What is Pemphigus Vulgaris?

Overview

Pemphigus vulgaris (PV) is a long-lasting and critical skin disease. The immune system attacks healthy cells in different body parts, like the mouth, lips, scalp, etc. It is common and mainly affects people aged 40 to 60. Primarily, blisters and skin break-outs are seen in the mouth that can spread to other areas. “Pemphigus” is taken from the Greek word Pemphix, which means blisters. In 1788, Stephen Dickson first observed pemphigus in a patient with a tongue blister.²

Causes

Pemphigus vulgaris is the most common variant. It is found all over the map and equally affects both genders. PV is sporadic, yet it affects mainly people ranging from 40 to 60 years of age. The specific reason for this has yet to be confirmed.² 

Autoimmune disorders

PV is a disorder where the body attacks its healthy skin by attacking desmogleins. Desmogleins are proteins that bind neighbouring skin cells. Invasion occurs to the desmogleins, leading to the eventual development of fluid-filled blisters. The areas affected include the skin, mouth, throat, moist tissues inside the nose, eyelids, and genital or other areas.

Medications

Some drugs used in treating rheumatoid arthritis and Wilson's disease can cause pemphigus.² 

Ancestral causes

People with Jewish or Mediterranean backgrounds, especially Ashkenazi Jewish descent, are more likely to develop pemphigus.

Genetic and environmental factors

Several environmental factors give rise to pemphigus in people with a genetic predisposition, for example, medications or any infection.

Tumours

It is an uncommon cause, but in some cases, tumours might produce PV.

Signs and symptoms 

• Most patients have mouth sores, often with or without skin sores
• PV is a long-lasting condition with moments of relief followed by worsening. If not treated timely, PV can turn into a deadly situation. A lot of skin is lost, leading to insufficient nutrients and fluids. Also, the person becomes prone to secondary infections (which may lead to septic shock)
• A typical feature of PV is Nikolsky's sign, in which the epidermis separates from the skin. It happens when applying pressure on the tip of the blister or normal skin
• Another feature is Asboe-Hansen or Nikolsky's II sign, in which the intact blister stretches on applying vertical pressure

Mouth sores

Mouth lesions are more common than skin lesions. These present with painful break-outs accompanied by easily bursting blisters. These blisters may be of many dimensions and forms. The main sites involved are buccal and palatine mucosa, lips, and gingiva.

The growth of a fissured hemorrhagic crust may damage the vermillion border of lips. The patient may deal with dysphagia and problems with eating. The disorder may continue for months, followed by skin lesions and other mucous membranes.

Other mucosal lesions

The conjunctiva, private areas, nasal mucosa, oesophagus, pharynx, and larynx are sometimes affected.

Skin lesions

The lesions might be confined to a small or large section of skin. Patients often get soft blisters on regular or red skin. These blisters break easily, causing painful sores that may bleed. The most common areas affected are the scalp, face, groin, trunk, and armpits.

Crusts encapsulate the break-outs and do not get better. The scalp and face get abraded with crusts and scaly plaques, and the disease may advance to alopecia. Other problems include abnormal nail growth, infections, bleeding, foot ulcers, skin rash, and swollen tongue.

Pemphigus vegetans

Pemphigus vegetans is an uncommon variant of PV. It causes plaques with lots of tissue and crusts. These mainly appear in skin folds, the face, and the scalp. In this variant, oral structures are often affected. Verrucous plaques on the lips' vermillion border and the mouth's side are also seen. Pemphigus vegetans is of two types:

1. The Neumann type is a severe condition that starts with blisters and sores. These sores burst and become significant erosions. Eventually, they turn into oozing masses³
2. Pemphigus vegetans have a milder form called the Hallopeau type. It begins with pustules that burst and become erosions³

Neonatal pemphigus

Around 30% to 45% of babies born to PV carriers get neonatal pemphigus. It's temporary and shows up as vesicles, blisters, and erosions. The mucous membranes are sometimes affected but go away within three weeks. It happens because the transferred antibodies slowly disappear.⁴

Diagnosis

Accurate diagnosis relies entirely on checking the patient's skin and mucous membranes. We need their entire medical history to understand a patient's condition and plan further investigations.⁵

Clinical presentation

• PV includes the oral mucosa in most cases, along with painful erosions and skin lesions with oral blisters
• Check for the Nikolsky sign –blister formation with minor pressure is a typical feature
• Check for skin lesions – the face, trunk, groin, palms and soles
• Alopecia may be present
• Check for the presence of urticarial plaques

Investigations

Tzanck smear (cytological examination)

This is used to demonstrate the cellular features of pemphigus vulgaris.

Histopathological examination

• Assesses blister cleavage level to diagnose PV and differentiate from other bullous lesions
• Biopsy of a recent blister or perilesional area

Direct immunofluorescence examination (DIF)

• To confirm in vitro antigen-antibody reaction
• Recognises certain autoantibodies against keratinocyte (skin cell) cell surfaces
• The gold standard for differential diagnosis of PV

Indirect immunofluorescence examination (IIF)

• Searches for circulating autoantibodies
• Helps in the differential diagnosis of pemphigus foliaceus (PF)

Immunohistochemical examination

• Binds immunological and histological methods for antigen detection
• Detects intercellular markers in PV

Serological diagnosis

ELISA (Enzyme-Linked Immunosorbent Assay):

• Very sensitive and specific method
• Detects autoantibodies
• Useful for patient follow-up

Treatment and management 

Systemic medications and assessment before treatment

Oral or intravenous medications are used to treat autoimmune conditions like pemphigus vulgaris (PV) and treatment should be started early for disease remission, often spanning 5 to 10 years. Clinical assessment is performed to measure weight, height, and blood pressure; laboratory tests encompass blood count, electrolytes, hepatic and renal function, glycemia, vitamin D, lipids, and serology for various infections. ophthalmologic/ Eye evaluation should be done at the start and annually.^6,7

Medications and therapy

Corticosteroids

Prednisone, prednisolone, and deflazacort are commonly used for their anti-inflammatory and immunosuppressive properties. PV improves quickly in a few days. It takes about two months to heal fully and the dose is reduced upon control of the condition.

Intermittent therapy

Administered when control with prednisone above 1 mg/kg/day is challenging. The drugs methylprednisolone and dexamethasone are taken for three days in a row, which helps to lower the dose of prednisone more quickly.

Other medications

These are employed when corticosteroids alone are insufficient or contraindicated.^6,8 Examples include azathioprine, rituximab, cyclophosphamide, methotrexate, dapsone, and cyclosporine.

Intravenous human immunoglobulin (IVIG)

Derived from donors, IVIG removes pathogenic antibodies and affects immune functions. It is used in PV unresponsive to other treatments, with demonstrated efficacy.

Anti-TNF drugs

Tumour necrosis factors (TNF) are proteins released by inflammatory cells and play an important role in causing symptoms of autoimmune conditions. Some reports depict efficacy with anti-TNF drugs like infliximab and etanercept in PV.

Plasmapheresis/immunoadsorption

Plasmapheresis removes pathogenic autoantibodies but may trigger rebound effects.

Additional antibiotic therapy

When there is a secondary infection with clinical or laboratory findings, we rely on culture and antibiogram to guide treatment.

Topical treatment

The goal is to improve systemic therapy by reducing pain and safeguarding from secondary infection; corticosteroids, tacrolimus, antiseptic and antibiotic creams are used. 

Treatment discontinuation

Treatment is discontinued precautiously whilst avoiding premature cessation.¹

Risk factors 

• This condition prevails in certain races like Indians, Southeast Europeans, and people of Jewish or Mediterranean background
• People with autoimmune disorders are susceptible to PV 
• The disease occurs in both genders equally and basically in middle-aged and older individuals

Complications 

• Side effects such as high blood sugar, trouble sleeping, increased appetite, and high blood pressure may occur
• Swelling, weakened adrenal glands, eye problems, and slower healing
• Secondary infections (eg sepsis)
• Undernourishment may cause difficulty in eating
• Death may occur in cases of negligence or no treatment²

FAQs

How can I prevent pemphigus vulgaris?

We cannot prevent pemphigus vulgaris because its cause is unknown. Yet, effective treatment is available to ease symptoms.

How common is pemphigus vulgaris?

Pemphigus vulgaris is a sporadic condition. It is prevalent in ages 50 and 60, affecting both genders evenly.²

Is pemphigus vulgaris contagious?

No. Pemphigus is not contagious.²

What can I expect if I have pemphigus vulgaris?

People suffering from pemphigus can have a normal life with medications and therapy, but it can be devastating without it.

When should I see a doctor?

If you have a painful blister on your skin or mucous membranes that won't heal, contact your doctor right away.

Summary

PV is a skin disease that mostly affects middle-aged and older people. The immune system attacks healthy cells, causing painful blisters on body parts like the mouth, lips, and scalp. The exact cause of it is unknown. It can develop due to autoimmune disorders, certain medications, genetics, tumours, or certain ethnic backgrounds. 

Timely and accurate diagnosis involves clinical presentation, various examinations, and differential considerations. Treatment primarily relies on systemic medications, including corticosteroids, immunosuppressants, and other therapeutic approaches. If PV is not taken care of properly, it can lead to serious issues such as infections, undernourishment, skin problems, and even death. Managing this condition requires regular check-ins and a good understanding of risk factors.