Andrew N. Lin

Revised clinical and laboratory criteria for subtypes of inherited epidermolysis bullosa: A consensus report by the Subcommittee on Diagnosis and Classification of the National Epidermolysis Bullosa Registry

Inherited epidermolysis bullosa encompasses a number of diseases, with the common finding of blister formation after minor mechanical trauma to the skin. In some forms significant, if not eventually fatal, extracutaneous disease activity may occur. In recent years application of newer technologies has contributed substantially to an overall understanding of this collection of inherited diseases. Concurrently, many new phenotypes have been recognized, in part the result of ongoing prospective patient registries in the United States and abroad. Unfortunately, this has resulted in a massive literature that may appear to be confounded by seemingly excessive or arbitrary subdivision of epidermolysis bullosa variants. With these concerns in mind a subcommittee was established by the National Epidermolysis Bullosa Registry to summarize the current literature and to make recommendations as to the best clinical and laboratory criteria for the practical diagnosis and subclassification of patients with inherited epidermolysis bullosa.

Treatment of junctional epidermolysis bullosa with epidermal autografts

We have successfully treated chronic facial erosions in three boys with junctional epidermolysis bullosa. In each patient, keratinocytes were harvested from the roof of suction blisters created on clinically uninvolved skin. They were grown in tissue culture on collagen sponges and grafted onto facial erosions that were previously treated with 2% mupirocin ointment. This experimental antibiotic ointment has proved efficacy in eradicating cutaneous pathogens such as Staphylococcus aureus from chronic wounds. In two patients, complete reepithelialization was achieved over 7 and 10 months, respectively, and partial reepithelialization occurred in another patient in whom treatment is ongoing. Epidermal autografts are a promising means for improving function and appearance in eroded skin caused by junctional epidermolysis bullosa.

Mupirocin-resistant Staphylococcus aureus after long-term treatment of patients with epidermolysis bullosa

In a long-term, open study, 47 patients with epidermolysis bullosa were treated with topical 2% mupirocin (Bactroban) ointment to decrease bacterial infection and promote wound healing. This antibiotic is effective against gram-positive but not gram-negative organisms. No significant adverse effects were noted, although some patients have been treated for more than 4 years. We sought evidence in this patient population for the appearance of bacterial strains with decreased sensitivity to mupirocin. In five patients cultures from nonhealing wounds revealed Staphylococcus aureus resistance to mupirocin. Four of these patients were given oral antibiotics to which S. aureus was sensitive; they improved clinically, and cultures of their wounds became negative for pathogens.

Lack of Efficacy of Phenytoin in Recessive Dystrophic Epidermolysis Bullosa

BACKGROUND Recessive dystrophic epidermolysis bullosa is an uncommon, severely disabling, heritable disorder characterized by abnormal fragility of the skin. Open trials have suggested that phenytoin is an effective treatment, and this therapy is now widely used. METHODS To determine the efficacy of phenytoin in the treatment of recessive dystrophic epidermolysis bullosa, we performed a randomized, double-blind, placebo-controlled, crossover trial in 36 patients. Each treatment was given for five to seven months, separated by a two-month period. We measured the total number of blisters and erosions on the entire body, the size of three plaques containing blisters and erosions, and the number of blisters and erosions in the three plaques at the beginning and end of each treatment period in each patient. RESULTS Twenty-two patients completed both courses of therapy, seven patients completed one course, and seven patients withdrew before completing a single course. There was no significant difference in disease activity between phenytoin treatment and placebo treatment, as measured by changes in the number of blisters and erosions on the entire body (7 percent decrease vs. 6 percent increase), in the area of three designated plaques (0.4 percent decrease vs. 0.2 percent increase), or in the number of blisters and erosions in the designated plaques (12 percent decrease vs. 31 percent increase). CONCLUSIONS Phenytoin is not an effective treatment for patients with recessive dystrophic epidermolysis bullosa.

GASTROINTESTINAL MANIFESTATIONS OF EPIDERMOLYSIS BULLOSA : A STUDY OF 101 PATIENTS

One hundred one patients with EB were evaluated by a combination of prospective and retrospective review, and analyzed regarding the nature, incidence, and prevalence of their gastrointestinal (GI) manifestations. Involvement of the GI tract is a well-known extracutaneous manifestation of dystrophic EB, but it also occurred in more than one-half and one-third, respectively, of those with junctional and simplex EB. Most of the serious consequences, such as esophageal strictures and microstomia, occurred in recessive dystrophic EB but were also seen, although infrequently, in the junctional and simplex forms. The majority of patients with dysphagia had an esophageal stricture, and the cervical esophagus was the most common location. The onset of dysphagia generally occurred in the first decade of life, in patients much younger than previously recognized. Diagnostic endoscopy did not reveal lesions which could not have been detected radiographically. Lower GI complaints were common, especially constipation and perianal blistering, and affected all types of EB. These complaints contributed substantially to management problems but they did not correlate with colonic pathology and appeared to reflect anal or perianal disease.

Review of Ophthalmic Findings in 204 Patients With Epidermolysis Bullosa

Surgical excision of subfoveal neovascular membranes may result in recovery of excellent visual acuity in patients with presumed ocular histoplasmosis but not in patients with age-related macular degeneration. To provide an explanation for this discrepancy, I analyzed the clinical and histopathologic findings in five patients with presumed ocular histoplasmosis. These findings provide evidence that the new vessels arising in the choroid in these patients usually grow within the subsensory retinal space and not in the subpigment epithelial space, as occurs in patients with age-related macular degeneration. In presumed ocular histoplasmosis, the new vessels are partly engulfed by a monolayer of proliferating retinal pigment epithelium. Surgical excision of this membrane permits reapproximation of the retinal receptors and native pigment epithelium and may be associated with remarkable return of visual acuity.

Anesthetic management in epidermolysis bullosa: Review of 129 anesthetic episodes in 32 patients

BACKGROUND Anesthetic and monitoring instrumentations such as endotracheal intubation may cause skin and mucosal damage with potentially serious consequences in patients with epidermolysis bullosa (EB). OBJECTIVE This study defines the risks of skin and mucosal damage from anesthetic and monitoring techniques in patients with EB and formulates management guidelines. METHODS We retrospectively analyzed the outcome of 129 anesthetic episodes in 32 patients with various types of EB. RESULTS Serious complications did not occur in any patient with EB from the use of endotracheal intubation, face mask, nerve blocks, local anesthetics, and intravenous or intramuscular anesthetic agents. CONCLUSION With appropriate precautions, patients with EB can undergo standard anesthetic techniques with only minor and infrequent complications.

Junctional Epidermolysis Bullosa of the Larynx Report of a Case and Literature Review

Epidermolysis bullosa (EB) is a group of rare inherited disorders in which minor trauma causes blister formation in the skin and mucosa, including the esophagus. Morbidity varies with the type of disease and ranges from occasional trivial skin blisters to death in infancy. Laryngeal involvement presenting as hoarseness and respiratory distress has been reported in nine patients, five of whom had junctional EB. We present the sixth case of junctional EB with laryngeal involvement, and offer guidelines for otolaryngologists and anesthesiologists caring for these fragile patients.

Dystrophic epidermolysis bullosa inversa: Report of two cases with further correlation between electron microscopic and immunofluorescence studies

Dystrophic epidermolysis bullosa inversa is a rare form of epidermolysis bullosa characterized by blister formation in flexural skin areas and by marked oral and esophageal involvement. Recognition of this subset of dystrophic epidermolysis bullosa is important, because its prognosis differs from all other forms of dystrophic epidermolysis bullosa. Investigators recently reported normal staining with antibodies directed against type VII collagen in 14 patients, but electron microscopy in eight patients showed diminished or absent anchoring fibrils. We report here the cases of two additional patients with dystrophic epidermolysis bullosa inversa. One patient had finger web space scarring that required surgical correction and mild syndactyly of toes. Both patients had normal staining with LH 7:2, but electron microscopy showed diminished and rudimentary anchoring fibrils. These findings support the possibility that dystrophic epidermolysis bullosa inversa may be caused by a structural abnormality of type VII collagen that prevents proper assembly of collagen into distinct anchoring fibrils.

Junctional Epidermolysis Bullosa: A Clinical Overview

Junctional epidermolysis bullosa is an autosomal recessive disorder characterized by the formation of blisters at the lamina lucida, an electron-lucent zone located between the basal cell plasma membrane and the lamina densa (Fig. 8.1). Like other forms of epidermolysis bullosa (EB), several subtypes are recognized (Table 8.1). These are differentiated mainly on the basis of clinical manifestations, and it is unclear if they represent varying expressivity of a single defective gene, or diseases caused by abnormalities at different genetic loci. Staining with monoclonal antibodies directed at various basement membrane zone antigens is useful in characterizing certain forms of junctional EB,1 and this is topic is discussed in detail in Chapter 3. Abnormalities of hemidesmosomes have been observed in skin biopsy specimens from patients with junctional EB, especially those with the “letalis” form.2 Reduced numbers of morphologically ill-defined “hemidesmosomelike structures” have been observed in cultured keratinocytes obtained from junctional EB patients.3 In another study, cultured keratinocytes obtained from three patients with a nonletalis type of junctional EB showed altered structural, adhesive, and functional abnormalities.4 Compared with normal keratinocytes, junctional EB cells showed elongated refractile appearance, diminished cell-stratum adhesion, and were slow growing.4 A condition similar to junctional EB has been described in the toy poodle.5