Mechanisms of Peripheral Tolerance

One mechanism of peripheral tolerance may be deletion, too. Deletion is mainly associated with the sudden appearance of a large number of antigens. This mechanism has been demonstrated for antigens that were presented in large numbers, thus during infection or following injection of superantigens Fig. 1. Modes of intrathymic selection of T cells. T cells with a very high affinity T cell receptor (TCR) for self major histocompatibility complexes (MHC) die from active deletion, those with an...

Clinical Manifestations

There is great diversity in the clinical presentation of EBA. The common denominator for patients with EBA is autoimmunity to type VII (anchoring fibrils) collagen and diminished anchoring fibrils (Woodley 1988 Woodley et al. 1988). Although the clinical spectrum of EBA is still being defined, it appears that there are at least five clinical presentations of EBA (Fig. 2) Fig. 2. Clinical presentations of Epidermolysis Bullosa Acquisita. A. Classical presentation in a white woman. B....

The Relationship between EBA and Bullous SLE

There have been reports of patients having both EBA and bullous SLE (Gammon and Briggaman 1993). In contrast to the classical presentation of EBA, bullous SLE patients by definition must fulfill the American Rheumatism Association criteria for SLE. The patients tend to be young women with a widespread nonscarring vesiculobullous eruption with a predilection for sun-exposed areas. EBA often presents in the fourth to fifth decades whereas bullous SLE usually presents earlier, in the second and...

Introduction

Localized scleroderma (LS) or morphea encompasses a group of disorders characterized by delimited and localized inflammatory sclerosis (thickening) and fibrosis of the skin, subcutaneous tissue, fascia and or adjacent muscle. In contrast to systemic sclerosis, Raynaud's phenomenon, acrosclerosis and internal organ involvement do not usually occur. Morphea may be divided into 5 subtypes plaque, generalized, bullous, linear and deep, based on the extent, form and depth of cutaneous sclerosis...

Summary

Pemphigus encompasses a group of life-threatening autoimmune blistering disorders characterized by intraepithelial blister formation. The molecular basis for intraepithelial blister formation is the loss of adhesion between kerati-nocytes, called acantholysis, which is caused by auto-Ab against intercellular adhesion structures of epidermal keratinocytes. Clinically, PV is characterized by extensive bullae and erosions of the mucous membranes and also of the skin (in case that anti-Dsgl auto-Ab...

Clinical Appearence Classification

The incidence of SSc is reported to be 2-20 million population and the prevalence 4-290 million population. Based on distinct clinical aspects and courses of the disease an internationally accepted classification was established with two forms limited cutaneous SSc (lSSc) and diffuse cutaneous SSc (dSSc). The disease is much commoner in females than males for reasons that are not entirely clear with a female-to-male ratio of 3-9 1. There are some populations at high risk as e.g. the Choctaw...

Morphea and Systemic Sclerosis SSc Incidence and Prevalence

Incidence and prevalence rates of SSc have been investigated in different large population based studies all over the world. Incidence data is rare which might be due to the fact that the definite time of onset of this disease is more difficult to determine. Incidence rates are lower than for SLE with a range of 3.7 to 19 106 inhabitants per year (Kaipiainen-Seppanen and Aho 1996 Mayes et al. 1996) and even more rare in children (Pelkonen et al. 1994 Fujikawa and Okuni 1997). Prevalence rates...

Cutaneous Manifestations

Before Gilliam and Sontheimer classified it as a distinct entity, lesions of SCLE were referred to with varied nomenclature including symmetric erythema centrifugum, disseminated DLE, autoimmune annular erythema, subacute disseminated LE, superficial disseminated LE, psoriasiform LE, pityriasiform LE, and maculopapular photosensitive LE (Sontheimer et al. 1979). Cutaneous lesions of SCLE typically begin with red macules or papules which evolve into psoriasiform and or annular plaques on...

Central Tolerance and Peripheral Tolerance

The thymus and the apoptosis and paralysis occurring during the development of B cells recognizing abundant antigens in the periphery delete about 90 of self-reactive T and B cells. This phenomenon is termed as central tolerance. However, roughly 10 of these cells survive (Blackman et al. 1990 Kisielow et al. 1988). Moreover, not all antigens are presented in thymus, bone marrow or peripheral blood. In one individual, all cells express the same MHC class I and a large spectrum of common minor...

Therapy

Treatment of DH should consider changes in both the skin and the intestine. Dapsone usually controls the skin eruption within days and this rapid response helped to support the clinical diagnosis of DH in the past. Dapsone is most commonly used in the treatment of skin lesions of DH. Although there are no Fig. 5. A. Histological examination of a skin biopsy from a newly developed lesion showing a subepidermal blister and a sparse superficial inflammatory infiltrate (low magnification). B. Next...

Therapy of Pemphigus

As mentioned above, the pemphigus disorders have severe morbidity and high mortality if untreated. Major complications of extensive blistering of skin and mucous membranes result from loss of body proteins and fluids, secondary bacterial infections and decreased food uptake due to painful oral erosions. The introduction of systemic glucorticosteroids has dramatically improved the prognosis of pemphigus. The strategy in PV is to induce complete remissions -no matter whether only oral lesions or...

Definition and Classification

Lupus erythematosus (LE) is a polyclonal T and B lymphocyte autoimmune disease thought to result from a complex interplay of genetic and environmental factors. Clinical expression of LE ranges in continuum from minor cutaneous lesions to life-threatening vital organ dysfunction. Throughout this continuum skin manifestations are variable and common. In 1981 Gilliam and Sontheimer developed a classification system that divides lesions into LE specific and LE non-specific cutaneous disease. LE...

Diagnosis

By definition, patients with EBA have IgG deposits within the DEJ of their skin (Yaoita et al. 1981). This is best detected by DIF of a biopsy specimen obtained from a perilesional site. The deposits are predominantly IgG, but, complement, IgA, IgM, Factor B and properidin may be detected as well (Kushniruk 1973 Yaoita et al. 1981). The DIF staining demonstates an intense, linear fluorescent band at the DEJ. Yaoita et al (1981) have suggested that a positive DIF and IgG deposits within the...

Clinical Features

In the prodromal, non-bullous phase manifestations of BP are frequently nonspecific and, thus, misleading. Patients complain of severe itch accompanied or not by excoriated, eczematiform, papular and or urticarial lesions that may persist for several weeks or months, or even remain the only signs of the disease. Fig. 1. Bullous pemphigoid. Panel A bullous lesions on the forearms Panel B urticarial erythema and elevated inflammatory plaques on the trunk distributed in a figurate pattern Panel C...

Autoantibody Reactivity against Desmogleins

PV is caused by auto-Ab against the extracellular portion (ECD) of desmog-lein 3 (Dsg3), a desmosomal adhesion molecule present on epidermal kerati-nocytes. Accordingly, PF is caused by auto-Ab against desmoglein 1 (Dsg1), a distinct desmosomal adhesion protein homologous but not identical with Fig. 1. Current concepts of the immune pathogenesis of pemphigus. Auto-Ab against Dsg1 and Dsg3 have been shown to induce loss of keratinocyte adhesion in pemphigus foliaceus (PF) and in pemphigus...

Etiology and Pathogenesis

The etiology of EBA is unknown, but because the disease features IgG autoantibodies directed against type VII collagen, it is thought that EBA has an autoimmune pathogenesis (Woodley et al. 1984,1988). Another autoimmune bullous skin disease which may exhibit auto-antibodies against type VII collagen is bullous systemic lupus erythematosus (SLE) (Gammon et al. 1985). Both EBA and bullous SLE patients often have a common human leukocyte antigen (HLA) major histocompatibility (MHC) class II cell...

Info

Epidermolytic Ichthyosis

Antinuclear antibodies (ANA) (Bunn et al. 1998), thus making the diagnosis of SSc in a patient without ANA quite unlikely. Although there is no antibody which can be related to disease activity like the presence of anti-ds DNA antibodies in systemic lupus erythematosus, patient classification according to serologic subsets can be meaningful. Nearly 85 of patients can be associated to one of seven SSc related antibodies (Table 1) and each of these antibodies describes a subset which to a...

Immunopathology

Direct immunofluorescence (DIF) is an adjunctive diagnostic test for all subsets of LE. DIF of lesional skin shows immunoglobulins (IgG, IgA, IgM) and complement components in a granular band-like pattern at the epidermal basement membrane (DEJ). In the original cohort (Sontheimer et al. 1979), 40 percent of SCLE patients had a negative DIF. Therefore a positive DIF can help to confirm the diagnosis of LE, but a negative test cannot rule it out. Nieboer et al. (1988) observed a...

Type 2 T Cells and TB Cell Interactions

A large number of autoimmune diseases is immunoglobulin mediated. These 'humoral' diseases can roughly be divided into two major categories. Immu-noglobulins can induce damage through direct binding of their target-antigen. This is the situation in most other bullous autoimmune diseases of the skin, especially pemphigus vulgaris. Alternatively immunoglobulins bind to circulating antigens and cause damage through deposition along basement membranes or in vessels. The former situation is given in...

Environmental Factors

Photosensitivity is seen in the majority of SCLE patients. UV light can induce the release of inflammatory mediators such as IL-1, TNF-a, IL-10 and oxygen free radicals at the level of the epidermis and dermis. In addition to natural light, cutaneous LE lesions have been provoked by exposure to psoralen with UVA Dowdy et al. 1989 McGrath et al. 1990 , UVB via unshielded fluorescent light Rihner and McGrath 1992 Kuhn et al. 2001 , radiation therapy Balabanova et al. 1997 , and...

Clinical Variants of Pemphigus

Pemphigus Folicaceous Epidermis

PV is a relatively rare disorder that primarily affects individuals in the 3rd to 5th decade without sex preference Huilgol et al. 1995 Nousari and Anhalt 1999 . PV is characterized by flaccid blisters erosions of the mucous membranes and the skin. In the majority of patients, the oral mucosa is primarily affected but other mucous membranes may be involved as well. Initial blisters rapidly rupture leading to painful chronic lesions that may affect larynx and pharynx in addition to the oral...

Clinical Appearance Classification

Pictures Ulcers From Lupus

Several distinctly different clinical entities can be allocated to the group of CCLE Table 2 . They may be found as one and only manifestation or associated with other forms of CCLE, localized or disseminated, both with and without systemic manifestations and varying relation to SLE. The most common Acute cutaneous lupus erythematosus ACLE Localized Subacute cutaneous lupus erythematosus SCLE Annular Papulosquamous Chronic cutaneous lupus erythematosus CCLE Discoid DLE Localized above neck...

Evidence Based Medicine and Epidemiology

Systematic Reviews on Autoimmune Diseases by the Cochrane Skin Group www. cochrane.org 2004 Table 2. Systematic Reviews on Autoimmune Diseases by the Cochrane Skin Group www. cochrane.org 2004 Drug treatments for discoid lupus erythematosus Cochrane Review Khumalo N, Kirtschig G, Middleton P, Hollis S, Woinarowska F, Murrell DF Interventions for bullous pemphigoid Cochrane Review Kirtschig G, Murrell D, Wojnarowska F, Khumalo N Interventions for mucous membrane pemphigoid and...