Paraneoplastic pemphigus (PNP) is an autoimmune life-threating disorder associated with the tumor, usually limphoproliferative neoplasms.
Pemphigus is a chronic autoimmune disorder that affects the skin and mucous membranes and causes the formation of blisters. The word “paraneoplastic” regards to the association of the disorder to a neoplasm due to an altered immune system. An alternative term for PNP is paraneoplastic autoimmune multiorgan syndrome (PAMS), it reflects the inclusion of the nonbullous cutaneous eruptions and pulmonary involvement that may develop later.
PNP is caused by the presence of tumor in the body, although it’s impossible to predict whether a person will develop PNP or not. In Chinese patients the association between paraneoplastic pemphigus and HLA class II DRB I*03 and HLA-Cw*14 has been reported.
The neoplasm causes the formation and circulation of the tissue-bound antibodies against antigens present in the plakin family. The plakins are involved in the intracellular attachment structures in the skin/respiratory tract/membranes – they keep the skin tissue together throughout the body. Target antigens have been found to include desmoglein-3, desmoglein-1, envoplakin, periplakin, desmoplakin 1, desmoplakin 2, and bullous pemphigoid antigen I.
There are several theories that the tumor can generate plakin protein and this way induces an autoimmune response by creating the so-called cross-reactivity of tumor and epidermal antigens.
As long as the paraneoplastic pemphigus occurs among those who suffer from neoplastic formations – benign and malignant tumors are at risk of developing the pemphigus. The most commonly PNP appears in those who have Castleman’s tumor, non-Hodgkin’s lymphoma, thymoma, follicular dendritic cell sarcoma and chronic lymphocytic leukemia.
[See also: Rathke pouch tumor]
On the skin and mucous membranes occur blisters and painful erosions. The lesions associated with PNP may have 5 forms of clinical presentation:
– “Pemphigus-like”: Discrete blisters, crusts over the raw exuding skin lesions;
– “Pemphigoid-like”: Tense blister(s) on brick red erythema. Typically affect the limbs;
– “Erythema multiforme-like”: Severe lesions;
– “Graft-vs.-host disease-like”: Widespread lichenoid eruption;
– “Lichen planus-like”: Small red flat-topped scaly papules. More common for children;
Usually the first symptoms are lesions of the mucosa of the mouth, the conjunctiva of the eye, anogenital region and esophagus may also be affected. Later appear lesions of the skin. The blisters tent to affect the upper trunk, head, neck and extremities. The erythema can be macular, urticarial, or targetoid, and it may be polymorphous. Lesions may be of the different types at same time or transform gradually.
In some cases occurs the pulmonary insufficiency due to the disturbance of the mucosa of the respiratory tract. The patients develop dyspnea and obstructive lung disease (bronchiolitis obliterans).
The involvement of the eyes ranges from mild conjunctivitis to symblepharon (adhesion of the palpebral conjunctiva of the eyelid to the bulbar conjunctiva of the eyeball) with corneal scarring.
The diagnosis of PNP requires further testing to verify the tumor. Skin biopsy samples show suprabasal acantholysis and interface dermatitis.
The direct immmunofluorescence testing is used to detest Immunoglobulin G, A, or M in other locations except the e[idermis such as intercellular and areas below the epidermis (subepidermal), as well as along the dermoepidermal junction (area that joins the epidermis and dermis).
Usually the diagnosis is fatal. The early diagnosis, detection and the removal of the tumor along with the intravenous injection of immunoglobulins (Gammagard, Gamimune, Sandoglobulin) are the only effective treatment of PNP.
The wounds need to be administrated carefully. They are typically treated with warm compresses, non-adherent (non-stick) dressing, and topical antibiotic ointment. To decrease blistering the immunosuppressive agents such as prednisone, azathioprine, ciclosporin and cyclophosphamide were proposed.
The alteration of the skin barrier puts the patient at risk of developing the local and generalized infection and fastens the fatal outcome of the disease. About 90% of the patient who develop the PNP associated with the malignant tumor die.