Paraneoplastic dermatoses are a group of diseases and symptoms of skin lesions that occur under the influence of malignant neoplasms of internal organs. According to their manifestations, dermatoses associated with cancer have much in common with common dermatological diseases: itching, excoriation, erythematous, vesicular-bullous rashes, lichenification, pigmentation. However, they differ in the greater prevalence of lesions and torpid course. Diagnosis includes the identification of characteristic symptoms during general examination and dermatoscopy, histological examination of the skin. It is possible to achieve remission only if the cancerous tumor is completely removed.
In the scientific literature, the term “paraoncological dermatoses” is also used to refer to this group of diseases. The first person who drew attention to the connection of benign dermatoses and oncological disease was the French doctor A. Trusseau in 1865. J. Darrier, nicknamed “the father of modern dermatology” for the first time established the connection of black acanthosis with cancer of the gastrointestinal tract. Paraneoplastic dermatoses develop in 27% of patients with oncological diseases. In a third of cases, skin damage is the first, and sometimes the only sign indicating the development of cancer. Skin symptoms are observed in 75% of cancer patients with advanced forms of cancer.
The development of paraneoplastic dermatoses is determined by a growing cancerous tumor that alters the functioning of the entire body as a whole and the skin in particular. Different types of malignated cells have a whole spectrum of adaptive reactions, which explains the variety of forms of paraneoplastic processes. The main mechanisms of the indirect effect of the tumor on the condition and functioning of the skin as an organ include:
- Secretion of biologically active substances. Cancer cells synthesize and secrete into the blood an increased amount of growth factors, cytokines, prostaglandins, immunoglobulins, enzymes, embryonic proteins that change the speed and nature of metabolic processes.
- Disruption of the immune system. Immunosuppression is one of the leading mechanisms for the preservation of malignant neoplasms in the body, since the immune system normally recognizes degenerated cells and destroys them. In second place in importance is the formation of immune complexes that interact with the tissues of the dermis and cause a pronounced inflammatory reaction.
- Violation of the transmission of regulatory signals. The change in the physiological response of the cell to the stimulating effect occurs as a result of the formation of ectopic receptors of the cell membrane, blocking of normal receptors by biologically inactive analogues of hormones that are synthesized by the tumor.
- Release of bioactive proteins and peptides. In conditions of pathological vascularization of the tumor node, with massive destruction of cells, a large number of enzymes and other protein molecules are released, the presence of which in the blood and tissue fluid is not characteristic. They change metabolic processes, provoke the development of inflammation, tissue necrosis and other pathological reactions.
The importance in the development of paraoncological dermatosis is not the direct effect of the tumor on the tissues, but its indirect effect on the metabolic, immune and biochemical reactions occurring in the body. In the process of cancer transformation, normal cells lose their specialized functions and structure, begin to synthesize and release biologically active substances into the blood that ensure vascular growth, blood supply and nutrition of the cancer node. The consequence of these disorders is the appearance of a variety of clinical symptoms: itching, rash, necrosis, inflammation, etc.
Immune shifts can occur at the stage of transformation of normal cells into cancer cells, that is, long before the formation of a tumor, which can be detected using instrumental and laboratory diagnostic methods. At this stage, the cells lose their ability to differentiate, synthesize a completely unusual range of products. The development of the paraneoplastic process during this period is due to the recognition by the immune system of transformed cells as foreign. Immune and autoimmune complexes can damage normal cells simultaneously with cancer.
There is currently no single generally accepted classification of paraneoplastic dermatoses in clinical dermatology. Most researchers agree that it is advisable to divide all skin lesions into groups depending on the frequency of their detection in malignant diseases of internal organs. According to this classification , all paraoncological dermatoses are divided into:
- Obligate. The appearance of paraneoplastic skin symptoms is usually caused by cancer of the internal organs. According to the clinical picture of dermatosis, it is often possible to judge the localization of the tumor node and the nature of the course of the oncological process. This group includes the malignant form of black acanthosis, Gammel’s circular erythema, Basex acrokeratosis, and so on.
- Optional. The association of benign skin manifestations and visceral cancer is statistically significant, however, the probability of simultaneous occurrence of these processes is lower than for the group of obligate paraneoplastic dermatoses. These include carcinoid syndrome, reticulogistiocytoma, acquired pachydermoperiostosis and keratodermia of the palms and soles, bullous pemphigoid, etc.
- Probable. Dermatoses from this group can be associated with malignant neoplasms with a progressive course of dermatological disease, resistance to therapy, and frequent recurrence. The group of probable paraneoplastic dermatoses includes primary systemic amyloidosis, exfoliative erythroderma, late cutaneous porphyria and some others.
Facultative paraneoplastic dermatoses are detected in 54% of cases, probable in 32%. Obligate paraneoplasias account for 14%. In 85% of cases, obligate paraneoplastic skin changes are detected in advanced forms of cancer.
A number of clinicians in their work use the classification of paraneoplastic dermatoses, which takes into account the morphological features of skin lesions. According to this principle, all paraoncological dermatological changes in patients with extracutaneous tumors can be divided into three groups:
- Erythematous. These include Gammel’s circular creeping erythema, Darya’s centrifugal erythema, multiform exudative erythema, which are grouped based on the prevailing symptom – intense limited redness of the skin. According to statistics, paraneoplastic erythematous dermatoses develop more often in women.
- Pruriginous. The leading symptom of paraneoplastic pruriginous dermatoses is intense persistent itching of the skin. Its occurrence is associated with an autoimmune reaction, which is caused by cytolysis of tissues. These include chronic recurrent urticaria, chronic adult pruritus and nodular prurigo.
- Vesiculobullous. A distinctive feature of vesiculobullous dermatoses is the formation of blisters of different sizes. This group includes seborrheic and vulgar pemphigus, bullous pemphigoid, During’s herpetiform dermatitis.
The external manifestations of skin lesions resemble known dermatoses. It is possible to suspect the connection of the revealed skin pathology with the latent oncological process in cases when dermatosis develops in an older or elderly patient, is characterized by significant prevalence and resistance to therapy. So, for example, with During’s herpetiform dermatitis, itching, eczematous and erythematous rashes do not respond to specific therapy. Often dermatosis associated with visceral cancer occurs with an increase in common symptoms, such as weakness, fatigue, weight loss.
The first signs of paraneoplastic skin disease appear simultaneously or almost simultaneously with a cancerous tumor. At the same time, the period between the onset of dermatosis and the detection of cancer can range from several months to several years. The maximum degree of cancer risk (80%) exists in the first three years after the initial manifestation of nonspecific skin changes. Against the background of successful surgical treatment, chemo- or radiation therapy, a rapid regression of paraneoplastic skin manifestations is observed. With the recurrence of cancer and metastasis, dermatosis resumes its course.
The exceptions are malignant neoplasms caused by hereditary syndromes (neurofibromatosis, Cowden’s disease, Gardner, Muir-Torre, Pates-Jaegers syndromes). In these cases, there is no parallelism between the course of cancer and dermatosis, which is due to the mutual genetic determinism of tumor and non-tumor elements.
Skin damage on the background of immunosuppression creates favorable conditions for the unhindered penetration of bacteria and fungi into the tissues, activation of dormant infection in the body. For example, the incidence of shingles, which is caused by the herpes simplex virus, is significantly higher in patients with solid malignant tumors compared to healthy individuals and patients suffering from non-oncological diseases.
The inflammatory process that develops when an infection is attached significantly aggravates the patient’s condition and complicates treatment. Violation of the general condition leads to a decrease in working capacity. Skin itching dramatically reduces the quality of life of patients, which exhausts the patient, makes sleep shallow, makes it difficult to fall asleep.
A comprehensive examination of a patient with suspected paraneoplastic dermatosis pursues two main goals: the first is to make an accurate dermatological diagnosis, the second is an oncopoisk. The list of studies in each case is determined by the clinical picture and the place of the intended localization of the primary cancer node. A comprehensive examination of the patient may include:
- General inspection. To determine the type of dermatosis in most cases, it is possible according to the general examination with dermatoscopy. Dermatoses in neoplasia must be differentiated from metastatic lesions of the dermis and the germination of its tumor, complications of therapy, the consequences of nutritional deficiency. In women, at the reception of a dermatologist, palpation of the mammary glands is performed if cancer of this localization is suspected.
- Blood test. Routine studies (general and biochemical blood tests) are performed, studies are conducted using immune and biochemical methods in order to identify substances synthesized by the tumor. Quantitative indicators of studies allow us to judge the stage of the oncological process and the degree of differentiation of the tumor.
- Visualization of the tumor. Medical imaging methods allow to establish the localization of the cancer node, its size, and the stage of the oncological process: Soft tissue ultrasound, computed tomography and magnetic resonance imaging. Examination of hollow organs is carried out using endoscopy.
- Histological examination. Skin samples are obtained during a biopsy. Microscopic examination of a biopsy in the case of paraneoplastic dermatosis is carried out in order to make the correct diagnosis of a dermatological disease and determine the type of tumor.
It is possible to eliminate skin manifestations only if the underlying malignant neoplasm is cured. However, dermatological symptoms may appear long before the detection of cancer of internal organs. The patient may need symptomatic therapy for a long time, which includes:
- General treatment. Antihistamines, anti-inflammatory drugs, antibiotics, antimycotics in the form of tablets, intramuscular and intravenous injections are prescribed. Treatment is carried out until the skin manifestations of dermatosis disappear and remission occurs. During therapy, a dermatologist can change medications to more effective ones if there is no improvement.
- Local treatment. It plays an auxiliary role in general therapy. It involves local application to the skin and mucous membranes of solutions, creams and ointments with antiseptic, analgesic, antipruritic, drying effect. Promotes rapid relief of symptoms, prevents infection.
Prognosis and prevention
Cases of dermatosis development in older and elderly people require special attention. In this category of patients, the risk of cancer compared to young people increases many times. The presence of a paraneoplastic skin lesion requires a comprehensive examination to detect cancer. Timely diagnosis and elimination of cancer can prolong the patient’s life for several years. Methods for the prevention of paraoncological dermatoses have not been developed. A healthy lifestyle, rejection of bad habits, elimination of harmful industrial and environmental factors (work with asbestos, etc.) allows to reduce the likelihood of developing oncology.