Pemphigus

Last reviewed: 28 Aug 2022

Last updated: 13 Aug 2021

Pemphigus encompasses a group of potentially life-threatening autoimmune bullous diseases characterized by blisters and erosions of the mucous membranes and skin.

Pemphigus vulgaris (PV) is the most common variant and affects skin and mucosa.

Pemphigus foliaceus (PF) is confined to the skin. Paraneoplastic pemphigus (PNP) is rare; it can involve the skin and mucosal surfaces of the eyes, mouth, nasopharynx, and esophagus.

Diagnosis is based on clinical findings of erosions (epidermal loss) and blisters of the skin, mucosa, or both.

Direct immunofluorescence staining of biopsied skin shows immunoglobulin and C3 deposits on the keratinocyte surface, and histology reveals keratinocyte acantholysis.

Treatment aims to reduce or eliminate pathologic autoantibodies and consists of long-term immunosuppressive therapy.

Definition

Pemphigus describes a group of autoimmune blistering diseases that involve the epidermal surfaces of the skin, mucosa, or both. There are three broad categories: pemphigus vulgaris (PV), pemphigus foliaceus (PF), and paraneoplastic pemphigus (PNP).

Underlying intraepithelial blister formation is caused by IgG autoantibodies against desmoglein 3 (Dsg3) and/or desmoglein 1 (Dsg1) on the cell surface of epidermal keratinocytes.[1]

Pemphigus is associated with pain and impaired sleep. Swallowing difficulties are present if there is esophageal involvement. It is associated with increased rates of depression.[2]

History and exam

Key diagnostic factors

chronic erosive blistering of the skin, mucosa, or both
chronic mouth erosions (PV, PNP)
painful lips (PNP)
shortness of breath (PNP)

More key diagnostic factors

Other diagnostic factors

pruritic scalp (PV, PF)
bloody nose (PV, PNP)
painful skin (PV, PF, PNP)
dysphagia (PV)
pruritic skin (PV, PF)
conjunctivitis (PV, PNP)

Other diagnostic factors

Risk factors

increasing age
HLA DR4 (PV)
HLA DQ1 (PV)
HLA DRB1 (PNP)
associated malignancy (PNP)
D-penicillamine
ACE inhibitors
penicillin
thiopronine
interleukin 2
nifedipine
rifampin
exposure to hematophagous insects

More risk factors

Diagnostic investigations

1st investigations to order

skin biopsy, hematoxylin and eosin stain
skin biopsy, direct immunofluorescence

More 1st investigations to order

Investigations to consider

indirect immunofluorescence on serum
serum ELISA
upper gastrointestinal endoscopy
CXR
chest CT scan
PFT
serum immunoblot (Western blot)

More investigations to consider

Treatment algorithm

ACUTE

mild pemphigus vulgaris

mild pemphigus foliaceus

moderate to severe pemphigus vulgaris or pemphigus foliaceus

paraneoplastic pemphigus

ONGOING

moderate to severe pemphigus vulgaris or pemphigus foliaceus 6 months after initial therapy: with disease control/complete remission

moderate to severe pemphigus vulgaris or pemphigus foliaceus 6 months after initial therapy: without complete remission

moderate to severe pemphigus vulgaris or pemphigus foliaceus 12 to 18 months after initial therapy: complete remission

severe/refractory pemphigus

Contributors

Authors

Jon H. Meyerle, MD

Associate Professor

Department of Dermatology

Uniformed Services University of the Health Sciences

Bethesda

Disclosures

JHM declares that he has no competing interests.

Grant J. Anhalt, MD

Professor

Department of Dermatology

Johns Hopkins Medical Institution

Baltimore

Disclosures

GJA is a consultant for Janssen on a clinical trial design for an investigational drug for bullous pemphigoid.

Peer reviewers

Daniel Mimouni, MD

Professor

Department of Dermatology

Rabin Medical Center

Petah Tikva

Israel

Disclosures

DM declares that he has no competing interests.

Vesna Petronic-Rosic, MD, MSc

Associate Professor and Clinical Director

Section of Dermatology

University of Chicago

Chicago

Disclosures

VPR declares that she has no competing interests.

Timothy Patton, MD

Assistant Professor of Dermatology

Department of Dermatology

University of Pittsburgh

Pittsburgh

Disclosures

TP declares that he has no competing interests.

Differentials
- Familial benign pemphigus (Hailey-Hailey disease)
- Bullous pemphigoid (BP)
- Linear IgA bullous dermatosis
More Differentials
Guidelines
- Updated S2K guidelines on the management of pemphigus vulgaris and foliaceus initiated by the European Academy of Dermatology and Venereology (EADV)
- Diagnosis and management of pemphigus: recommendations by an international panel of experts
More Guidelines
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Pemphigus

Summary

Definition

History and exam

Key diagnostic factors

Other diagnostic factors

Risk factors

Diagnostic investigations

1st investigations to order

Investigations to consider

Treatment algorithm

mild pemphigus vulgaris

mild pemphigus foliaceus

moderate to severe pemphigus vulgaris or pemphigus foliaceus

paraneoplastic pemphigus

moderate to severe pemphigus vulgaris or pemphigus foliaceus 6 months after initial therapy: with disease control/complete remission

moderate to severe pemphigus vulgaris or pemphigus foliaceus 6 months after initial therapy: without complete remission

moderate to severe pemphigus vulgaris or pemphigus foliaceus 12 to 18 months after initial therapy: complete remission

severe/refractory pemphigus

Contributors

Authors

Jon H. Meyerle, MD

Disclosures

Grant J. Anhalt, MD

Disclosures

Peer reviewers

Daniel Mimouni, MD

Disclosures

Vesna Petronic-Rosic, MD, MSc

Disclosures

Timothy Patton, MD

Disclosures

Differentials

Guidelines

Log in or subscribe to access all of BMJ Best Practice

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