Pemphigus vulgaris is a rare and potentially life-threatening autoimmune  disease that affects the skin and mucous membranes. It is characterised by the formation of painful blisters and erosions due to autoantibodies targeting desmoglein proteins that are responsible for holding the skin cells together. Early and accurate diagnosis, followed by prompt and appropriate treatment, is crucial for managing this condition and improving the quality of life for patients.¹

Diagnosis of pemphigus vulagaris 

The diagnosis of pemphigus vulgaris involves a combination of clinical examination, histopathological evaluation, and immunological tests. Each of these components play a crucial role in establishing the correct diagnosis and ruling out other potential conditions.¹

Clinical examination

The clinical examination begins with a thorough onset and progression of symptoms, any potential triggers or underlying conditions, and any family history of autoimmune disorders. The physical examination focuses on the distribution, appearance, and severity of skin lesions, as well as the evaluation of mucosal involvement. 

In pemphigus vulgaris, the characteristic skin lesions are flaccid blisters that can easily rupture, leaving behind painful erosions or raw areas. These lesions can occur anywhere on the body, but they commonly appear on the scalp, face, trunk, and intertriginous areas (armpits, groin, and under the breasts). Mucosal involvement, particularly in the oral cavity, is also common, with the formation of blisters, erosions, and ulcerations on the lips, buccal mucosa, tongue, and palate.²

Histopathological examination

A skin biopsy is essential for the histopathological examination of pemphigus vulgaris. The biopsy sample should include an intact blister or the advancing edge of an erosion, as this area will provide the most diagnostic information. 

Under microscopic examination, the characteristic histological features of pemphigus vulgaris include: 

• Intraepidermal blister formation: The separation or cleavage occurs within the epidermis, typically the suprabasal layer (between the basal and spinous layer) 
• Acantholysis: This refers to the separation or ‘tearing apart’ of epidermal cells, leading to the formation of rounded, detached cells (known as Tzanck cells or acantholytic cells) 
• Inflammatory cell infiltration: The presence of inflammatory cells, such as eosinophils and neutrophils, within the blister cavity or surrounding the lesion.³

Immunological testing

Immunological tests are crucial for confirming the diagnosis of pemphigus vulgaris and distinguishing it from other autoimmune blistering diseases. These tests detect the presence of autoantibodies against desmoglein proteins, which are the primary targets in pemphigus vulgaris. 

• Direct Immunofluorescence (DIF): This test involves examining a skin biopsy sample under a fluorescence microscope after treating it with fluorescent labelled antibodies. In pemphigus vulgaris, the DIF typically shows intercellular deposition of immunoglobulins (IgG) and complement components along with epidermal cell surfaces, known as the ‘chicken wire’ or ‘honeycomb’ pattern.
• Indirect Immunofluorescence (IIF): This test detects circulating autoantibodies in the patient’s serum by incubating the serum with a substrate (usually monkey oesophagus or human skin) and then examining it under a fluorescence microscope. In pemphigus vulgaris, the IIF will show a characteristic intracellular staining pattern.
• Enzyme-linked immunosorbent assay (ELISA): This more advanced technique can quantify the levels of specific autoantibodies against desmoglein 1 (Dsg1) and desmoglein 3 (Dsg3), the two main target antigens in pemphigus vulgaris. 

While no single test is definitive, a combination of clinical, histopathological, and immunological findings is essential for establishing an accurate diagnosis of pemphigus vulgaris.^4,5 

Treatment of pemphigus vulgaris 

The treatment of pemphigus vulgaris aims to suppress the autoimmune response, control blistering, and promote healing. It typically involves a combination of systemic medications and supportive care measures. The specific treatment approach is tailored to each individual patient based on factors such as disease severity, response to therapy, and potential side effects. 

Corticosteroids 

Systemic corticosteroids, such as prednisolone or prednisone, are the first-line therapy for pemphigus vulgaris. These medications help suppress the autoimmune response and reduce blistering by inhibiting the production of inflammatory mediators and modulating the immune system. 

The initial dosage of corticosteroids is typically high (e.g.1-2 mg/kg/ day of prednisolone) to rapidly control disease activity. Once remission is achieved, the dosage is gradually tapered to the lowest effective maintenance dose to minimise side effects. However, long-term use of high-dose corticosteroids can lead to various adverse effects, including weight gain, osteoporosis, diabetes, and increased susceptibility to infections. 

Steroid-sparing immunosuppressants

To reduce the required dosage of corticosteroids and mitigate their side effects, steroid-sparing immunosuppressants are often used in combination with corticosteroids. These medications help suppress the immune system and maintain disease control while allowing for a lower corticosteroid dose. 

Common steroid-sparing immunosuppressants used in the treatment of pemphigus vulgaris include: 

• Azathioprine: This antimetabolite drug interferes with the proliferation and function of immune cells, particularly T cells and B cells. 
• Mycophenolate Mofetil: This medication selectively inhibits the proliferation of T cells and B cells by blocking the synthesis of guanine nucleotides. 
• Cyclophosphamide: A cytotoxic agent that suppresses the immune system by interfering with DNA synthesis and inhibiting cell division. 
• Methotrexate: An antimetabolite drug that inhibits the proliferation of rapidly dividing cells, including immune cells. 

These immunosuppressants carry their own risks of side effects, such as an increased susceptibility to infections, bone marrow suppression, and potential organ toxicity. Regular monitoring and dose adjustments are necessary to manage these side effects.⁶

Intravenous Immunoglobulin (IVIG)

Intravenous immunoglobulin (IVIG) therapy can be used as an adjunctive treatment or as a temporary measure in severe cases of pemphigus vulgaris or when other treatments are not effective. IVIG is a blood product derived from pooled human plasma that contains a diverse range of immunoglobulins. 

The mechanism of action of IVIG in pemphigus vulgaris are not fully understood, but they are believed to include: 

• Neutralising pathogenic autoantibodies through anti-idiotypic antibodies or by binding to the autoantibodies’ Fc regions. 
• Modulating the immune response by regulating various immune cell functions and cytokine production. 
• Providing immunomodulatory effects through the Fc portion of the immunoglobulins. 

IVIG therapy is generally well-tolerated, but potential side effects include headache, nausea, fever, and allergic reactions. It can also be associated with risks of thrombosis and aseptic meningitis.⁶

Rituximab 

Rituximab is a monoclonal antibody therapy that has shown promising results in the treatment of pemphigus vulgaris. It targets and deplete B cells, which are responsible for producing the autoantibodies against desmoglein proteins. 

Rituximab is typically administered intravenously in a series of infusions, either as a monotherapy or in combination with other immunosuppressants. It is considered  effective in inducing and maintaining remission in patients with pemphigus vulgaris, particularly in cases refractory to conventional therapies. 

While rituximab is generally well-tolerated, potential side effects include infusion reaction, increased risk of infections (due to B-cell depletion), and rare cases of progressive multifocal leukoencephalopathy (PML), a rare but potentially life-threatening brain infection.⁷

Supportive care 

In addition to systemic medications, supportive care measures are essential components of the treatment plan for pemphigus vulgaris. These measures include: 

• Wound care: Proper cleaning and dressing of blisters, erosions, and ulcers to prevent infection and promote healing. 
• Pain management: Analgesics and topical anaesthetics may be necessary to alleviate the pain associated with lesions, particularly in the oral cavity. 
• Fluid and electrolyte replacement: Severe cases of pemphigus vulgaris can lead to significant fluid and electrolyte imbalances due to extensive blistering and erosions, necessitating appropriate replacement therapy.
• Nutritional support: Oral lesions can make it difficult for patients to eat and maintain adequate nutrition, requiring dietary modifications or supplementation. 
• Psychological support: Pemphigus vulgaris can have a significant impact on a patient's quality of life and mental well-being, making psychological support and counselling essential components of the treatment plan.^8,9

Long-term management and monitoring

Pemphigus Vulgaris is a chronic condition that requires long-term management. Treatment is typically adjusted based on the patient’s response, disease activity, and potential side effects. 

Regular follow-up visits with a dermatologist or immunologist are essential to assess disease activity, monitor treatment efficacy, and adjust dosage or combination of medications as needed. Laboratory tests, such as complete blood counts, liver and kidney function tests, and immunological tests (e.g. ELISA for desmoglein antibodies), may be performed periodically to monitor disease activity and potential side effects. 

The goal of long-term management is to achieve and maintain remission while minimising the side effects of medications. In some cases, treatment may need to be adjusted or alternative therapies explored if remission is not achieved or if side effects become unmanageable.⁹  

Summary

Pemphigus vulgaris is a rare and potentially life-threatening autoimmune blistering disease that requires a comprehensive diagnostic approach involving clinical examination, histopathology, and immunoglobulin levels/activity?, and targeted therapies like rituximab. Long-term management, close monitoring, and supportive care are crucial for achieving and maintaining remission. 

Early diagnosis and appropriate treatment are essential to prevent complications, improve quality of life, and minimise the risk of potentially life-threatening complications. Ongoing research and advancements in therapies continue to improve the management and prognosis for patients with pemphigus vulgaris. 

FAQs

Is pemphigus vulgaris a contagious disease ?

No, pemphigus vulgaris is not contagious. It is an autoimmune disorder caused by the body’s immune system attacking its own skin cells, and it cannot be transmitted from person to person. 

Can pemphigus vulgaris go into remission ?

Yes, pemphigus vulgaris can go into remission with appropriate treatment. However, the disease is chronic, and remissions may be temporary or relapsing. Ongoing monitoring and treatment adjustments are often necessary to maintain long-term remission. 

Can pemphigus vulgaris be cured? 

Pemphigus vulgaris is a chronic autoimmune condition, and while it can be effectively managed with treatment, there is currently no definitive cure. The goal of treatment is to induce and maintain remission, control disease activity, and minimise complications.