Derm Dx: Progressive generalized blisters

Pemphigus skin diseases are a group of autoimmune conditions characterized by autoantibodies against desmoglein, the primary component of desmosomes responsible for cell-to-cell adhesion in skin. This patient was diagnosed with pemphigus foliaceus (PF), a subtype of pemphigus with features including...

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Pemphigus skin diseases are a group of autoimmune conditions characterized by autoantibodies against desmoglein, the primary component of desmosomes responsible for cell-to-cell adhesion in skin.

This patient was diagnosed with pemphigus foliaceus (PF), a subtype of pemphigus with features including flaccid bullae and localized or generalized exfoliation.

The lack of clinically apparent mucosal involvement, even in patients with widespread disease, helps distinguish PF from pemphigus vulgaris (PV), a more common subtype of pemphigus. PF most commonly presents in both men and women equally between the ages of 50 and 60 years.

PF begins subtly with a few scattered, transient and crusted lesions forming after the bullae have ruptured. These initial lesions are often mistaken for impetigo, because they have a seborrheic distribution that includes the face, scalp and upper trunk.

The initial vesicles/bullae that appear are flaccid and superficial. After the bullae rupture, patients tend to present with scaly, crusted, cutaneous erosions on an erythematous base. In most cases, the disease stays localized for years, but PF may also rapidly progress to generalized involvement.

Patients with PF have a positive Nikolsky’s sign, where tangential pressure on skin causes superficial epidermal loss. Unlike PV, PF does not affect the mucous membranes. Also unlike PV, patients with PF are not severely ill, though they may report pain, burning or pruritus in association with the skin lesions.

PF lesions may develop secondary infection; therefore, the presence of bacteria in the lesions does not rule out PF or confirm bullous impetigo. PF may also be drug-induced, so a complete review of a patient’s medications is necessary.

On histology, the hallmark of PF is the finding of IgG autoantibodies against the cell surface of keratinocytes, the predominant cell type in the epithelial layer of the skin. Acantholysis, or loss of intercellular connections between keratinocytes, occuring in the upper epidermis within the granular layer is a key finding in PF. The deeper epidermis remains intact. The stratum corneum, the most superficial layer of the epidermis, may be missing completely.

Because blisters are superficial and fragile, adequate samples from intact lesions may be difficult to obtain. Acute inflammatory cells are found in the blisters, with eosinophils in the dermis.

PF can be diagnosed by demonstrating specific desmoglein-1 (DSG1) IgG autoantibodies against cell surface of keratinocytes. IgG deposition is seen in 100% of patients with PF. The deposits are found throughout the epidermis, though they may be more prominent in the upper epidermis.

ELISA can be used to confirm the diagnosis by detecting DSG1 antibodies in the serum. These autoantibodies induce a loss of cell adhesions between keratinocytes resulting in blister formation. PF autoantibodies target DSG1 while PV autoantibody targets both DSG1 and DSG3.

To distinguish between subtypes of pemphigus, especially PV and PF, clinicians may look at the DSG found in serum. In PV and its subtypes, DSG3 is positive with DSG1 being variable. In PF, DSG1 is positive whereas DSG3 is negative.

PF has a better prognosis than PV. If PF is localized, potent topical corticosteroids may be sufficient to control the disease.

In more advanced cases, tapered systemic corticosteroids are the gold standard, but high dose intravenous immunoglobulin, plasmapheresis, etanercept and rituximab are other new treatment options.

Once a patient achieves remission, monitoring circulating autoantibody titers can aid in adjusting prednisone doses. Azathioprine, mycophenolate and cyclophosphamide have also shown promise when used in conjunction with prednisone.

Christopher Chu, BS, is a medical student at Baylor College of Medicine.  

Adam Rees, MD, is a graduate of the University of California Los Angeles School of Medicine and a resident in the Department of Dermatology at Baylor College of Medicine also in Houston.