigo, staphylococcal scalded skin syndrome, bullous congenital ichthyosiform erythroderma, ichthyosis bullosa of Siemens, acrodermatitis enteropathica, and pachyonychia congenita. Who is at Risk for Developing this Disease? The overall prevalence and incidence of inherited EB in the United States has been recently reported to be There are no non-genetic risk factors for any form of inherited EB.
What is the Cause of the Disease? Although every possible type or combination of types of mutation s within this gene has been reported to result in DEB, in general the most severe subtype, known as generalized severe RDEB formerly named Hallopeau-Siemens RDEB is characterized by the presence of premature termination codons in both COL7A alleles.
The presence of COL7A mutations results in the production of variable amounts of mutated gene product. The absence of type VII collagen within the dermoepidermal junction is associated with a lack of anchoring fibrils, whereas the production of variable amounts of mutated type VII collagen leads to the presence of reduced amounts of mechanically unstable anchoring fibrils within the skin.
In each situation, the end result is marked mechanical fragility of the skin, recurrent blister formation, and scarring. There is also evidence of increased collagenolysis in the upper dermis of patients with generalized RDEB, further compromising the integrity of the dermoepidermal junction. Preliminary data suggest that modifying genes may play some role in the intrafamilial variability of clinical severity in patients with RDEB, especially in the relative expression of those genes involved in scarring.
Systemic Implications and Complications Patients with both major types of DEB, especially those with generalized RDEB, are at risk of developing a number of extracutaneous complications that impact on functionality and quality of life. Organ systems that may be involved include the oral cavity, gastrointestinal and genitourinary tracts, musculoskeletal system, external eye, heart, and bone marrow.
Some of these may develop within the first year of life, and most become increasingly prevalent with increasing age.
The most common manifestations in the oral cavity in DEB are painful blisters, erosions, and soft tissue scars. RDEB patients also are at risk for microstomia, ankyloglossia, excessive caries, loss of surface markings on the tongue, and early loss of dentition.
The external eye may develop blisters and scarring, which infrequently may lead to blindness. The most common complications within the gastrointestinal tract are progressive esophageal strictures or webs and severe constipation. Patients with severe generalized RDEB are at risk for recurrent urethral erosions and strictures, as well as hydroureter and chronic renal insufficiency, the latter associated with renal amyloidosis or poststreptococcal glomerulonephritis.
A subset of infants with severe generalized RDEB may develop dilated cardiomyopathy, possibly related to selenium or carnitine deficiency. Severe multifactorial anemia is one of the hallmarks of severe generalized RDEB, as is profound growth retardation, undoubtedly the result of chronic severe gastrointestinal disease activity, with loss of iron via intestinal bleeding, altered nutrient uptake by intestinal epithelium, and chronic systemic inflammation.
Severe depression is also common among patients with generalized forms of EB, especially those with RDEB, and may result in suicidal ideation or attempts. There is no decreased life expectancy in patients with DDEB. In contrast, a minority of children with generalized RDEB die within the first year of life, most often the result of sepsis or failure to thrive. Most patients with severe generalized RDEB, and to a lesser extent those with inverse or other subtypes of generalized EB, are at risk of death during adulthood, due to the development of eventually metastatic squamous cell carcinomas SCCs.
Other infrequent causes of death in adults with severe generalized RDEB are renal failure and progressive cardiomyopathy. These may very rarely arise as early as the middle of the first decade of life, although the earliest reports within the United States are at about age 12 or The cumulative risk of SCC does not begin to dramatically rise until the mid-third decade and beyond. Although each of these tumors is usually histologically well differentiated, the rates of local recurrence and regional and distant metastases are great.
These tumors are also resistant to chemotherapy and radiotherapy. At present there are no universally agreed-upon protocols for the surveillance for and workup of possible extracutaneous complications in patients with RDEB, although most EB experts suggest that baseline laboratory tests be conducted in early childhood to look for as yet clinically silent anemia and renal and cardiac disease.
Recent recommendations have been published, however, for evaluation and treatment of squamous cell carcinomas arising in the setting of DEB. Awareness of the usual time of onset for early involvement of one or more organs usually dictates the timing of rigorous clinical surveillance and the pursuit of more elaborate diagnostic tests, if signs and symptoms suggest their need.
For example, there is only rarely any justification for pursuing upper gastrointestinal tract radiograms or endoscopy in asymptomatic infants, whereas these would be appropriate in older children or adults if there are sufficient symptoms present to suggest that intervention with esophageal dilatation would be indicated, were significant stricture formation present. Treatment Options The mainstays of day-to-day care of any patient with inherited EB are prevention of trauma and infection of the skin, promotion of wound healing, and optimization of nutritional intake.
As yet there are no specific therapies for any type or subtype of inherited EB, although phase I clinical trials are now underway in DEB to explore the feasibility and possible benefits of ex vivo gene therapy transplantation of sheets of recombinant DNA corrected autologous keratinocytes, stem cell transplantation, and injections of allogeneic cells fibroblasts.
A recent phase I trial on injection of recombinant type VII collagen was halted due to safety concerns. A phase I trial of losartan in RDEB is underway to explore the possible benefit effect on a drug known to inhibit scar formation on modulation of cutaneous disease activity and, long-term, a possible positive impact on the risk of carcinogenesis in this patient population.
Nonadherent synthetic dressings ie, Mepitel; Mepilex; other are applied to open wounds to promote reepithelialization. These can then be changed daily or every few days and, if still partially adherent, can be easily soaked off with tap water.
Some authorities recommend prior application of a topical antibiotic ie, Polysporin; Silvadene to these wounds to reduce the risk of secondary infection. Potent topical antimicrobials ie, Bactroban are usually not for routine day to day care, since chronic use in EB patients may lead to superinfection with methicillin resistant Staphylococcus aureus MRSA. Some authorities also routinely use silver-impregnated dressings, although some concerns have been raised about the potential for excessive absorption of silver into the bloodstream from those dressings.
Esophageal strictures may be at least temporarily improved by serial dilatation, performed by either a gastroenterologist or a pediatric surgeon experienced in the management of children with recessive dystrophic EB.
A variety of oral medications, to include lactulose, may be used in patients with moderate to severe constipation. Patients with recurrent ocular erosions or scars should be referred to an ophthalmologist for optimal care. Aggressive nutritional support should be employed in any child with recessive dystrophic EB who has evidence of growth retardation, since malnutrition oftentimes arises in these patients as a result of chronic loss of blood and protein through nonhealing wounds on the skin and within the gut.
Surgical Patients with progressive webbing of the fingers should be referred to a hand surgeon experienced in the management of these complications, since degloving and separation of these webs may lead to temporary functional improvement. Unfortunately, these hand deformities frequently recur, requiring repeated surgical intervention to maintain optimal functionality.
Similar pseudosyndactyly arising on the feet rarely require intervention, since they tend not to interfere significantly with ambulation. Individuals with severe esophageal strictures who cannot be treated by dilatation may require transcolonic interposition. Biopsy-proven squamous carcinomas need wide excision to ensure clear margins. In general I prefer to have these done by a surgical oncologist. Although there are robust data supporting the use of MOHS surgical technique for the treatment of SCCs in non-EB patients, so as to minimize unnecessary removal of uninvolved skin, there are no similar data that would convincingly argue that this is also true in the setting of inherited EB.
Rare patients with regional metastases of their SCCs may briefly benefit from surgical debulking of these tumors, particularly if they are painful, nonhealing, malodorous, and otherwise impairing movement of the limb. It is possible to treat nonhealing ulcerations of the skin with split-thickness skin grafts once it is proven by biopsy that those wounds do not instead represent SCC. Urologic complications are uncommon in dystrophic EB. Any suggestion of their presence, however, merits evaluation by a urologist.
Similarly, there are no published chemotherapeutic regimens that appear to be efficacious in the setting of RDEB. Optimal Therapeutic Approach for this Disease As noted above, the primary focus of dermatologic care in patients with RDEB revolves around the prevention and treatment of wounds. If any is seen, then the patient should be referred to an appropriate specialist for further evaluation and care.
As discussed elsewhere, priorities in surveillance should be based upon knowledge of the time during which each of the major extracutaneous complications usually first arise. Recommendations regarding the latter may be found in a recently published review article on this subject.
Patient Management Patients with dystrophic EB need close follow-up by both a dermatologist and a primary care physician.
During the first few years of life, EB children may need to be seen as frequently as every 1 to 2 months, until their parents are sufficiently comfortable enough about routine wound care that they can bring their children in for follow-up on a less frequent basis. Close collaboration with a pediatrician familiar with EB will be critical during infancy and early childhood, since it is likely that children with dystrophic EB may develop other illnesses unrelated to their underlying skin disease.
Several of the more severe extracutaneous manifestations of generalized EB, most notably external eye erosions and tracheolaryngeal and esophageal strictures, may begin as early as the first year of life. Identification of and intervention in these at an early stage may prevent more serious complications during later childhood or young adulthood.
A more detailed discussion of the breadth and relative frequency of extracutaneous complications may be found in a recent review article. Although SCCs have been reported as early as the middle of the first decade of life in rare children with severe generalized RDEB, these tumors usually do not first develop until early adolescence. The cumulative risk of a RDEB patient developing at least one squamous carcinoma, however, rises rapidly as he or she approaches the third and fourth decades of life.
Furthermore, any lesion in which a differential diagnosis of SCC is being entertained should be biopsied immediately rather than instead being observed serially, since SCCs arising in individuals with RDEB often present as otherwise nondescript nonhealing erosions rather than as the more prototypic scaly nodules that arise in adults who lack EB.
Close monitoring of weight and height will be important in children with RDEB, since marked growth retardation and often severe multifactorial anemia are common complications. A nutritionist experienced in managing EB children should be involved in their multidisciplinary care. Elective gastrostomy may be particularly helpful in children who are unable to correct their nutritional deficiencies by oral means. Suicidal ideation has been documented in some cohorts of patients, emphasizing the need for psychiatric assistance with any EB patient having such complaints.
Similarly, parents and unaffected siblings may also need psychological and psychiatric support, given the incredible burden that a child with RDEB places on the family unit. Assistance by physical therapy, vocational therapy, and social work may also be important in the overall management of the patient with inherited EB.
Epidermolysis bullosa dystrophica
Alternative titles; symbols. Other entities represented in this entry:. Autosomal recessive dystrophic epidermolysis bullosa is a severe skin disorder beginning at birth and characterized by recurrent blistering at the level of the sublamina densa beneath the cutaneous basement membrane. This results in mutilating scarring and contractures of the hands, feet, and joints.
Dystrophic Epidermolysis Bullosa (EB hereditaria dystrophica)
Dystrophic epidermolysis bullosa is one of the major forms of a group of conditions called epidermolysis bullosa. Epidermolysis bullosa cause the skin to be very fragile and to blister easily. Blisters and skin erosions form in response to minor injury or friction, such as rubbing or scratching. The signs and symptoms of dystrophic epidermolysis bullosa vary widely among affected individuals. In mild cases, blistering may primarily affect the hands, feet, knees, and elbows. Severe cases of this condition involve widespread blistering that can lead to vision loss, scarring, and other serious medical problems. Researchers classify dystrophic epidermolysis bullosa into major types based on the inheritance pattern and features of the condition.
Dystrophic epidermolysis bullosa
DermNet provides Google Translate, a free machine translation service. Note that this may not provide an exact translation in all languages. Epidermolysis bullosa EB is a group of inherited diseases that are characterised by blistering lesions on the skin and mucous membranes. These may occur anywhere on the body but most commonly appear at sites of friction and minor trauma such as the feet and hands. In some subtypes, blisters may also occur on internal organs, such as the oesophagus , stomach and respiratory tract, without any apparent friction.
What you should be alert for in the history Inherited dystrophic epidermolysis bullosa DEB, including dominant [DDEB] and recessive [RDEB] subtypes should be considered in any patient with a history of blistering present at or shortly after the time of birth, especially if there is a family history of lifelong blistering in any family members. DDEB patients almost always have a parent with similar or identical findings, since the rate of spontaneous mutation among DDEB patients is quite low. Characteristic findings on physical examination Continue Reading. DEB should be at the top of any differential diagnosis in those patients having marked mechanical fragility of the skin, blisters, a generalized distribution of other cutaneous findings, to include atrophic scarring, milia, nail dystrophy, and mucous membrane involvement. Some of these typical cutaneous findings may not develop until an infant is at least several months old, making these findings by themselves insensitive surrogate markers of the disease in newborns and infants. There are several clinically distinctive subtypes of DEB, to include both generalized and more localized variants the latter to include acral, inverse, and centripetal distributions. Figure 1.
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