Keratolysis exfoliativa (dyshidrosis lamellosa sicca): a distinct peeling entity.

BACKGROUND: Keratolysis exfoliativa (KE), also known as dyshidrosis lamellosa sicca, is a palmoplantar dermatosis characterized by air-filled blisters and collarette desquamation. It has been regarded as a subtype of dyshidrotic eczema, a fungal infection or a dermatophytid reaction. KE may also resemble acral peeling skin syndrome and localized epidermolysis bullosa simplex. Although KE is a common disorder, it is a rarely reported and is an under-recognized dermatosis. OBJECTIVES: To delineate the characteristic features of KE. METHODS: We investigated the clinical, immunohistopathological, ultrastructural and molecular features of KE. Patients were included from the clinical records. Additional diagnostic research consisted of mutation analysis of the candidate genes TGM5, KRT5, KRT14, FLG, SPINK6 and SPINK9. RESULTS: A total of 24 patients with KE were identified, six with familial and 18 with sporadic KE. Lesions consisted of air-filled blisters only on palmoplantar skin, followed by collarette and lamellar peeling. Both light microscopy and electron microscopy showed cleavage and partially degraded corneodesmosomes within the stratum corneum, whereas immunofluorescence microscopy showed normal expression of corneodesmosomal components. No mutations were found in TGM5, KRT5/14 and SPINK6/9. There was no clear link with atopy or with FLG mutations. CONCLUSIONS: Our study suggests premature corneodesmolysis as the main pathological mechanism of this palmoplantar skin disorder. We conclude that KE appears to be a distinct peeling entity.

Ultrastructure of acantholysis in pemphigus foliaceus re-examined from the current perspective.

BACKGROUND: Pemphigus foliaceus (PF) is a chronic cutaneous autoimmune blistering disease that is characterized by superficial blistering of the skin, and according to the current perspective is caused by autoantibodies directed against desmoglein (Dsg) 1. OBJECTIVES: To examine early acantholysis in the skin of patients with PF at an ultrastructural level. METHODS: Two Nikolsky-negative (N-), five Nikolsky-positive (N+) and two lesional skin biopsies from immunoserologically defined patients with PF were studied by light and electron microscopy. RESULTS: We found no abnormalities in N- PF skin, whereas all the N+ skin biopsies displayed intercellular widening between desmosomes, a decreased number of desmosomes and hypoplastic desmosomes in the lower epidermal layers. Acantholysis was present in two of five N+ biopsies, but only in the upper epidermal layers. The lesional skin biopsies displayed acantholysis in the higher epidermal layers. Hypoplastic desmosomes were partially (pseudo-half-desmosomes) or completely torn off from the opposing cell. CONCLUSION: We propose the following mechanism for acantholysis in PF: initially PF IgG causes a depletion of nonjunctional Dsg1, leading to intercellular widening between desmosomes starting in the lower layers and spreading upwards. Depletion of nonjunctional Dsg1 impairs the assembly of desmosomes, resulting in hypoplastic desmosomes and a decreased number of desmosomes. In addition, antibodies might promote disassembly of desmosomes. In the upper layers of the epidermis, where Dsg3 is not expressed and cannot compensate for Dsg1 loss, ongoing depletion of Dsg1 will finally result in a total disappearance of desmosomes and subsequent acantholysis.

IgG-induced clustering of desmogleins 1 and 3 in skin of patients with pemphigus fits with the desmoglein nonassembly depletion hypothesis.

BACKGROUND: In pemphigus circulating IgG is present with the desmosomal cadherins desmoglein (Dsg) 1 and 3. In the epidermis of patients, this IgG deposits in a pattern that is often partly granular and does not reflect the normal Dsg distribution. OBJECTIVE: To understand why the IgG deposits in a granular pattern in the skin of patients with pemphigus. PATIENTS/METHODS: We analysed the distribution of IgG and desmosomal adhesion molecules in skin biopsies of 18 patients with pemphigus vulgaris (PV) and 10 with pemphigus foliaceus (PF) by double staining immunofluorescence. The effect of IgG on desmosomal proteins was studied in an in vitro skin model. RESULTS: In PF skin Dsg1, but not Dsg3, was aberrantly distributed in the same partly granular pattern as the IgG. Vice versa, in skin of PV patients with anti-Dsg3 antibodies, Dsg3, but not Dsg1, colocalized with the granular IgG. Plakoglobin also coclustered with IgG and Dsg, but this was far more prominent with Dsg1 than with Dsg3. In areas of heavy Dsg1 clustering, but not in areas of heavy Dsg3 clustering, intercellular widening between keratinocytes was present. Patient IgG, but not Fab fragments, induced the same Dsg clustering in vitro. CONCLUSIONS: The IgG-induced clustering of the Dsg autoantigens underlies the granular IgG deposition in patient skin. In PF and in mucocutaneous PV, Dsg1 clustering, but not Dsg3 clustering, correlates with nonacantholytic intercellular widening between desmosomes. In the patient the Dsg becomes sequestered from desmosomal components which fits in with the desmoglein nonassembly depletion hypothesis, indicating that targeted nonjunctional Dsg is no longer available to be incorporated into desmosomes and this leads to disturbed assembly, and Dsg-depleted desmosomes.