In collaboration with the European Dermatology Forum (EDF) and the European Academy of Dermatology and Venereology (EADV
Chronic pruritus (CP) is a common symptom in medical practice and occurs in many dermatological and systemic diseases. Its significant frequency causes a significant burden on health authorities and negatively affects the quality of life of patients. This guide focuses on the symptoms of itching, not the disease. Since this symptom can be caused by many diseases, there is no single approach to its treatment. Each of the forms of itching should be considered separately.
Today, there is a significant lack of appropriate randomized controlled trials (RCTs), due to the variability and complexity of the symptom, the multifactorial nature of the etiology of pruritus, and the lack of clearly defined criteria for the effectiveness of treatment.
The matter is further complicated by the fact that the results of RCTs for some types of pruritus are inconsistent. However, new therapies have been proposed to improve care for these patients. In addition, a large number of expert recommendations are generated.
The state of health systems in many countries and their socio-economic situation with a constant reduction in funding cause an increase in the need for appropriate recommendations. These recommendations are based on the consensus of participating countries, but also include country-specific treatments and healthcare settings.
Moreover, it should be taken into account that some methods of local and systemic therapy are prescribed for unregistered indications, which require the informed consent of the patient. If such methods cannot be carried out by the therapist, cooperation with specialized pruritus centers is useful. This guidance applies to all areas of medicine in which clinicians deal with patients with chronic disease. This also applies to patients with chronic scratching in prurigo nodosum and lichen simplex. The guide focuses on more than just dermatology.
Definition and clinical classification of chronic pruritus
The definitions given in this guide have been agreed upon by the European contributors, however some of them have caused some controversy. Most researchers agree that the terms «pruritus» and "itch", which are used in English literature to refer to itching, are equivalent. It is advisable to isolate acute and chronic (6 weeks or more) of its forms.
Itching - a sensation that makes you want to itch. According to The International Forum on the Study of Itch (IFSI), chronic pruritus is defined as pruritus lasting 6 weeks or more. According to the IFSI, the term "itch without matter" (pruritus sine materia) is not used in these guidelines. If patients do not have a disease that caused itching, the term “itch of unknown origin” or “itch of unknown origin” is used. (ZNG).
The terms "itching of unknown etiology" should be avoided, since in most clinically established forms of pruritus, the mechanism of its occurrence remains unknown (for example, pruritus associated with chronic kidney disease (CKD). These guidelines apply to patients with chronic kidney disease of various, including unknown, genesis. pruritus has been established, refer to appropriate specific guidelines (eg, pruritus associated with atopic dermatitis (AD), cholestatic pruritus).
According to the IFSI classification, the etiology of chronic disease can be :
- I - dermatological;
- II - system;
- III - neurological;
- IV - somatoform;
- V - mixed etiology;
- VI - other.
The IFSI classification takes into account clinical differences in pruritic patients with primary skin lesions/inflammation, normal skin, and chronic secondary skin lesions due to scratching. Somatoform pruritus – it is an itch in which mental and psychosomatic factors play a decisive role in its initiation, determine the intensity of the itch, as well as its increase and persistence. For the diagnosis of this form, it is better to use positive and negative diagnostic criteria.
Epidemiology of chronic pruritus and incidence
Data on the prevalence of chronic disease are extremely limited. It obviously increases with age, but the number of relevant epidemiological studies is insufficient. It is estimated that about 60% of older patients (≥65 years) suffer weekly from intermittent moderate to severe itching, called geriatric pruritus, or pruritus of the elderly.
In a population-based, cross-sectional study of 1900 adults, 8-9% of the general population developed acute pruritus, which was the leading symptom in all age groups. Furthermore, itching has been found to be closely associated with chronic pain.
Recent studies have shown that the incidence of chronic disease at any given time is 13.5% in the general adult population and 16.8% in cancer screeners. The incidence of chronic disease over a 12-month period was 16.4%, and its prevalence during the lifetime, according to a population-based cross-sectional study conducted in Germany, was 22%. Based on these data, it can be assumed that the prevalence of chronic disease in the general population is higher than previously reported.
CS can be caused by both dermatological and systemic diseases. However, in 8-15% of patients, the underlying cause of pruritus remains unknown. The frequency of itching in patients with primary rashes depends on the skin disease that caused it. For example, pruritus occurs in all patients with AD and urticaria, and in approximately 80% of patients with psoriasis. Systemic diseases such as primary biliary cirrhosis (PBC) and CKD are associated with pruritus in 80-100% and 40-70% of cases, respectively. In patients with Hodgkin's lymphoma, itching is also a common symptom and occurs in more than 30% of patients.
Only a small number of studies have focused on the incidence of chronic disease in primary care. According to the Australian BEACH program and the Longitudinal National Study of Therapeutic Activity, 0.6% of patients who presented for help complained of pruritus, excluding perianal, periorbital and otic pruritus.
In Britain in 1991-1992. The fourth National Study on Therapeutic Pathology Incidence was conducted with 502,493 patients (1% of the population of England and Wales). It was shown that the risk is 468042 patient-years, pruritus and related diseases were detected in 1.04% of consultations (0.73% in men; 1.33% in women). On about. In Crete, where patients with skin pathology receive predominantly inpatient rather than primary care, pruritus was diagnosed in 6.3% of 3715 patients.
Clinical picture of chronic itching in various diseases
I. Itching in pathological conditions
Itching of the skin with and without inflammation
CS can often be observed in patients with dermatoses with primary skin lesions and systemic diseases without initial skin lesions. In systemic diseases, the skin may remain intact or be damaged by scratching or rubbing. In this case, the diagnosis may be difficult. Systemic diseases associated with pruritus are listed in panel 1.
Panel 1. Systemic diseases that may be accompanied by itching
Metabolic and endocrine diseases:
- chronic renal failure;
- liver disease with or without cholestasis;
- hyperparathyroidism;
- hyper- or hypothyroidism;
- iron deficiency.
Infectious diseases:
- HIV / AIDS;
- parasitosis, including helminthiases.
- Hematological disorders:
- polycythemia vera,
- myelodysplastic syndrome;
- lymphoma, including Hodgkin's lymphoma.
Neurological diseases:
- multiple sclerosis;
- brain tumors;
- paresthesia in the back;
- brachioradial pruritus;
- postherpetic neuralgia.
Psychiatric or psychosomatic illness:
- depression
- affective disorders;
- hallucinations;
- obsessive and compulsive disorders;
- schizophrenia;
- power failure.
In some cases, itching may precede the diagnosis of the underlying disease by several years. In recent years, some mechanisms of pruritus on inflamed and unaltered skin have been elucidated (see the original version of the EDF guidelines, www.euroderm.org).
The following sections present some of the most common patient populations as well as systemic diseases associated with chronic disease.
Chronic itching in kidney disease
The pathophysiology of CKD-associated pruritus is still unknown. The mechanisms that cause it include direct metabolic factors, among which likely candidates are an increase in the concentration of divalent ions (calcium, magnesium), parathyroid hormone (PTH), histamine and tryptase, dysfunction of peripheral and central nerves, the involvement of opioid receptors (μ- and &kappa ;- receptors), as well as skin xerosis (dryness). New evidence suggests a possible role for microinflammation, which is quite common in uremia.
Chronic pruritus in liver disease
Itching is a common symptom in patients with cholestasis (due to mechanical obstruction), metabolic disorders or inflammatory diseases. It can be quite pronounced, and in some cases it can precede the diagnosis, such as PBC, by several years. In patients with infectious diseases of the liver (hepatitis B, C) or toxic damage to it (for example, alcohol), itching is less common. Hepatic pruritus is often generalized, characterized by involvement of the palms and soles.
According to one hypothesis, the occurrence of itching in liver diseases is due to an increase in the tone of opioid receptors, which affects the transmission of nerve impulses. The success of the [mu]-opioid receptor antagonists (nalmefene) supports this hypothesis.
It has recently been shown that elevated serum levels of autotoxin (an enzyme that converts lysophosphatidylcholine to lysophosphatidyl acid) leads to an increase in lysophosphatidyl acid concentration, which is specific for cholestatic pruritus, but not for other forms of systemic pruritus. Rifampicin significantly reduces pruritus intensity as well as autotoxin activity in pruritic patients. The additional antipruritic effect of rifampicin may in part be explained by suppression of pregnane X receptor (PXR-) dependent transcriptional expression of the autotoxin.
Itching due to endocrine and metabolic diseases
Among patients with hyperthyroidism and diabetes mellitus, itching occurs in less than 10%. With hypothyroidism, itching is more likely due to dry skin. Patients with primary hyperparathyroidism often complain of itching. The pathophysiology of pruritus in primary hyperparathyroidism is still unknown. These patients are often deficient in vitamin D and minerals (zinc, etc.), which may lead to chronic disease. Iron deficiency is often associated with pruritus, the mechanism of which is unknown. Excess iron (with hemochromatosis) can cause chronic disease.
Chronic pruritus in malignant neoplasms
Some malignant neoplasms, including tumors, bone marrow diseases, lymphoproliferative disorders, may be accompanied by itching. In addition to the toxic products produced by the tumor itself, the mechanism of pruritus is based on allergic reactions to the compounds that are released, as well as direct damage to the brain or nerves (in brain tumors). With polycythemia vera, more than 50% of patients complain of itching.
Aquagenic itching, accompanied by a feeling of tightness of the skin and occurring after contact with water, is a characteristic, but not an obligatory symptom. It is believed that itching is caused by high levels of histamine, which is released by an increased number of basophilic granulocytes. This is especially pronounced in patients with polycythemia vera who have a JAK2 617V mutation.
Itching in Hodgkin's lymphoma often begins in the lower extremities and is most pronounced at night, then quickly becomes generalized. Several factors, such as the secretion of leukopeptidases and bradykinin, the release of histamine, and elevated levels of IgE accumulated in the skin, may contribute to the pruritus of lymphoma. Patients with carcinoid syndrome may experience itching, flushing, diarrhea, and cardiac symptoms.
Itching due to infectious diseases
Some generalized infectious diseases are accompanied by itching. Moreover, pruritic papular rashes or eosinophilic folliculitis may develop in HIV-infected patients. This pathology is easily detected during examination and histological examination of the skin and has a high positive predictive value. Whether toxocariasis infection results in pruritus in a significant number of patients must be established.
Itching in neurological conditions
Multiple sclerosis, cerebral infarction, and brain tumors are rarely accompanied by itching. Localized pruritus is indicative of neurological causes such as compression of peripheral or central sensory nerves. This etiology of localized chronic disease can be observed in patients with postherpetic pruritus, paresthetic back pain, brachioradial pruritus, when there is a possibility of damage to the spinal cord.
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