The Johns Hopkins Laboratory For Translational Research in Pemphigus TYPES OF PEMPHIGUS Pemphigus Vulgaris Pemphigus is a term used to describe blistering of the skin caused by binding of antibodies to the surface of the cells of the outer layer of the skin, the epidermis. In pemphigus vulgaris, the most common form of pemphigus, there are IgG antibodies that bind to the cell surfaces of epidermis of the skin as well as the epithelium lining mucosal surfaces such as the mouth. As a result, patients develop severe oral ulcerations, and may also have inflammation or erosions of the lining of the eye and eyelids (conjunctiva), the nasal mucosa, or the genital mucosa. Half of the patients also develop blisters or erosions of the skin, often in the head and neck area. Diagnosis is made by biopsying the skin or oral mucosa. The biopsy specimens show deposition of antibodies on the cell surfaces of the epidermis or epithelium by using specialized immunofluorescence techniques performed in our Dermatoimmunology Laboratory. Our laboratory also uses immunofluorescence techniques to detect antibodies in the blood. The titer of these antibodies may be helpful in evaluating the severity of the disease as well as disease course and response to therapy. Without treatment, the mortality of pemphigus vulgaris approaches 100%. The current mortality rate still ranges from 5 to 25 %. However, this still high mortality rate is due to the use of unjustified massive doses of prednisone ( more than 80 mg/kg/day) Therefore, the use of tapered doses of prednisone ( 1m/kg/per day-maximum 80 mg/day) alone or in conjunction with early use of other immunosuppressive agents such as azathioprine (Imuran), mycophenolate mofetil (Cell Cept), or cyclophosphamide (Cytoxan) is a logical and safer approach. In severe cases, a patient may be admitted and undergo plasmapheresis, in which the patient’s serum is removed and replaced with serum that does not contain the causative antibodies is performed. It may take several months for the oral ulcers and blisters of pemphigus vulgaris to disappear after treatment has started, as circulating antibodies remain in the blood for weeks to months. Pemphigus Foliaceus Pemphigus is a term used to describe blistering of the skin caused by binding of antibodies to the surface of the cells of the outer layer of the skin, the epidermis. In pemphigus foliaceus there are IgG antibodies that bind to the cell surfaces of epidermis of the skin. As a result, patients develop superficial cutaneous erosions. Diagnosis is made by biopsying the skin. The biopsy specimens show deposition of antibodies on the cell surfaces of the epidermis or epithelium by using specialized immunofluorescence techniques performed in our Dermatoimmunology Laboratory. Our laboratory also uses immunofluorescence techniques to detect antibodies in the blood. The titer of these antibodies may be helpful in evaluating the severity of the disease as well as disease course and response to therapy. Aggressive immunosuppressive therapies are indicated to control the disease. Long-term immunosuppression using tapered doses of prednisone (a corticosteroid) provides the foundation of treatment for pemphigus vulgaris. And less freqeuntly dapsone (an anyi-inflammatory medication) for mild cases. Many patients will need additional immunosuppression with drugs such as azathioprine (Imuran), mycophenolate mofetil (Cell Cept), or cyclophosphamide (Cytoxan). It may take several months for the erosions and blisters of pemphigus vulgaris to disappear after treatment has started, as circulating antibodies remain in the blood for weeks to months Paraneoplastic Pemphigus Pemphigus is a term used to describe blistering of the skin caused by binding of antibodies to the surface of the cells of the outer layer of the skin, the epidermis. Paraneoplastic pemphigus is a recently-described autoimmune blistering disease that occurs in patients with certain types of cancers. This disease was discovered in 1990 by Dr. Grant Anhalt, the Acting Chairman of the Johns Hopkins University Department of Dermatology, and director of the Johns Hopkins Dermatoimmunology Laboratory. This disorder, which is very rare, is characterized by severe ulceration of the mouth and lips, ulceration and scarring of the lining of the eye and eyelids (conjunctiva), and skin lesions that may include blisters or violaceous plaques. As the antibodies also bind the airways, patients may develop a variety of signs of respiratory disease, which is usually rapidly fatal. Almost all patients have an underlying cancer, which includes non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, Castleman’s disease, thymoma, Waldenstrom’s macroglobulinemia, and sarcomas. The diagnosis is made by biopsying the skin and taking blood samples. The biopsy specimens show deposition of antibodies on the cell surfaces of the epidermis or epithelium by using specialized immunofluorescence techniques performed in our Dermatoimmunology Laboratory. Our laboratory also uses immunofluorescence techniques to detect antibodies in the blood. Our Dermatoimmunology laboratory was the first and remains one of the only laboratories worldwide that performs the gold standard test for confirming that a patient has paraneoplastic pemphigus. This test is called "immunoprecipitation", which looks for antibodies in the blood that bind to particular proteins. Aggressive immunosuppressive therapies are indicated to control the disease. Long-term immunosuppression using tapered doses of prednisone (a corticosteroid) in addition to cyclosporine A (Neoral) provides the foundation of treatment for paraneoplastic pemphigus. If the cancer is a solid tumor that can be surgically removed, patients may show dramatic improvement. Otherwise, most patients die within a year of diagnosis. The major causes of death include respiratory failure and life-threatening infections. IgA Pemphigus Pemphigus is a term used to describe blistering of the skin caused by binding of antibodies to the surface of the cells of the outer layer of the skin, the epidermis. IgA pemphigus is a recently-described rare autoimmune blistering disorder in which IgA antibodies bind to the cell surface of epidermal cells. This disease is different from other types of pemphigus in that the type of antibodies are IgA instead of IgG. The disease may be similar to pemphigus foliaceus with erosions and some blisters or it may be characterized by numerous small pustules. Diagnosis is made by biopsying the skin. The biopsy specimens show deposition of IgA antibodies on the cell surfaces of the epidermis or epithelium by using specialized immunofluorescence techniques performed in our Dermatoimmunology Laboratory. Our laboratory also uses immunofluorescence techniques to detect antibodies in the blood. This is the most benign form of pemphigus, and is usually easily controlled using dapsone, a drug that was initially used in the treatment of leprosy, but which has been found to be very helpful as an anti-inflammatory agent. Some patients may respond to prednisone (a corticosteroids) or retinoids, which are drugs that are used in the treatment of a variety of skin disorders such as acne (Accutane is a retinoid).