PemphigusEdit
Pemphigus refers to a group of rare autoimmune blistering disorders characterized by the loss of cell-to-cell adhesion in the epidermis and mucous membranes. The pathogenic mechanism involves autoantibodies directed at desmosomal cadherins, most notably desmoglein-1 and desmoglein-3, which hold keratinocytes together. This immune attack leads to intraepidermal blisters and erosions that can be painful and functionally disabling. The condition is unpredictable and requires specialized care, but advances in immunosuppressive therapy have substantially improved outcomes in many patients. For background, see Autoimmune blistering diseases and Desmoglein.
The clinical spectrum of pemphigus includes several main variants, with pemphigus vulgaris, pemphigus foliaceus, and paraneoplastic pemphigus being the most clinically significant. Pemphigus vulgaris (PV) usually presents with mucosal involvement early, often followed by skin lesions. Pemphigus foliaceus (PF) typically involves the skin and spares mucous membranes. Paraneoplastic pemphigus (PNP) is associated with an underlying neoplasm and tends to have a more aggressive course. Diagnosis relies on a combination of clinical observation, histopathology, and immunofluorescence, and treatment relies on immunosuppression and, in many cases, targeted biologic therapy. See Pemphigus vulgaris, Pemphigus foliaceus, and Paraneoplastic pemphigus for detailed variants.
Types of pemphigus
Pemphigus vulgaris
PV is the most common form and is characterized by painful mucosal erosions, often with subsequent skin involvement. Flaccid bullae rupture easily, leaving shallow wounds. The Nikolsky sign—gentle pressure causing the blister to extend—is frequently positive. The immunopathology typically shows autoantibodies against desmoglein-3, and sometimes desmoglein-1, leading to mucosal predilection and varying skin involvement. See Nikolsky sign and Desmoglein.
Pemphigus foliaceus
PF mainly affects the skin with crusted erosions and scales; mucosal involvement is uncommon. Autoantibodies are directed primarily against desmoglein-1, which explains the cutaneous-limited pattern. Histology reveals superficial (subcorneal) acantholysis, and direct immunofluorescence shows intercellular IgG in the upper epidermis. See Desmoglein-1 and Acantholysis.
Paraneoplastic pemphigus
PNP occurs in the setting of an underlying malignancy, most often lymphoproliferative disorders or thymic tumors. It features severe mucosal disease and polymorphic skin lesions and is associated with a poorer prognosis compared with non-paraneoplastic forms. The pathophysiology involves autoantibody cross-reactivity with multiple epithelial antigens and immune dysregulation linked to the neoplasm. See Paraneoplastic pemphigus and Autoimmune blistering diseases.
Pathophysiology
Pemphigus arises from autoantibodies that disrupt desmosomes, the intercellular junctions that maintain epidermal cohesion. Most patients develop IgG autoantibodies against desmoglein-1 and/or desmoglein-3; these antibodies interfere with keratinocyte adhesion and trigger acantholysis. The distribution of autoantibodies helps explain the clinical pattern: mucosal involvement is more common when anti–desmoglein-3 antibodies predominate, while desmoglein-1–focused responses favor cutaneous disease. Desmosomal biology and the concept of antibody-mediated disruption of cell–cell adhesion are central to understanding the disease, and research continues into targeted therapies and personalized approaches. See Desmoglein, Acantholysis.
Diagnosis
Diagnosing pemphigus requires a combination of clinical assessment, tissue biopsy, and immunologic testing. Histopathology on a lesional or perilesional biopsy typically shows intraepidermal acantholysis with a characteristic “row of tombstones” basal layer. Direct immunofluorescence on perilesional skin or mucosa reveals intercellular IgG (and often C3) deposition within the epidermis. Serologic testing can detect anti-desmoglein antibodies and help distinguish PV from PF. See Direct immunofluorescence and Acantholysis.
Treatment
Management aims to control disease activity, minimize blisters and erosions, prevent complications, and reduce long-term treatment-related harm. Initial therapy commonly involves systemic corticosteroids to rapidly suppress immune activity, followed by tapering. To lower the exposure to steroids and reduce relapse risk, many patients receive steroid-sparing agents such as azathioprine, mycophenolate mofetil, methotrexate, or cyclophosphamide. Rituximab, a monoclonal antibody against CD20 on B cells, has become a widely used option and can induce long-lasting remissions in a substantial portion of patients, sometimes allowing complete withdrawal of steroids. In difficult cases, plasmapheresis or immunoadsorption may be employed to remove pathogenic antibodies. Supportive care, wound management, infection prevention, and nutrition support are important components of comprehensive care. See Rituximab, Corticosteroids, Azathioprine, Mycophenolate mofetil.
Prognosis and management considerations
Prior to modern immunosuppressive therapy, pemphigus carried a high mortality rate. With current treatments and specialized care, prognosis has improved markedly, though the disease remains serious and requires ongoing monitoring for infection, medication toxicity, and disease activity. Outcomes vary with subtype, extent of mucosal and skin involvement, and response to therapy, as well as access to expertise and appropriate medications. See Autoimmune blistering diseases.
Epidemiology and risk factors
Pemphigus is rare, with incidence and prevalence varying by region and ethnicity. Endemic forms of pemphigus foliaceus have been described in certain areas, and genetic susceptibility (for example, particular HLA alleles) appears to influence risk in some populations. The distribution of disease across age groups and sexes is variable by subtype. See Endemic pemphigus and HLA.