Derm Dx: Mouth rash and painful skin blisters

ExplanationPemphigus vulgaris is an autoimmune immunobullous dermatosis. The autoimmune immunobullous dermatoses are a group of diseases in which the patient's body produces antibodies that attack various proteins within the skin, resulting in blistering. In pemphigus vulgaris, the antibodies are primarily...

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Explanation

Pemphigus vulgaris is an autoimmune immunobullous dermatosis. The autoimmune immunobullous dermatoses are a group of diseases in which the patient’s body produces antibodies that attack various proteins within the skin, resulting in blistering. In pemphigus vulgaris, the antibodies are primarily directed at desmoglein-3, which is a protein in the desmosomes. Desmosomes attach the keratinocytes of the epidermis to one another. The desmoglein-3 antibody produced in pemphigus vulgaris essentially attacks the skin and leads to intraepidermal blistering.

Pemphigus vulgaris is rare but occurs more commonly in patients of Jewish descent. Men and women are equally affected, and the onset is generally in the fifth to sixth decade of life.

Vesicles, bullae, and erosions occur on both skin and mucous membranes in pemphigus vulgaris. In the majority of cases, the disease initially appears in the mouth. Oral lesions appear as erosions and may extend to the lips and throat. The oral cavity is malodorous. The ocular, nasal, and anogenital mucosa may also be involved.

Cutaneous disease appears as fragile vesicles and bullae on either normal or erythematous skin. The blisters rupture, forming erosions that heal, leaving hyperpigmentation. The delicate blisters are short-lived. When intact, the blisters demonstrate the Asboe-Hansen sign, in which the application of lateral pressure will force the blister fluid to spread under the adjacent skin. The Nikolsky sign, in which rubbing of the skin causes the epidermis to shear away, may also be present.

Diagnosis

The diagnosis of pemphigus vulgaris is suspected in patients with blistering and erosions of the skin and mucus membranes (especially in the oral cavity). The diagnosis must be confirmed with biopsy and/or direct immunofluorescence, indirect immunofluorescence, or ELISA.

The biopsy demonstrates suprabasilar acantholysis, which means that there is a split within the epidermis above the basal keratinocytes.

Direct immunofluorescence is a technique in which the biopsy is stained to look for the presence of antibodies. In pemphigus vulgaris, there is a chicken-wire pattern of staining, since the desmoglein-3 autoantibodies will be present between the keratinocytes.

Indirect immunofluorescence and ELISA test the patient’s serum for the presence of the autoantibody to desmoglein-3. The ELISA test is 97% sensitive and 98% specific, making this an ideal test when available.

Treatment and prognosis

Prior to the availability of such corticosteroid medications as prednisone, the death rate from pemphigus vulgaris was 90%. Death occurred from infections and fluid, electrolyte, and nutritional imbalances that occurred due to loss of the epidermal barrier. The death rate has lowered dramatically with current therapies. However, there is toxicity associated with these therapies, and a small percentage of patients now die due to the therapy itself. However, since the mortality from nontreatment greatly exceeds the mortality of treatment, patients must be carefully counseled on the risks and benefits. Treatment should be initiated promptly on suspicion or establishment of the diagnosis.

The standard treatment for pemphigus vulgaris is high-dose corticosteroid therapy (e.g., prednisone) paired with an adjunctive steroid-sparing therapy. The disease can generally be controlled after six weeks of steroid therapy initiated at 1 mg/kg of ideal body weight. Once the disease is controlled, the steroids may be slowly tapered, usually by lowering the dose by 25% every four weeks. It may take months to years to completely wean a patient off medication since the disease frequently flares when the steroids are tapered. To help prevent corticosteroid-induced osteoporosis, a bisphosphonate (e.g., alendronate [Binosto, Fosamax]) along with calcium and vitamin D should be initiated. Consider a baseline dual-energy x-ray absorptiometry (DEXA) scan repeated at regular intervals. Perform TB testing within the first several weeks of therapy. Individuals on long-term corticosteroids may develop hypertension, obesity, and cataracts and/or glaucoma, so BP, weight, and ophthalmologic examination should be performed at regular intervals. Potassium, fasting glucose, and fasting triglycerides should also be monitored.

The steroid-sparing agents assist in tapering the corticosteroids. Such agents as azathioprine (Azasan, Imuran) and mycophenolate mofetil (CellCept) are currently the most commonly used steroid-sparing medications and should be initiated early. Intravenous immunoglobulin (IVIG) and rituximab (Rituxan) infusions allow for more rapid corticosteroid tapering and may be useful in leading to clinical remission.

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 in Houston.

References

1. James WD, Berger TD, Elston DM et al. “Chapter 21 – Chronic Blistering Dermatoses.” Andrews’ Diseases of the Skin: Clinical Dermatology. Philadelphia, Pa.: Saunders Elsevier; 2006.

2. Tampoia M, Giavarina D, Di Giorgio C, Bizzaro N. Diagnostic accuracy of enzyme-linked immunosorbent assays (ELISA) to detect anti-skin autoantibodies in autoimmune blistering skin diseases: a systematic review and meta-analysis. Autoimmun Rev. 2012;12:121-126.

3. Wolverton SE. “Chapter 12: Systemic corticosteroids.” Comprehensive Dermatologic Drug Therapy. Philadelphia, Pa.: Saunders; 2012.