CASE #1: Pemphigus vulgaris

An autoimmune blistering disease of the mucous membranes and skin, pemphigus vulgaris (PV) derives its name from the Greek word, pemphix, for blister.1 PV is characteristically seen in older patients; the median age of onset is 50-60 years. Men and women are affected in approximately equal numbers. The incidence of the disease is variable, with estimates ranging from 0.076 per 100,000 in Finland to 1.61 per 100,000 in Jerusalem.2

PV is caused by IgG autoantibodies directed at the cell surface of keratinocytes. These antibodies bind to desmoglein 3, a component of the desmosome, which is a vital structure for cell-cell adhesion in the skin and mucous membranes.3 This disruption of the desmosomes leads to dysadhesion and the typical clinical findings of flaccid bullae and cutaneous erosions.

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Nearly all patients with PV will develop painful oral erosions, most commonly of the buccal and palatine mucosa. The pain may lead to decreased oral intake. Other mucosal areas, such as the conjunctiva, nasal mucosa, and genitals, may also be affected. More than 50% of PV patients have skin involvement. The characteristic cutaneous findings are flaccid blisters on normal to erythematous skin. Bullae are rarely found intact because they rupture easily. The resulting erosions are often painful and heal poorly. Lateral spread of the bullae with slight pressure, also known as the Nikolsky sign, is characteristic. The Nikolsky sign is not specific for PV, however, as it may be seen in other blistering conditions, such as toxic epidermal necrolysis.

Histologically, PV shows intraepidermal blister formation and suprabasilar acantholysis without keratinocyte necrosis. Because the hemidesmosomal attachments with the basement membrane are preserved, keratinocytes remain at the base of the epidermis. Their appearance resembles a “row of tombstones,” a commonly described finding on pathology. An inflammatory infiltrate of eosinophils may be seen within the blister cavity and upper dermis. DIF of perilesional normal skin will show IgG deposition around the surface of keratinocytes.

Distinguishing PV from other vesiculobullous diseases can be challenging. When blisters are confined to the mucosa, PV can resemble herpes stomatitis, aphthous stomatitis, erythema multiforme, lichen planus, and cicatricial pemphigoid. For cutaneous lesions, the differential diagnosis includes other forms of pemphigus, bullous pemphigoid, erythema multiforme, Hailey-Hailey disease, and linear IgA bullous dermatoses.

Without treatment, PV is associated with an extremely high mortality resulting from extensive loss of the epidermal skin barrier. Such exposure can lead to metabolic losses and secondary bacterial infections. Even with treatment, the morbidity and mortality of PV is significant.4 Systemic corticosteroids are the mainstay of treatment for PV today.5 Prednisone 1 mg/kg/day is the typical starting dose. Because corticosteroids have significant side effects, especially at high doses, other immunosuppressive agents, such as azathioprine, cyclophosphamide, and mycophenolate mofetil, have been used. In addition to their steroid-sparing effect, these agents may result in better disease control.6 Recently, reports of rituximab, an anti-CD20 monoclonal antibody, and high-dose IV immunoglobulin have shown some promise in patients with steroid-resistant PV.7,8

This patient experienced significant improvement with an initial regimen of prednisone and azathioprine. Later, she was maintained on azathioprine to maintain control of her disease as the corticosteroids were tapered.