Pemphigus

Pemphigus is a rare group of autoimmune diseases that affect the skin and mucous membranes. It is a blistering disease in which autoantibodies are directed against Desmosglein - a protein, which acts like a glue to cement epidermal cells together.

When Desmogleins are targeted, the epidermal cells become detached from one another (acantholysis) and this produces blisters or lesions that fail to heal. These blisters can then progress to become sores that cover a significant area of the skin and the mouth.

Till the 1960s little was known about pemphigus.It was in 1971 that the autoimmune nature of this disease was published.

Pemphigus has a world wide occurrence and affects both males and females, of all ethnic groups.





Some people have a greater pre- ponderence to develop the disease such as those with a familial history and those with other auto- immune diseases such as Myasthenia gravis or thyroid cancer.

Drug-induced pemphigus vulgaris : Drugs reported most significantly in association with pemphigus vulgaris include penicillamine, captopril, cephalosporin, pyrazolones, nonsteroidal anti-inflammatory drugs (NSAIDs), and other thiol-containing compounds. Rifampin, emotional stress, thermal burns, ultraviolet rays, and infections (eg, coxsackievirus, Herpesviridae family) have also been reported as triggers for pemphigus vulgaris.




Clinical Presentation:

Mucous membranes typically are affected first in pemphigus vulgaris. Mucosal lesions may precede cutaneous lesions by weeks or months. Patients with mucosal lesions may present to dentists, oral surgeons, or gynecologists.

• Mucous membranes

  • Intact bullae are rare in the mouth. More commonly, patients have ill-defined, irregularly shaped, gingival, buccal, or palatine erosions, which are painful and slow to heal. The erosions extend peripherally with shedding of the epithelium.
  • The mucous membranes most often affected in pemphigus vulgaris are those of the oral cavity, which is involved in almost all patients with pemphigus vulgaris and sometimes is the only area involved. Erosions may be seen on any part of the oral cavity. Erosions can be scattered and often are extensive. Erosions may spread to involve the larynx, with subsequent hoarseness. The patient often is unable to eat or drink adequately because the erosions are so uncomfortable.
  • In juvenile pemphigus vulgaris, stomatitis is the presenting complaint in more than 50% of the cases.
  • Other mucosal surfaces may be involved, including the conjunctiva,esophagus (causes odynophagia and/or dysphagia),labia, vagina, cervix, vulva, penis, urethra, nasal mucosa, and anus.
• Skin

  • The primary lesion of pemphigus vulgaris is a flaccid blister filled with clear fluid that arises on healthy skin or on an erythematous base, as shown in the images below.Early, small blister filled with clear fluid arises on healthy skin.Flaccid blister filled with clear fluid arises on healthy skin.
  • The blisters are fragile; therefore, intact blisters may be sparse. The contents soon become turbid, or the blisters rupture, producing painful erosions, which is the most common skin presentation and is shown in the image below. Erosions often are large because of their tendency to extend peripherally with the shedding of the epithelium.An erosion.
• Vegetating pemphigus vulgaris: Ordinary pemphigus vulgaris erosions may develop vegetation. Lesions in skin folds readily form vegetating granulations. In some patients, erosions tend to develop excessive granulation tissue and crusting, and these patients display more vegetating lesions. This type of lesion tends to occur more frequently in intertriginous areas and on the scalp or face. The vegetating type of response can be more resistant to therapy and can remain in one place for long periods.
• Pemphigus in pregnancy: Pemphigus vulgaris occurring in pregnancy is rare. When present, maternal autoantibodies may cross the placenta, resulting in neonatal pemphigus. Neonatal pemphigus is transient and improves with clearance of maternal autoantibodies.Treatment of pemphigus vulgaris in pregnancy is with oral corticosteroids; however, prednisone and its metabolites cross the placenta and have been associated with low birth weight, prematurity, infection, and adrenal insufficiency.
• Nikolsky sign: In patients with active blistering, firm sliding pressure with a finger separates normal-appearing epidermis, producing an erosion. This sign is not specific for pemphigus vulgaris and is found in other active blistering diseases.
• Asboe-Hansen sign: Lateral pressure on the edge of a blister may spread the blister into clinically unaffected skin.
  
  
  
  
  Histological Findings-Histopathology demonstrates an intradermal blister. The earliest changes consist of intercellular edema with loss of intercellular attachments in the basal layer. Suprabasal epidermal cells separate from the basal cells to form clefts and blisters. Basal cells are separated from one another and stand like a row of tombstones on the floor of the blister, but they remain attached to the basement membrane. Blister cells contain some acantholytic cells. Histopathology can help differentiate pemphigus vulgaris from pemphigus foliaceous, which demonstrates a more superficial epidermal cleavage.
  Tzanck preparation is a smear taken from the base of a blister or an oral erosion that contains acantholytic cells. Blistering is preceded by eosinophilic spongiosis in some patients. The superficial dermis has a mild, superficial, mixed inflammatory infiltrate, which includes some eosinophils.
  
  
  
  

  Medication Summary

  The aim of treatment is to reduce the inflammatory response and autoantibody production. While target-specific therapy is not available, non–target-specific treatments currently are used. The most commonly used medications are corticosteroids.

  The introduction of corticosteroids has reduced mortality greatly, but significant morbidity remains. Immunosuppressants should be considered early in the course of disease, as steroid-sparing agents. Mycophenolate mofetil and azathioprine are the usual agents considered as initial choices.Wound care for erosions includes daily gentle cleaning, application of topical agents to promote wound healing, and use of nonadhesive dressings. The goal of wound care is to promote healing, minimize trauma to the surrounding skin, and diminish scarring.