Pemphigus Vulgaris: Symptoms, Types, Causes and Treatment

Pemphigus vulgaris is a rare but potentially life-threatening autoimmune disease that disrupts the connection between skin and mucous membrane cells, leading to painful blisters and erosions. Although this condition is uncommon, its impact on quality of life and the complexity of its management make awareness and understanding essential for patients, families, and healthcare professionals alike. This article offers a comprehensive, evidence-based overview of pemphigus vulgaris—covering its symptoms, types, causes, and treatment strategies—synthesized from the latest research.

Symptoms of Pemphigus Vulgaris

Pemphigus vulgaris (PV) often begins subtly but can rapidly progress to severe, widespread blistering. Recognizing its symptoms early is crucial for timely diagnosis and management, as untreated PV can be life-threatening. The symptoms can vary widely between individuals and may affect both the skin and mucous membranes.

Symptom Area	Key Features	Notes/Complications	Source(s)
Oral Mucosa	Painful erosions, ulcers	Usually first site, precedes skin	1 2 5
Skin	Flaccid blisters, erosions	Blisters rupture easily; Nikolsky sign positive	2 3 5
Other Mucosa	Nose, eyes, genitals	Can cause swallowing, breathing, or vision issues	1 2
General	Pain, dysphagia, fetor	May impair nutrition and quality of life	1 2 9

Table 1: Key Symptoms

Oral and Mucosal Symptoms

PV most commonly begins with painful erosions inside the mouth—affecting the cheeks, gums, tongue, or palate. These erosions often precede any skin involvement and are frequently misdiagnosed as other oral conditions, delaying proper treatment. In some patients, the disease remains confined to the mucosa, while in others, it progresses to involve the skin 1 2 5.

Skin Manifestations

Skin involvement typically appears as fragile, flaccid blisters that rupture easily, leaving raw, painful erosions. These lesions can occur anywhere but are often found on the scalp, chest, back, and intertriginous areas. The Nikolsky sign—a clinical test where gentle rubbing of the skin causes the outer layer to slough off—can be positive and is a diagnostic hallmark 2 3.

Other Mucosal Sites

Less commonly, PV can affect other mucous membranes, including the eyes, nose, throat, and genitals. This can lead to additional complications, such as difficulty swallowing, vision problems, or painful urination 1 2.

Systemic Effects and Complications

The pain and discomfort of PV can severely impact daily life, making eating, speaking, or even moving difficult. Persistent erosions may lead to secondary infections, fluid loss, and nutritional deficiencies. Without treatment, the disease can be fatal due to these complications 2 9.

Types of Pemphigus Vulgaris

Pemphigus vulgaris is not a single, uniform disease but encompasses several subtypes and clinical variants, each with distinct presentations and underlying mechanisms. Understanding these types is important for accurate diagnosis and personalized treatment.

Type	Main Features	Distinguishing Factors	Source(s)
Mucosal-Dominant	Oral or mucosal lesions only	Anti-Dsg3 autoantibodies	4 5 6 10
Mucocutaneous	Both skin and mucosa affected	Anti-Dsg3 & Dsg1 antibodies	4 5 6
Cutaneous Type	Skin only, rare	Predominant anti-Dsg1	4
Variants	Vegetans, Herpetiformis	Unique clinical/histo features	1 3

Table 2: Pemphigus Vulgaris Types

Mucosal-Dominant Pemphigus Vulgaris

This classic form involves erosive lesions limited to the mucous membranes, primarily the oral cavity. It is most strongly associated with autoantibodies against desmoglein 3 (Dsg3), a key adhesion molecule in mucosal epithelial cells. Patients may suffer for months with oral pain and ulcers before any skin involvement appears 4 5 6 10.

Mucocutaneous Pemphigus Vulgaris

In this subtype, both the skin and mucous membranes are affected. Autoantibodies target both Dsg3 and desmoglein 1 (Dsg1), leading to the characteristic combination of mucosal erosions and widespread skin blistering 4 5 6.

Cutaneous (Skin-Only) PV

A rare variant, cutaneous PV presents with blisters and erosions only on the skin, without any visible mucosal involvement. This form is thought to occur when anti-Dsg1 antibodies are dominant and anti-Dsg3 activity is weak or transient. It may evolve into, or from, other subtypes during the disease course 4.

Other Variants

• Pemphigus vegetans: Features vegetating, wart-like plaques in skin folds.
• Pemphigus herpetiformis: Presents with grouped, herpes-like blisters but shares PV immunopathology.
• Paraneoplastic pemphigus: Linked with underlying malignancies and has features of multiple pemphigus types 1 3.

Causes of Pemphigus Vulgaris

The root cause of pemphigus vulgaris is a malfunction of the immune system, but the pathways leading to disease are complex and influenced by genetic and environmental factors.

Factor	Role in PV	Explanation/Example	Source(s)
Autoantibodies	Direct cause	Target Dsg3, Dsg1, desmocollin 3	1 5 6 9 10
Genetics	Predisposition	HLA-DRB104:02, DQB105:03 alleles	1 9 12
Immune Cells	Disease mediation	T and B cell interaction, IgG4	9 11 12
Triggers	Disease onset/progression	Drugs, stress, infections possible	11

Table 3: PV Causes and Mechanisms

Autoantibodies and Loss of Cell Adhesion

Pemphigus vulgaris is defined by the presence of IgG autoantibodies that target desmosomal proteins—mainly desmoglein 3 (Dsg3), desmoglein 1 (Dsg1), and sometimes desmocollin 3. These proteins are essential for the adhesion between keratinocytes in skin and mucosa. When antibodies disrupt these bonds, cells lose contact (a process called acantholysis), resulting in the characteristic blisters and erosions 1 5 6 9 10.

Genetic Susceptibility

Genetics play a strong role in predisposing individuals to PV. Certain HLA class II alleles, particularly HLA-DRB104:02 and DQB105:03, are more common in affected patients. These genes are involved in immune system regulation and antigen presentation, increasing the likelihood of developing the autoantibody response seen in PV. Familial cases and higher prevalence in certain ethnic groups further support a genetic basis 1 9 12.

Immune System Dysfunction

Both T and B lymphocytes are involved in the pathogenesis. Research shows that autoreactive CD4+ T helper cells stimulate B cells to produce the pathogenic IgG—especially the IgG4 subclass—against desmoglein proteins. The breakdown in immune tolerance is multifactorial and not yet fully understood 9 11 12.

Environmental Triggers

While genetics set the stage, environmental factors may trigger disease onset or exacerbation. Certain medications (e.g., penicillamine, captopril), infections, trauma, and even psychological stress have been reported as possible triggers, though no single factor is necessary or sufficient for disease development 11.

Treatment of Pemphigus Vulgaris

Managing pemphigus vulgaris requires a balance between controlling the autoimmune response and minimizing treatment side effects. Advances in therapy have drastically improved outcomes, but individualized, multidisciplinary care remains essential.

Treatment	Purpose/Mechanism	Indications/Notes	Source(s)
Corticosteroids	Immunosuppression	First-line, rapid effect	1 5 7 14
Immunosuppressants	Steroid-sparing, control	Azathioprine, MMF, cyclophosphamide	1 7 14 15
Rituximab	B-cell depletion	Severe/refractory, now first-line	5 7 13 17
IVIG, Plasmapheresis	Remove autoantibodies	Severe, refractory cases	6 7 13
Topical Agents	Local symptom control	Mild/limited disease	7

Table 4: Treatment Approaches

Corticosteroids

Systemic corticosteroids (such as prednisone) are the mainstay of initial PV treatment. They act rapidly to suppress inflammation and halt new blister formation. High doses are often required, but long-term use carries risks such as diabetes, osteoporosis, and infection. Early and aggressive steroid therapy has dramatically reduced PV mortality 1 5 7 14.

Immunosuppressive Agents

To reduce steroid dependence and minimize side effects, additional immunosuppressive drugs are often used:

• Azathioprine and mycophenolate mofetil (MMF) are common choices and have shown efficacy in combination with prednisone 7 14 15 16.
• Cyclophosphamide may be used in severe or refractory cases. These agents act by suppressing the immune response that produces pathogenic antibodies 7 14 15.

Rituximab

Rituximab, a monoclonal antibody targeting CD20 on B cells, has revolutionized PV treatment. It effectively depletes B cells, reducing antibody production. Recent studies have shown rituximab to induce long-term remission in up to 90% of patients, often allowing for rapid steroid tapering and fewer side effects. It is now considered a first-line treatment for moderate to severe PV in many guidelines 5 7 13 17. Protocols vary, but both lymphoma and rheumatoid arthritis dosing regimens are effective.

Intravenous Immunoglobulin (IVIG) and Plasmapheresis

In patients with severe, refractory disease or those who cannot tolerate other immunosuppressants, IVIG and plasmapheresis may be used. These treatments help by removing pathogenic antibodies from the bloodstream or providing immune modulation 6 7 13.

Topical and Supportive Therapies

For localized disease, topical corticosteroids may be sufficient. Supportive care, including wound management, pain control, nutritional support, and infection prevention, is vital for all patients 7 16.

Multidisciplinary and Long-Term Care

PV is a chronic disease with potential relapses. Ongoing monitoring, patient education, and collaboration between dermatologists, dentists, and other specialists are essential for optimal outcomes 2 16.

Conclusion

Pemphigus vulgaris is a complex autoimmune disease that requires early recognition, accurate diagnosis, and carefully tailored treatment. Advances in immunology have transformed its prognosis, but lifelong management and vigilance remain important.

Key Points:

• Symptoms: Painful oral erosions are the earliest and most common symptom, followed by flaccid skin blisters and possible involvement of other mucous membranes 1 2 5.
• Types: PV presents in several forms—mucosal-dominant, mucocutaneous, and rarely cutaneous-only—each with distinct antibody profiles and clinical features 4 5 6.
• Causes: Disease is driven by autoantibodies against desmoglein proteins, with genetic and immune factors playing key roles. Environmental triggers may initiate or exacerbate disease 1 5 9 12.
• Treatment: Corticosteroids remain the cornerstone, but rituximab and other immunosuppressants have dramatically improved outcomes. Long-term, multidisciplinary management is crucial 5 7 13 16.

By staying informed and fostering multidisciplinary care, both patients and providers can work together to manage pemphigus vulgaris effectively and improve quality of life.