Depigmentation therapy in vitiligo universalis with topical 4-methoxyphenol and the Q-switched ruby laser

Background: Monobenzylether of hydroquinone is used worldwide to remove residual pigment in patients with vitiligo universalis. Because of the side effects reported with this drug, the use of monobenzylether of hydroquinone has been restricted in The Netherlands. Objective: Our purpose was to evaluate the long-term effectiveness and safety of a combination therapy consisting of topical 4-methoxyphenol (4-MP) cream and Q-switched ruby (QSR) laser in 16 patients with vitiligo universalis. Methods: In a retrospective study patient record forms were evaluated. Data were collected regarding history as well as physical and histologic examination. The patients came to the institute for a follow-up visit after a treatment-free period of 2 to 36 months. Results: Thirteen patients received both therapies. Three patients only used the cream. None of the areas was treated by the cream and QSR laser at the same time. In 11 of the 16 patients (69%; 95% confidence interval [CI], 41%-89%) total depigmentation was achieved using the 4-MP cream. Onset of depigmentation was between 4 and 12 months. Four of the 5 patients who did not respond to the 4-MP cream had successful depigmentation with the QSR laser. Mild burning or itching was reported with the cream in 4 cases (25%). Of the 11 patients who responded to the 4-MP cream, 4 had recurrence of pigmentation (relapse rate of 36%; 95% CI 11%-69%) after a treatment-free period of 2 to 36 months. In 9 of the 13 patients (69%; 95% CI, 39%-91%) total depigmentation was achieved after QSR laser therapy. Onset of depigmentation was between 7 and 14 days after the treatment. Three of the 4 unresponsive patients showed total depigmentation after application of the 4-MP cream. No side effects were observed. Of the 9 patients who responded to QSR laser therapy, 4 had recurrence of pigmentation (relapse rate of 44%; 95% CI, 14%-79%) after a treatment-free period of 2 to 18 months. These patients had a negative Koebner phenomenon. Conclusion: Depigmentation therapy using a 4-MP cream and/or QSR laser therapy is an effective and safe method to remove disfiguring residual pigment in patients with vitiligo universalis. Patients should be warned that repigmentation may occur, even after total depigmentation has been achieved

IgA-mediated epidermolysis bullosa acquisita: Two cases and review of the literature

We describe 2 adult patients with a subepidermal bullous dermatosis with exclusively linear IgA depositions along the epidermal basement membrane zone that were deposited in the sublamina densa zone as witnessed by direct immunoelectron microscopy. Indirect immunofluorescence microscopy of patients' sera revealed circulating IgA autoantibodies that bound exclusively to the dermal site of salt-split skin substrate. Immunoblot analysis using dermal and keratinocyte extracts were negative. Indirect immunofluorescence microscopy using type VII collagen-deficient skin ("knockout" substrate) showed no IgA binding, whereas linear IgA binding was seen at the epidermal basement membrane zone in normal human skin. The autoantigen in the patients was thus type VII collagen. A diagnosis of IgA-mediated epidermolysis bullosa acquisita (IgA-EBA) was made. We systematically reviewed the literature of this subset of patients with linear IgA dermatosis on the basis of the following criteria: exclusive binding of serum-IgA to the dermal side of salt-split skin or IgA depositions in the sublamina densa zone by indirect or direct immunoelectron microscopy. We learned that IgA-EBA is clinically indistinguishable from the classic "lamina-lucida type" linear IgA dermatosis or from the inflammatory type of IgG-mediated epidermolysis bullosa acquisita (IgG-EBA). Only a minority of the patients with IgA-EBA showed milia or scarring or had therapy-resistant ocular symptoms as in the mechanobullous type of IgG-EBA. Most patients with IgA-EBA responded to dapsone therapy

U-serrated immunodeposition pattern differentiates type VII collagen targeting bullous diseases from other subepidermal bullous autoimmune diseases

Background Epidermolysis bullosa acquisita (EBA) can be differentiated from other subepidermal bullous diseases by sophisticated techniques such as immunoelectron microscopy, salt-split skin antigen mapping, fluorescence overlay antigen mapping, immunoblot and enzyme-linked immunosorbent assay. Objectives To determine whether the diagnosis can also be made by routine direct immunofluorescence microscopy. Methods We studied frozen skin biopsies from 157 patients with various subepidermal immunobullous diseases. Results We found three distinct 'linear' fluorescence patterns at the basement membrane zone: true linear, n-serrated and u-serrated. The true linear pattern, often seen in conjunction with either the n- or the u-serrated pattern, was found in any subepidermal immunobullous disease with non-granular depositions. In bullous pemphigoid, mucous membrane pemphigoid, antiepiligrin cicatricial pemphigoid, p200 pemphigoid and linear IgA disease the n-serrated pattern was found, corresponding with depositions located in hemidesmosomes, lamina lucida or lamina densa. However, in EBA and bullous systemic lupus erythematosus the u-serrated staining pattern was seen, corresponding with the ultralocalization of type VII collagen in the sublamina densa zone. The diagnosis of EBA with IgG or IgA autoantibodies directed against type VII collagen was confirmed by immunoelectron microscopy, salt-split skin antigen mapping, fluorescence overlay antigen mapping or immunoblotting. Conclusions Using this pattern recognition by direct immunofluorescence microscopy we discovered several cases of EBA which would otherwise have been erroneously diagnosed as a form of pemphigoid or linear IgA disease

Anti-epiligrin cicatricial pemphigoid and epidermolysis bullosa acquisita: Differentiation by use of indirect immunofluorescence microscopy

Binding of autoantibodies to laminin 5 and type VII collagen causes anti-epiligrin cicatricial pemphigoid and epidermolysis bullosa acquisita, respectively. Differentiation between these two dermal-binding autoimmune bullous dermatoses is not yet possible by indirect immunofluorescence microscopy. In this study we tested whether two recently described immunofluorescence techniques, "knockout" skin substrate and fluorescent overlay antigen mapping, can differentiate between anti-epiligrin cicatricial pemphigoid and epidermolysis bullosa acquisita. A total of 10 sera were tested: 4 with antilaminin 5, and 6 with antitype VII collagen autoantibodies, as characterized by either immunoblot or immunoprecipitation analysis. Differentiation between anti-epiligrin cicatricial pemphigoid and epidermolysis bullosa acquisita was possible in all 10 sera by indirect immunofluorescence using either knockout skin substrate or fluorescent overlay antigen mapping technique. (J Am Acad Dermatol 2003;48:542-7.)