Clinical Dermatology

Diagnostic Hallmarks

1. Distribution: often starts on the extremities but becomes generalized fairly quickly
2. Tense, tough blisters usually arising from normal skin
3. Individual lesions heal spontaneously while new blisters continue to appear
4. Immunofluorescent studies: IgG and C3 in a linear pattern at the dermal-epidermal junction.
   

   Clinical Presentation

   Patients with pemphigoid characteristically develop the disease after the age of 60. Crops of large bullae, 2-5 cm in diameter, appear first on the extremities but within a short period of time begin to develop on the trunk as well. Occasionally blisters are also seen on the scalp, palms, soles, and oral mucous membranes.

   In most instances the bullae arise from normal-appearing skin but some often develop on an erythematous background. When lesions of this latter type predominate, distinction from bullous erythema multiforme, paraneoplastic pemphigus, or dermatitis herpetiformis may be difficult. The blisters, unlike those of pemphigus, are histologically located in a subepidermal location. For this reason the roofs are not easily broken and the bullae usually stay intact for many days. Thus, as a general rule, intact blisters outnumber erosions whereas the reverse is true in pemphigus.

   The bullae are usually filled with clear fluid but occasionally some are tinged with blood. Old lesions heal as rapidly as new lesions appear. For this reason there is much less debilitation than is seen in patients with pemphigus. Some patients are completely asymptomatic but itching often is present and occasionally it is very severe.

   A clinical diagnosis must be confirmed by biopsy. Light microscopy reveals a subepidermal blister with a perilesional inflammatory infiltrate containing a large number of eosinophils. At the electron microscopic level the split appears to occur within the lamina lucida portion of the basement membrane zone. Biopsies of perilesional skin for direct immunofluorescence reveal a band of immunoglobulin and the C3 component of complement at the dermal-epidermal junction.

   

   The immunoglobulin deposited is usually IgG, but in a small percentage of cases, other immunoglobulins are found instead. Approximately 80% of patients will also have circulating autoantibodies directed at antigens within the basement membrane zone. These can be demonstrated with indirect immunofluorescent studies .

   Pemphigoid Variants. Linear IgA bullous disease of adults (IgA pemphigoid) is very similar clinically to pemphigoid though often the blisters are smaller in size. Some authorities consider this disease as a variant of dermatitis herpetiformis but other than its responsiveness to dapsone therapy the two diseases have little in common. Cicatricial pemphigoid is a rare disease in which erosive disease of mucosal surfaces (particularly the eyes and the mouth) is followed by scarring. Cutaneous bullae are not prominent but when they occur they too may heal with scarring.

   Course and Prognosis

   Pemphigoid is a chronic disease which persists indefinitely. New lesions develop as rapidly as old lesions heal such that 10-20% of the skin surface is continually involved. Debilitation due to the disease itself is not great but it is additive to the effects of advanced age and other intercurrent disease. Death due to superimposed infection or to toxicity associated with steroid therapy occurs in 5-10% of patients.

   Pathogenesis

   Pemphigoid is an autoimmune disease in which antibodies are directed toward several hemidesmosomal proteins (180 and 230 kD) located within the lamina lucida region of the basement membrane zone. Immunoglobulin and complement components are almost always present at this location, and 80% of patients also have circulating antibodies that fix to the same region. Complement activation is required for blister formation. Model systems for the experimental creation of pemphigoid-type blisters have recently been described.

   Genetic factors seem to be less important than for the other immunobullous diseases. There are no racial or national groups which seem particularly predisposed to the disease and HLA typing has failed to reveal patterns which consistently diner from those of the normal population.

   Therapy

   Systemically administered corticosteroids are usually the treatment of choice for patients with pemphigoid. Initially prednisone is administered in a single morning dose of 60-80 mg. Thereafter, depending on the rapidity of response, the dosage is gradually tapered to a maintenance level of approximately 20-40 mg/day. Occasionally, further tapering (and, sometimes, even discontinuation) of the prednisone is possible, but often at this point it will be appropriate to add a steroid-sparing agent such as azathioprine or cyclophosphamide. Some patients do show a response to dapsone therapy, but the degree of improvement (except in the IgA variant) is usually not great.

This entry was posted on Monday, September 10th, 2007 at 9:46 am and is filed under Vesiculobullous Diseases. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.