Pemphigus Vulgaris
Summary
Pemphigus Vulgaris (PV) is a potentially life-threatening autoimmune blistering disease characterised by flaccid blisters and erosions on the skin and mucous membranes. It is caused by IgG autoantibodies targeting Desmoglein 3 (and 1), causing loss of adhesion between keratinocytes (Acantholysis). Unlike Bullous Pemphigoid, the blisters are superficial (intra-epidermal) and rupture easily, often leaving large, painful, raw areas that are prone to infection. [1,2]
Clinical Pearls
Pemphigus means "Bubble": From the Greek pemphix.
The "Asboe-Hansen" Sign: If you press on the roof of a blister, the fluid dissects laterally into the surrounding seemingly normal skin, extending the blister size. This demonstrates the lack of cohesion in the epidermis.
Paraneoplastic Pemphigus: A severe variant associated with underlying malignancy (Non-Hodgkin Lymphoma, CLL). Suspect this if the stomatitis is exceptionally severe and refractory.
Demographics
- Incidence: Rare (0.1 - 0.5 per 100,000).
- Age: 40-60 years (Younger than Pemphigoid).
- Ethnicity: Higher prevalence in Ashkenazi Jews, Mediterranean, and Indian populations (HLA-DR4/DR14 associations).
The "Glue" Failure
- Target: Desmosomes are the "spot welds" that hold skin cells (keratinocytes) together.
- Antibody: IgG autoantibodies bind to Desmoglein 3 (mucola/lower epidermis) and Desmoglein 1 (superficial epidermis).
- Mucosal Dominant PV: Anti-Dsg3 only.
- Mucocutaneous PV: Anti-Dsg3 + Anti-Dsg1.
- Acantholysis: The cells fall apart ("Acantholysis"). The basement membrane remains intact (unlike Pemphigoid), so the "floor" of the blister is the basal cell layer.
Mucosal (Start)
Cutaneous (Later)
Signs
- Nikolsky Sign Positive: Firm sliding pressure with a finger on normal-appearing skin causes the epidermis to shear off (indicating acantholysis).
- Crusting: large painful crusted areas.
Biopsy (Two Samples Needed)
- Lesional Skin (H&E):
- Intra-epidermal split (Suprabasal).
- Acantholysis: "Free-floating" rounded keratinocytes in the blister fluid.
- Row of Tombstones: The basal layer remains attached to the basement membrane.
- Perilesional Skin (DIF):
- Direct Immunofluorescence: IgG (and C3) deposition in a "Chicken Wire" or "Intercellular" pattern surrounding the keratinocytes.
Bloods
- ELISA: Detects Anti-Desmoglein 1 and 3 antibodies. Titre correlates with disease activity.
Management Algorithm
PEMPHIGUS VULGARIS DIAGNOSED
(Con rmed by Biopsy/DIF)
↓
INITIAL STABILISATION
- If extensive erosions -> Admit (Burn protocols)
- Fluid balance / Infection control
- Oral hygiene (viscous lidocaine/antiseptics)
↓
INDUCTION THERAPY (Remission)
• **Corticosteroids** (High Dose)
- Prednisolone 1mg/kg/day
- Taper slowly once controlled
+ PLUS +
• **Rituximab** (First Line Biological)
- Anti-CD20 monoclonal antibody
- Superior to Mycophenolate (Ritux 3 Trial)
↓
MAINTENANCE THERAPY
- Aim to wean steroids
- Maintenance Rituximab infusions
- Or Azathioprine / Mycophenolate Mofetil
Rituximab Revolution
- Traditionally, PV was treated with high dose steroids and Azathioprine.
- The Ritux 3 Trial (Lancet 2017) showed Rituximab was significantly more effective, with higher cure rates and lower steroid requirements. It is now first-line in many guidelines.
- Sepsis: Loss of skin barrier -> Staph aureus infection. (Significant cause of mortality historically).
- Dehydration / Electrolyte Imbalance.
- Steroid Side Effects: Diabetes, Osteoporosis (Provide Bisphosphonates).
- Without treatment: Nearly 100% fatal (Sepsis/Dehydration).
- With treatment: Mortality 5-10% (mostly treatment complications).
- Remission: Can be achieved, but relapse is common. Often lifelong monitoring needed.
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| Pemphigus | BAD (2017) | Rituximab as an option. Biopsy protocols. |
| Pemphigus | EADV (European) | Rituximab first line for moderate/severe. |
Landmark Evidence
1. Ritux 3 Trial (Joly et al, Lancet 2017)
- Defined the modern standard of care. showed 89% remission with Rituximab vs 34% with Steroids alone.
What is Pemphigus?
It is a serious condition where your immune system attacks the "glue" that holds your skin cells together. Because the cells can't stick to each other, the skin becomes incredibly fragile and blisters with the slightest rub.
Is it different from other blister conditions?
Yes. Unlike "Pemphigoid" (which is deeper and less fragile), Pemphigus causes very thin blisters that break immediately, leaving large, painful raw sores. It often starts in the mouth.
Treatment
We need to switch off the immune system's attack. We use strong steroids initially, but the best treatment is a "smart bomb" drug called Rituximab (given by a drip) which specifically removes the immune cells making the bad antibodies. It can put the disease into long-term sleep (remission).
Primary Sources
- Harman KE, et al. British Association of Dermatologists' guidelines for the management of pemphigus vulgaris. Br J Dermatol. 2017.
- Joly P, et al. First-line rituximab combined with short-term prednisone versus prednisone alone for the treatment of pemphigus (Ritux 3). Lancet. 2017.
Common Exam Questions
- Differentiator: "Pemphigus vs Pemphigoid?"
- Answer: Pemphigus = Flaccid, Intra-epidermal, Chicken-wire IgG, Desmosomes. Pemphigoid = Tense, Sub-epidermal, Linear IgG, Hemidesmosomes.
- Sign: "Nikolsky Sign?"
- Answer: Positive in Pemphigus.
- Target: "Auto-antigen?"
- Answer: Desmoglein 3.
- Histology: "Acantholysis?"
- Answer: Loss of keratinocyte adhesion.
Viva Points
- Why Mouth First?: Desmoglein 3 is the main adhesion in mucosa. Desmoglein 1 is more in skin. So antibodies to Dsg3 cause mouth ulcers. As Dsg1 antibodies develop, skin gets involved.
- Row of Tombstones: The basal layer stays attached because Hemidesmosomes (which attach to the bottom) are NOT affected. Only the Desmosomes (side-to-side attachment) are destroyed.
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.