Paraneoplastic pemphigus (Latin pemphigus paraneoplasticus) is a disease belonging to paraneoplastic dermatological syndromes. The cause of skin lesions in paraneoplastic pemphigus is a cancer that develops in the body. Paraneoplastic pemphigus may be the first symptom of neoplastic disease, therefore the diagnosis of pemphigus-type lesions always requires the exclusion of their paraneoplastic basis. Find out how paraneoplastic pemphigus develops and what types of cancer it can accompany. What is the diagnosis and treatment of paraneoplastic pemphigus?

Paraneoplastic pemphigus(Latinpemphigus paraneoplasticus ) is a special type of pemphigus. Like other paraneoplastic syndromes, paraneoplastic pemphigus is caused by the body's response to the cancer that develops in it.

The immune system tries to defend itself against the disease, but its response may be misplaced - this is how autoantibodies are produced. Paraneoplastic syndromes are often the first sign of the development of a cancer in the body.

Apart from paraneoplastic pemphigus, there are many other variants of this disease that are not related to cancer. According to estimates, paraneoplastic pemphigus accounts for 3-5% of all pemphigus cases. Nevertheless, in the case of diagnosing this disease, one should always think about the possible paraneoplastic basis and exclude the possible coexistence of neoplastic disease.

How is paraneoplastic pemphigus formed?

Pemphigus (Latinpemphigus ) is a group of diseases belonging to the blistering skin diseases. The main symptom of pemphigus is blisters forming in the epidermis, which can spread over large areas of the skin. Blisters are often accompanied by erosions (sometimes very deep), erythematous changes and exfoliation of the epidermis. In some cases, pemphigus also affects the mucous membranes, as well as hair and nails.

Pemphigus belongs to the group of autoimmune diseases. They are caused by improper recognition of the body's own cells by the immune system. By mistaking self antigens as foreign, the immune system tends to destroy its owncells. The result of this reaction is the production of the so-called autoantibodies, i.e. antibodies directed against your tissues.

In pemphigus, these antibodies have a destructive effect on epidermal cells, which is manifested in the formation of blisters. A characteristic feature of pemphigus is the phenomenon of acantholysis. Acantholysis is the breakdown of connections between epidermal cells, which leads to the formation of characteristic skin changes.

What are the causes of autoimmune phenomena in pemphigus? In most cases, the underlying cause of the improper "switch" of the immune system remains unknown. In some patients, the role of genetic factors and viral infections is suspected. Sometimes pemphigus changes appear after taking certain medications or eating specific foods (the so-calledAlliumfoods containing sulfur compounds: leek, garlic, onion).

Paraneoplastic pemphigus - symptoms and course

A characteristic feature of paraneoplastic pemphigus is the extremely frequent involvement of the oral mucosa. The first symptom of the disease in most cases is painful, bleeding and difficult to heal erosions that appear on the inside of the cheeks, on the tongue, palate, lips or gums. Over time, the lesions may spread to nearby mucous membranes and affect the throat and nasal mucosa (also leading to bleeding).

Paraneoplastic pemphigus relatively often causes ophthalmic complications - initially affecting the conjunctiva and then subsequent structures of the eyeball, it can lead to irreversible damage to the organ of vision.

The typical lesions of the mucous membranes are usually accompanied by skin lesions, which can take various forms after some time. Their unambiguous recognition may be difficult at first. In addition to the blisters typical of pemphigus, the skin may develop changes resembling erythema multiforme, lichen planus and other dermatological diseases.

Skin changes in pemphigus are called polymorphic, which means that they occur simultaneously in different forms:

  • blisters
  • blush
  • haemorrhagic changes
  • lumps
  • erosion
  • spots of exfoliation
  • scabs
  • deep ulcers

Practically the entire surface of the skin can be occupied with them, although changes in the upper half of the body are observed slightly more often.

There is another reason why paraneoplastic pemphigus is a special subtype of pemphigus. Antibodies causing paraneoplastic pemphigus exert a destructive effectnot only on the cells of the epidermis and oral mucosa. They are the only ones that can damage other epithelia in our body. For this reason, paraneoplastic pemphigus can also affect other organs with mucous membranes:

  • digestive tract
  • respiratory system
  • genitals

In the scientific literature, more and more paraneoplastic pemphigus is referred to as " Paraneoplastic autoimmune multi-organ syndrome " ( PAMS syndrome ), which emphasizes the multitude of changes and organs affected by this disease.

Complications from other organs, especially from the respiratory system, respond poorly to treatment, significantly worsen the prognosis and pose the greatest risk to patients.

What cancers can accompany paraneoplastic pemphigus?

Although the literature describes various types of neoplasms with paraneoplastic pemphigus coexistence, the vast majority of them are hematological malignant growths. These include various types of lymphomas and leukemias. These include, first of all, B-cell lymphomas, chronic lymphocytic leukemia (CLL) and thymoma.

An example of a benign proliferative disease that can also be associated with paraneoplastic pemphigus is Castleman's tumor.

Squamous cell carcinomas, soft tissue sarcomas and melanomas are much less common neoplasms underlying paraneoplastic pemphigus.

Paraneoplastic pemphigus - diagnosis

The diagnosis of paraneoplastic pemphigus is based on several types of tests. The first step in making the diagnosis is a carefully collected history and physical examination, with particular emphasis on skin and mucosal lesions.

Diagnosis of paraneoplastic pemphigus "by eye" is of course not possible, as the clinical picture may suggest many other dermatological diseases.

The occurrence of difficult to heal blisters and erosions of an unidentified cause is an indication for the collection of specimens, which are then subjected to a histopathological examination. Under the microscope, the phenomenon of acantholysis is usually visible, i.e. the loss of connectivity between epidermal cells typical of pemphigus.

In order to finally establish a diagnosis, it is necessary to detect the underlying autoantibodies in the blood. In the case of paraneoplastic pemphigus, these are the so-called PNP antibodies directed against various antigens of the epidermis (including demoplakin and envoplakin).

Combination of the clinical picture, the test resulthistopathological and determination of specific autoantibodies allows for the diagnosis.

At the diagnostic stage, it is equally important to recognize the neoplasm underlying the paraneoplastic pemphigus. Of course, it is easier to adopt the correct diagnostic path when a patient with a diagnosed cancer develops skin changes typical of pemphigus. Sometimes, however, paraneoplastic pemphigus is diagnosed before cancer is diagnosed. Then it is necessary to significantly extend the diagnosis, especially towards hematological diseases.

Usually, thorough blood tests and additional imaging tests (computed tomography of the chest and abdomen) are performed. It is estimated that in about 1/3 of cases the symptoms of paraneoplastic pemphigus precede the diagnosis of the underlying cancer.

Treatment of paraneoplastic pemphigus

Treatment of paraneoplatic pemphigus requires multidirectional activities. The treatment of the underlying disease, i.e. the neoplasm underlying the pemphigus, gives the best chance of effective therapy. In the case of monofocal tumors, surgery is of the greatest importance, while in the treatment of disseminated hematological neoplasms, various forms of chemotherapy are primarily used. Removal or inhibition of the neoplastic disease reduces the amount of produced antibodies and alleviates the symptoms of pemphigus.

Of course, symptomatic therapy is used simultaneously with oncological treatment. High doses of glucocorticosteroids are the first line of drugs that block the abnormal reaction of the immune system.

In the case of resistance to this group of drugs, more intensive immunosuppressive treatment is implemented, whose task is to suppress the immune response. The most commonly used immunosuppressants include azathioprine, cyclosporine, and mycophenolate mofetil.

Unfortunately, in many cases of paraneoplastic pemphigus, such pharmacotherapy remains ineffective.

More aggressive methods of therapy include, for example, plasmapheresis, i.e. the purification of plasma from autoantibodies that cause disease symptoms. Despite intensive treatment, paraneoplastic pemphigus can be resistant to all forms of therapy.

It is particularly difficult to subside any changes in the mucous membranes, while the involvement of the gastrointestinal tract and the respiratory tract is practically irreversible and is associated with a very serious prognosis.

About the authorKrzysztof BialaziteA medical student at Collegium Medicum in Krakow, slowly entering the world of constant challenges of the doctor's work.She is particularly interested in gynecology and obstetrics, paediatrics and lifestyle medicine. A lover of foreign languages, travel and mountain hiking.

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Dermatology