Pemphigus erythematosus associated with anti-DNA antibodies and multiple anti-ENA antibodies: a case report

Pemphigus erythematosus (PE) is an autoimmune blistering disease combining features of pemphigus foliaceus (PF) and systemic lupus erythematosus (SLE). We report a case of PE associated with anti-double-stranded DNA (anti-dsDNA), anti-Smith (anti-Sm), anti-Ro (anti-SSA), and antiribonucleoprotein (anti-RNP) antibodies. This case required extensive immunosuppressive therapy. We treated our patient with a combination of systemic steroids, intramuscular gold injections, azathioprine, and hydroxychloroquine. The patient's response was complete remission--evaluated clinically, serologically, and immunohistochemically.     

Clinical significance and correlation of antinuclear antibodies and anti-DNA antibodies.

The clinical significance and correlation of antinuclear antibodies (ANA) and anti-DNA antibodies was studied using 142 ANA positive sera from different patients having various diseases. High titers of ANA were found briefly in systemic lupus erythematosus and sometimes in scleroderma or mixed connective tissue disease. The peripheral pattern of ANA was seen exclusively in systemic lupus erythematosus and occasionally in mixed connective tissue disease. Anti-DNA antibodies could be found in systemic lupus erythematosus, discoid lupus erythematosus, scleroderma, chronic active hepatitis, but a high titer of anti-DNA (over 60 unit/ml) was present only in patients with systemic lupus erythematosus, especially those having lupus nephritis. There was little correlation between ANA and anti-DNA antibodies.     

Pemphigus antibodies fixation and keratinocyte differentiation in organ cultures

Summary The effect of some agents, influencing the cyclic adenosine 3,5-monophosphate (cAMP) content of human cells, on the ability of the keratinocytes of binding pemphigus antibodies was studied by using tissue cultures of rabbit esophagus. As demonstrated by immunofluorescence (IF) for IgG, the bound antibodies appeared markedly decreased on esophagus explants grown under standard conditions, that is without test agents, when compared to ones fixed on fresh esophagus. But the IF reaction was remarkably more intense when methylxanthines or epinephrine were added to the growth medium of the cultures. Following the addition of these agents to the cultures some histologic modifications appeared in the explants, indicating that the keratinization process had probably been stimulated. This temporal relationship of immunofluorescence and histologic findings seems to suggest the hypothesis that keratinocyte differentiation, regulation of cAMP intracellular content, and pemphigus antibodies fixation are related processes.     

Pemphigus herpetiformis with IgA and IgG antibodies to desmoglein 1 and IgG antibodies to desmocollin 3

We describe a case with clinical and histologic features of pemphigus herpetiformis associated with IgG and IgA anti-keratinocyte cell surface antibodies to desmoglein 1 (Dsg1) and exclusively IgG antibodies to desmocollin 3 (Dsc3). The clinical presentation was somewhat similar to IgA pemphigus; the main difference was the prevailing association with IgG antibodies to Dsg1. The presence of IgA anti-Dsg1 antibodies was confirmed by IgA enzyme-linked immunosorbent assay and IgG anti-Dsc3 antibodies were detected by a novel enzyme-linked immunosorbent assay with the use of baculovirus expressing recombinant Dscs for IgG and IgA. The reactivity of IgG antibodies with Dsc3 was confirmed by COS-7 cell cDNA transfection method using cDNA of human Dsc1 to Dsc3. We discuss the differentiation of pemphigus herpetiformis, associated with both IgG and IgA antibodies, from IgA pemphigus, particularly in regard to the autoimmune reaction with Dsgs and Dscs.     

Pemphigus

Pemphigus is an autoimmune intraepithelial blistering disease of the skin and mucous membranes that is characterized in part by the presence of circulating IgG autoantibodies. These autoantibodies, which have been shown to be pathogenic, bind to complexes on the keratinocyte cell surface and have been utilized to establish that these complexes contain components found in cell adhesion junctions. Although the stimulus for autoantibody production is unknown, proposed mechanisms to explain the disease pathophysiology include proteinase activation, complement activation, and direct interference of cell adhesion junction assembly by autoantibodies. Although pemphigus vulgaris was commonly fatal prior to the availability of glucocorticosteroids, the prognosis has improved dramatically since their introduction. Immunosuppressive agents have also been successfully employed to treat patients with more severe disease.     

Pemphigus

Pemphigus refers to a group of potentially life‐threatening autoimmune diseases of the skin and mucous membranes, characterized by the formation of blisters and erosions of the skin. An autoimmune process, directed against keratinocyte desmosomal cadherins, interferes with the adhesive function of these molecules. This results in the separation of keratinocytes and clinical manifestation of blistering. Differences in the particular antigens targeted by the antibodies and in the distribution of these antigens in the different regions of the body and in the separate layers of the epidermis result in different clinical manifestations of the disease. Diagnosis of pemphigus is based on three independent groups of criteria: clinical features (flaccid blisters and erosions on skin and oral mucosa), histologic findings (epidermal acantholysis) and immunological tests (circulating and skin‐fixed antibodies against keratinocyte surface antigens). The principle aim of treatment is to reduce inflammatory response and autoantibody production, thereby achieving disease remission. Systemic corticosteroids are still the most useful drugs in the treatment of pemphigus and continue to be the mainstay of therapy for this disease. Adjuvant drugs, such as immunosuppressants, are commonly used in combination, in order to increase efficacy and have a steroid‐sparing effect, thereby allowing reduced maintenance doses and less side effects of systemic corticosteroids. Other options include intravenous immunoglobulin and plasmapheresis. However, more research is needed to develop treatments with the least possible toxicity.     

Pemphigus

Pemphigus is a group of organ-specific autoimmune mucocutaneous disorders with an established immunologic basis. The presence of intraepithelial blisters and erosions of the skin and variable involvement of the mucous membranes characterize its three major variants, pemphigus vulgaris, pemphigus foliaceus, and paraneoplastic pemphigus. Prior to the use of corticosteroids in the 1950s, the natural history of pemphigus vulgaris was relentless progression, with a 50% mortality at 2 years, and almost 100% at 5 years. Today, with mortality rates less than 5%, the focus has changed towards reducing corticosteroid side effects and maintaining optimal quality of life under treatment. This can be achieved by the appropriate use of steroid-sparing agents. This article addresses the comprehensive management of patients with pemphigus.     

Pemphigus

The term pemphigus refers to a group of autoimmune intraepidermal blistering diseases of the skin and mucous membranes. Several clinical variants of pemphigus are recognized. The major histologic feature of all variants is acantholysis, the disruption of normal cell-to-cell adhesion, which leads to intraepidermal blister formation. Most patients with pemphigus demonstrate IgG autoantibodies directed against an antigen located on the surface of keratinocytes. Although the stimulus for autoantibody production is unknown, several mechanisms have been proposed to explain the pathogenesis of acantholysis. One popular model proposes that pemphigus antibodies induce acantholysis through local stimulation of the plasminogen-plasmin system. Another model proposes that pemphigus antibodies fix complement and thereby alter cell membrane integrity to produce acantholysis. Prior to the availability of corticosteroids, pemphigus vulgaris was commonly fatal. Treatment with glucocorticosteroids has drastically improved the prognosis. Immunosuppressive agents and plasmapheresis have been used successfully in some patients with severe disease.     

Pemphigus

Pemphigus is an infrequent, organ-specific, autoimmune bullous disease, which affects the skin, mucous membranes and appendages. Histopathologically, it is characterized by acantholysis. Pemphigus has classically been divided into two major groups, pemphigus vulgaris and pemphigus foliaceus, with their respective clinical variants pemphigus vegetans and pemphigus erythematosus. In recent years, new variants of pemphigus have been described: paraneoplastic pemphigus, IgA pemphigus and pemphigus herpetiformis. This article reviews the epidemiology, etiopathogenesis, clinical symptoms, diagnosis, treatment and prognosis of pemphigus. Advances in molecular biology techniques have made it possible to more precisely identify the different antigens against which antibodies are directed, and to fine-tune ELISA diagnostic techniques. Treating pemphigus vulgaris and foliaceus with general steroids has modified their prognosis; it is estimated that mortality in recent decades is less than 10 %. Managing the clinical complications that appear during the evolution of the pemphigus has contributed to reducing morbidity and mortality.     

Pemphigus

Pemphigus is an uncommon but potentially life-threatening chronic autoimmune bullous disorder. Antibodies are directed against antigens (desmoglein 1 and 3) in the desmosomes linking keratinocytes and against acetylcholine receptors. Conventional treatment with high-dose corticosteroids, sometimes with adjuvant immunosuppressive agents, may be associated with very serious adverse effects. There is an urgent need to establish the evidence for the safest and most effective form of treatment. A literature review has revealed 11 controlled (9 randomized) trials of treatment for pemphigus. The numbers of participants in the individual trials are small and the data cannot be pooled as they evaluate different forms of treatment. The results of these trials suggest that very high doses of corticosteroids, either as pulse therapy or in daily dosage, are not superior to moderate daily doses. Based on evidence from the available trials, addition of an immunosuppressive agent generally does not appear to offer substantial benefit in terms of clinical response. However, a recent study demonstrated a significant reduction in corticosteroid requirements among patients receiving immunosuppressive agents. Newer therapies, such as biologic agents (in particular rituximab), calcineurin inhibitors, or immunoadsorption appear promising but there are inadequate controlled trials to establish their role clearly. Initial open-label studies suggest that specific peptide immunotherapy may offer a safe and novel approach to the treatment of pemphigus in the future. At present, treatment of an individual patient with pemphigus requires clinical judgment and should not be based purely on guidelines or on the inadequate available evidence alone. There is an urgent need for large randomized, controlled, multicenter trials of treatment in patients with pemphigus.     

Pemphigus

Pemphigus diseases comprise a group of autoimmune disorders which are characterized by intraepidermal blisters and autoantibodies to components of desmosomes. Desmosomes mediate adhesion between neighbouring keratinocytes. A common feature of pemphigus diseases are intercellular deposits of IgG or, less frequently, of IgA within the epidermis. The group of pemphigus diseases includes pemphigus vulgaris, pemphigus foliaceus, pemphigus vegetans, pemphigus herpetiformis, pemphigus erythematosus, paraneoplastic pemphigus, drug-induced pemphigus, and IgA pemphigus. Using molecular tools, some of the autoantigens in these diseases have been characterized. In pemphigus vulgaris, autoantibodies are directed to desmoglein 3 and in pemphigus foliaceus to desmoglein 1. Target antigens in IgA pemphigus are desmocollin 1 and desmoglein 3. In paraneoplastic pemphigus, autoantibodies react with a complex of various proteins, including desmoplakin 1 and 2, BP230, envoplakin, periplakin, plectin, desmoglein 3, and a yet uncharacterized 170 kD protein. This review summarizes new insights into the immunopathogenesis and diagnosis of pemphigus diseases.