Pemphigus



Patient Story





A young man presented with painful blisters on his face and mouth (Figure 185-1). The patient was referred to dermatology that day. The dermatologist recognized likely pemphigus vulgaris (PV) and did shave biopsies for histopathology and direct immunofluorescence of facial vesicles/bullae to confirm the presumed diagnosis. The patient was started on 60 mg of prednisone daily until the pathology confirmed PV. Steroid-sparing therapy was then discussed and started in 2 weeks from presentation.







Figure 185-1



Pemphigus vulgaris on the face of a young man with mouth involvement. (Courtesy of Eric Kraus, MD.)







Introduction





Pemphigus is a rare group of autoimmune bullous diseases of skin and mucous membranes characterized by flaccid bulla and erosions. The three main types of pemphigus are PV (with the pemphigus vegetans variant), pemphigus foliaceous (with the pemphigus erythematosus variant), and paraneoplastic pemphigus. All types of pemphigus cause significant morbidity and mortality. Although pemphigus is not curable, it can be controlled with systemic steroids and immunosuppressive medications. These medications can be lifesaving, but also place pemphigus patients at risk for a number of complications. The word pemphigus is derived from the Greek word pemphix, which means bubble or blister.






Epidemiology





Epidemiology of the three major types of pemphigus:







  • PV (Figures 185-1, 185-2, 185-3, and 185-4):

    • Most common form of pemphigus in the United States.
    • Annual incidence is 0.75 to 5 cases per 1 million population.1
    • Usually occurs between 30 and 50 years of age.2
    • Increased incidence in Ashkenazi Jews and persons of Mediterranean origin.2
    • Pemphigus vegetans is a variant form of PV (Figures 185-5 and 185-6).

  • Pemphigus foliaceus (PF) (Figures 185-7, 185-8, 185-9, and 185-10): Superficial form of pemphigus.

    • More prevalent in Africa (Figures 185-11 and 185-12).1
    • Variant forms include pemphigus erythematosus (resembles the malar rash of lupus erythematosus) and fogo selvagem.
    • Fogo selvagem is an endemic form of PF seen in Brazil and affects teenagers and individuals in their twenties.1

  • Paraneoplastic pemphigus (PNP)

    • Onset at age 60 years and older.
    • Associated with occult neoplasms commonly lymphoreticular.
    • Malignancies like non-Hodgkin lymphoma and chronic lymphocytic leukemia.
    • Also associated with benign neoplasms such as thymoma and Castleman disease (angiofollicular lymph node hyperplasia).2







Figure 185-2



Pemphigus vulgaris on the back with crusted and intact bullae. Downward pressure on a bulla demonstrates a positive Asboe-Hansen sign with lateral spread of a fresh bullae. (Courtesy of Eric Kraus, MD.)








Figure 185-3



Pemphigus vulgaris involving the lips and palate of a 55-year-old woman. (Courtesy of Dan Shaked, MD.)








Figure 185-4



Severe fatal pemphigus vulgaris. (Courtesy of Eric Kraus, MD.)








Figure 185-5



Pemphigus vegetans in the groin of a middle-aged woman. (Courtesy of Eric Kraus, MD.)








Figure 185-6



Pemphigus vegetans widespread over the external genitalia and buttocks. (Courtesy of Eric Kraus, MD.)








Figure 185-7



Pemphigus foliaceous on the face of a black man. (Courtesy of Jack Resneck, Sr., MD.)








Figure 185-8



Pemphigus foliaceous on the back of a 55-year-old Hispanic woman. Note the absence of bulla and the corn flake crusting from the superficial erosions. (Courtesy of Richard P. Usatine, MD.)








Figure 185-9



Pemphigus foliaceous with large erosions on the back and extremities of this patient. (Courtesy of Eric Kraus, MD.)








Figure 185-10



Widespread pemphigus foliaceous. (Courtesy of Eric Kraus, MD.)








Figure 185-11



Pemphigus foliaceous on the trunk and arms of a woman in Africa. Some of the lesions appear annular but they are all superficial erosions within the epidermis. (Courtesy of Richard P. Usatine, MD.)








Figure 185-12



Another case of pemphigus foliaceous in Africa. Pemphigus foliaceous is more prevalent in Africa. Note the hyperpigmentation of the healing lesions after treatment has begun. (Courtesy of Richard P. Usatine, MD.)







Etiology and Pathophysiology






  • The basic abnormality in all three types of pemphigus is acantholysis, a process of separating keratinocytes from one another. This occurs as a result of autoantibody formation against desmoglein (the adhesive molecule that holds epidermal cells together). Separation of epidermal cells leads to formation of intraepidermal clefts, which enlarge to form bullae.1
  • The mechanism that induces the production of these autoantibodies in most individuals is unknown. Yet PF may be triggered by drugs, most commonly thiol compounds like penicillamine, captopril, piroxicam, and others, like penicillin and imiquimod.3 An environmental trigger in the presence of susceptible human leukocyte antigen (HLA) gene is suggested to induce autoantibodies in fogo selvagum.1
  • The autoantibodies in pemphigus are usually directed against desmoglein 1 and 3 molecules (Dsg1 and Dsg3). Dsg1 is present predominantly in the superficial layers of the epidermis, whereas Dsg3 is expressed in deeper epidermal layers and in mucous membranes. As a result, clinical presentation depends on the antibody profile. In PV, a limited mucosal disease occurs when only anti-Dsg3 antibody is present, but extensive mucosal and cutaneous disease occurs when both anti-Dsg1 and Dsg3 antibodies are present. In PF, mucosal lesions are absent and the cutaneous lesions are superficial because of isolated anti-Dsg1 antibody.
  • Patients with PNP demonstrate both anti-Dsg1 and Dsg3 antibodies. However, unlike PV, autoantibodies against plakin proteins (another adhesive molecule) are also observed in patients with PNP and these autoantibodies form a reliable marker for this type of pemphigus.






Diagnosis





Clinical Features



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Jun 5, 2016 | Posted by in GENERAL & FAMILY MEDICINE | Comments Off on Pemphigus

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