Pemphigus

Essentials of Diagnosis

• Relapsing crops of skin bullae

• Often preceded by mucous membrane bullae, erosions, and ulcerations

• Superficial detachment of the skin after pressure or trauma variably present (Nikolsky sign)

• Acantholysis on biopsy

• Immunofluorescence studies and serum ELISA for pathogenic antibodies are confirmatory

General Considerations

• Pemphigus is an uncommon intraepidermal blistering disease occurring on skin and mucous membranes

• Caused by autoantibodies to adhesion molecules expressed in the skin and mucous membranes

• There are several forms of pemphigus

  • Pemphigus vulgaris and its variant, pemphigus vegetans

  • Pemphigus foliaceus, which is more superficially blistering, and its variant, pemphigus erythematosus

  • Paraneoplastic pemphigus

• The vulgaris form begins in the mouth in over 50% of cases

• The foliaceus form is especially apt to be associated with other autoimmune diseases, or it may be drug-induced

• Paraneoplastic pemphigus, a unique form of the disorder, is associated with numerous types of benign and malignant neoplasms but most frequently non-Hodgkin lymphoma

Demographics

• All forms may occur at any age but most commonly in middle age

Symptoms and Signs

• An insidious onset of flaccid bullae, crusts, and erosions in crops or waves

• The bullae appear spontaneously and are tender and painful when they rupture

• In pemphigus vulgaris, lesions often appear first on the oral mucous membranes, and these rapidly become erosive

• The scalp is another site of early involvement

• Rubbing a cotton swab or finger laterally on the surface of uninvolved skin may cause easy separation of the epidermis (Nikolsky sign)

• Downward pressure on a fresh bulla may cause lateral spread (Asboe-Hansen sign)

• Pemphigus vegetans presents as erosive vegetating plaques, most often in intretriginous areas

• Pemphigus foliaceus

  • A superficial form of pemphigus where cutaneous lesions often present as flaccid bullae that quickly evolve into superficial erosions and thin pink plaques with overlying scale

  • Mucosal lesions are rare

• Pemphigus erythematosus

  • Has overlapping features of pemphigus foliaceus and lupus erythematosus

  • Presents with flaccid bullae that develop overlying scale and crust in a photodistributed area

  • Mucosal lesions are rare

• Paraneoplastic pemphigus

  • Histologically and immunologically distinct from other forms

  • Oral lesions predominate

  • Cutaneous erythematous plaques resembling erythema multiforme are characteristic

  • Survival rates are low because of the underlying malignancy

Differential Diagnosis

• Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis

• Drug eruptions

• Bullous impetigo

• Contact dermatitis

• Dermatitis herpetiformis

• Bullous pemphigoid

• Subacute cutaneous lupus erythematosus

Laboratory Tests

• The diagnosis is made by light microscopy and by direct and indirect immunofluorescence microscopy

• Autoantibodies to intercellular adhesion molecules can be detected with ELISA assays

Medications

• See Table 6–2

• Local measures

  • In patients with limited disease, skin and mucous membrane lesions should be treated with topical corticosteroids

  • Complicating infection requires appropriate systemic and local antibiotic therapy

• Systemic measures

  • Initial therapy is with systemic corticosteroids: prednisone, 60–80 mg orally daily

  • In all but the most mild cases, a steroid-sparing agent is added from the beginning, since the course of the disease is long and the steroid-sparing agents take several weeks to exert their activity

  • Traditionally, azathioprine (100–200 mg orally daily) or mycophenolate mofetil (1–1.5 g orally twice daily) were used

  • Rituximab (1 g intravenously on days 1 and 15 as induction therapy followed by 500 mg intravenously every 6 months as maintenance therapy)

    • FDA approved for the treatment of pemphigus vulgaris

    • Associated with therapeutic induction of a complete remission

    • Considered to be first-line therapy by many experts

    • Repeated courses are efficacious and well tolerated in patients who do not achieve complete remission or relapse

  • Other anti-CD20 antibody therapies (eg, ofatumumab)

    • Have been shown to be effective in case reports

    • May be future therapeutic options

  • In refractory cases, monthly IVIG (2 g/kg intravenously over 3–4 days,) pulse intravenous corticosteroids, cyclophosphamide or plasmapheresis can be used

Therapeutic Procedures

• When the disease is severe, hospitalize the patient at bed rest and provide antibiotics and intravenous feedings as indicated

• Anesthetic troches used before eating ease pain from oral lesions

Complications

• Secondary infection is a major cause of morbidity and mortality

• Disturbances of fluid, electrolyte, and nutritional intake can occur as a result of painful oral ulcers

Prognosis

• The course tends to be chronic in most patients, though some appear to experience remission

• Infection is the most frequent cause of death, usually from Staphylococcus aureus septicemia

When to Refer

• If there is a question about the diagnosis, if recommended therapy is ineffective, or if specialized treatment is necessary

When to Admit

• For severe disease