Liver Transplant in a Patient With Acquired Epidermolysis Bullosa and Associated End-Stage Liver Disease.

We report the first case of a liver transplant in a patient with epidermolysis bullosa acquisita and associated hepatitis B virus-hepatitis D virus cirrhosis and its inherent technical issues. Epidermolysis bullosa acquisita is an autoimmune multisystem disorder involving skin and mucosa characterized by the appearing of blisters and erosions. The more severe forms may result in nutritional compromise, anemia, osteopenia, dilated cardiomyopathy, laryngeal mucosal involvement, esophageal strictures, bladder, and kidney involvement requiring surgical intervention. Epidermolysis bullosa acquisita has become recognized as a multisystem disorder that poses several surgical challenges. This case shows that liver transplant is a feasible procedure in patients affected by epidermolysis bullosa acquisita. Patients with epidermolysis bullosa acquisita require a particular pretransplant assessment and a dedicated intra- and postoperative management of every invasive procedure that can traumatize the skin and mucosal epithelium to achieve an uneventful liver transplant. Epidermolysis bullosa acquisita does not represent a contraindication to liver transplant, and immunosuppression after transplant may favor a good systemic control of this immunologic disorder.

Early immunopathological diagnosis of ichthyosis with confetti in two sporadic cases with new mutations in keratin 10.

Ichthyosis with confetti (IC) is a severe non-syndromic ichthyosis due to heterozygous mutations in the KRT10 gene. The disease manifests at birth with erythroderma and scaling and is characterised by the gradual development of numerous confetti-like spots of normal skin. Diagnosis of IC is frequently delayed until adolescence or even adulthood. We report 2 young children who were first diagnosed as having congenital ichthyosiform erythroderma. However, the development of thick, confluent hyperkeratotic plaques together with the histopathological finding of keratinocyte vacuolisation in the suprabasal epidermis evoked IC. Immunofluorescence analysis showed a highly reduced keratin 10 expression within the cytoplasm of suprabasal keratinocytes and its characteristic mislocalisation to the nuclei. The diagnosis was confirmed by the identification of 2 previously unreported mutations in intron 6 and exon 7 of KRT10. Careful clinical examination then showed the presence of the first spots of normal skin in both patients at the age of 2.5 and 5 years, respectively. These cases point to the usefulness of immunofluorescence analysis of keratin 10 expression for an early diagnosis of IC.

A case of dystrophic epidermolysis bullosa improved with etanercept for concomitant psoriatic arthritis.

Epidermolysis bullosa is a group of inherited, chronic, non-inflammatory skin disorders, and dystrophic epidermolysis bullosa (DEB) is one of the most severe variants. The role of tumour necrosis factor alpha (TNFalpha) has not been reported in the pathogenesis of DEB. A DEB case is reported that appears to have responded well to the TNFalpha inhibitor etanercept given for the treatment of concomitant psoriatic arthritis. A progressive improvement in DEB was apparent over the first 3 months of treatment and persistent good control of DEB was noted over 3 years of therapy. A correlation between DEB improvement and etanercept has not been made, but the case may provide insight into the causal mechanisms of DEB.

Phacomatosis cesioflammea with unilateral lipohypoplasia.

Phacomatosis cesioflammea is characterized by the co-existence of a large nevus cesius (i.e., aberrant Mongolian spot, or nevus fuscocoeruleus) and an extensive nevus flammeus (i.e., port-wine stain). This sporadic genetic skin disorder represents a particular type of phacomatosis pigmentovascularis, a group of disorders that may reflect twin spotting. We report on a 28-year-old woman with aberrant Mongolian spots, bilateral melanosis bulbi, and systematized nevus flammeus partly intermingled with nevus anemicus. Moreover, pronounced lipohypoplasia of the right buttock and thigh as well as hypoplasia of the right breast are present. This anomaly of fatty tissue has not previously been reported in phacomatosis cesioflammea and further expands the clinical spectrum of this mosaic disorder. The patchy distribution of lipohypoplasia and its spatial relationship with vascular lesions strongly support the hypothesis of a postzygotic recombination event.

Laminin-5 mutational analysis in an Italian cohort of patients with junctional epidermolysis bullosa.

Junctional epidermolysis bullosa (JEB) is a rare genodermatosis characterized by dermal-epidermal separation that is caused by mutations in the genes encoding hemidesmosomal components and laminin-5, the major epithelial adhesion ligand. Here, we report on the mutational analysis of LAMA3, LAMB3, and LAMC2 genes encoding laminin-5 chains in 19 Italian patients, 11 affected with the severe Herlitz (H JEB) and eight with the mild non-Herlitz variant of JEB (non-H JEB). Eighteen mutations, seven of which were novel, were identified and their consequences analyzed at the mRNA and protein level. Premature termination codon mutations in both alleles of LAMB3 or LAMC2 genes were found in nine of the 11 H JEB patients, with a prevalence of mutations in LAMC2. In one case, a homozygous frameshift mutation in LAMB3 was associated to illegitimate splicing leading to non-H JEB. One H JEB patient showed a large intragenic duplication within LAMC2, a genetic defect so far uncovered in laminin-5 genes. Splicing or missense mutations, were prevalent in non-H JEB patients. Collectively, five mutations appeared to be frequent in laminin-5 JEB patients: R635X, 29insC, E210K, W143X in LAMB3 and R95X in LAMC2. These recurrent mutations account for approximately 44% of laminin-5 JEB alleles in Italian patients.

Annular lichenoid dermatitis of youth.

BACKGROUND: Lichenoid dermatoses are composed of a wide spectrum of disorders with a common histopathologic interface pattern but diverse causes and pathophysiology. OBJECTIVE: We describe a series of young patients with a peculiar annular lichenoid dermatitis, the clinical appearance of which initially suggested diagnoses of morphea, mycosis fungoides, or annular erythema. RESULTS: The study involved 23 patients (median age 10 years; age range 5-22 years). Lesions consisted of persistent asymptomatic erythematous macules and round annular patches with a red-brownish border and central hypopigmentation, mostly distributed on the groin and flanks. Histology revealed a peculiar lichenoid dermatitis with massive necrosis/apoptosis of the keratinocytes limited to the tips of rete ridges, in the absence of dermal sclerosis and epidermotropism of atypical lymphocytes. The infiltrate was composed mainly of memory CD4(+) CD30(-) T cells with few B cells and macrophages. Analysis of T-cell receptor-gamma-chain gene rearrangement in skin biopsy specimens revealed polyclonality in all the 15 cases studied. Topical and systemic corticosteroids or phototherapy were effective in most patients with relapse after treatment withdrawal. CONCLUSIONS: We suggest that this is a distinctive inflammatory condition, and we propose to term it "annular lichenoid dermatitis of youth."