Pemphigus vulgaris

Etiopatogenesis Pemphigus is an autoimmune disorder. The immune system produces antibodies against specific proteins in the skin and mucus membranes. These antibodies break the bonds between skin cells. This leads to the formation of a blister. A drug called penicillamine, which removes certain materials from the blood (chelating agent) Blood pressure medications called ACE inhibitors

 Blisters in pemphigus vulgaris are associated with the binding of IgG autoantibodies to keratinocyte cell surface molecules. These intercellular or pemphigus vulgaris antibodies bind to keratinocyte desmosomes and to desmosome-free areas of the keratinocyte cell membrane. The binding of autoantibodies results in a loss of cell-to-cell adhesion, a process termed acantholysis. The antibody alone is capable of causing blistering without complement or inflammatory cells.

Symptoms About 50% of people with this condition first develop painful blisters and sores in the mouth, followed by skin blisters. Skin sores may come and go. The skin sores may be described as: Draining Oozing Crusting Peeling or easily detached

Exams and tests The skin separates easily when the surface of unaffected skin is rubbed sideways with a cotton swab or finger. This is called a positive Nikolsky's sign. A skin biopsy is usually done to confirm the diagnosis. Treatment Severe cases of pemphigus may need wound management, similar to the treatment for severe burns. People with this condition may need to stay in a hospital and receive care in a burn unit or intensive care unit. Treatment is aimed at reducing symptoms, including pain. It also aims to prevent complications, especially infections.

Treatment may involve: Antibiotics and antifungal medications to control or prevent infections Fluids and electrolytes given through a vein (IV) IV feedings if there are severe mouth ulcers Numbing (anesthetic) mouth lozenges to reduce mouth ulcer pain Pain medications if local pain relief is not enough Body-wide (systemic) therapy is needed to control pemphigus and should be started as early as possible. Systemic treatment includes: An anti-inflammatory drug called dapsone,Corticosteroids Medications containing gold Medications that suppress the immune system (such as azathioprine, methotrexate, cyclosporin, cyclophosphamide, mycophenolate mofetil, or rituximab)

Toxic Epidermal Necrolysis (TEN)

TEN
A.k.a Lyells syndrome. A life-threatening mucocutaneous disease characterized by widespread erythema, necrosis, and bullous detachment of the epidermis and mucous membranes, resulting in exfoliation and possible sepsis or death.

Etiology of TEN
Adverse reactions to drugs Vaccinations Malignant disorders Graft versus host disease (GVHD) Infections Medications

TEN is idiosyncratic, and its occurrence is not easily predicted.

Pathogenesis of TEN
TEN is believed to be an immune-related cytotoxic reaction aimed at destroying keratinocytes that express a foreign antigen. The widespread epidermolysis and blistering of TEN results from keratinocyte apoptosis an organized series of biochemical reactions leading to cell changes and cell death.

 The number of inflammatory T cells in the skin of patients with TEN is variable and perhaps too low to explain the widespread destruction. There is evidence supporting several immunopathologic pathways leading to keratinocyte apoptosis in TEN:

1. Fas ligand activation on keratinocyte membranes leading to death receptormediated apoptosis. 2. Release of destructive proteins from cytotoxic T lymphocytes
3. Overproduction of T cell and/or macrophagederived cytokines, tumor necrosis factor- 4. Drug-induced secretion of granulysin from CTLs, natural killer cells, and natural killer T cells

Clinical Manifestation Toxic Epidermal Necrolysis

Typical symptoms are as follows: Cough productive of a thick purulent sputum Headache Malaise Conjunctivitis

The rash can begin as macules (on the face, neck, upper trunk)

develop into papules, vesicles, bullae, urticarial plaques, or confluent erythema.

Distribution
Stevens-Johnson syndrome
<10% body surface area (BSA) detachment

Overlapping Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN)

Detachment of 10-30% BSA

Toxic epidermal necrolysis

Detachment of >30% BSA

Severe cases of TEN

large sheets of epithelium slide off the entire body at pressure points (Nikolsky's sign), exposing weepy, painful, and erythematous skin Painful oral crusts and erosions, keratoconjunctivitis, and genital problems accompany skin sloughing in up to 90% of cases Bronchial epithelium may also slough, causing cough, dyspnea, pneumonia, pulmonary edema, and hypoxemia.

Figure: Patient with Toxic Epidermal Necrolysis

Treatment of Toxic Epidermal Necrolysis

Support ABCs Discontinue offending agents Maintaining fluid and electrolyte homeostasis Manage oral lesions with mouthwashes. Topical anesthetics are useful in reducing pain and allowing the patient to take in fluids Severe cases, admit to the ICU and consider transfer to a burn center