Pruritus (itch) is an unpleasant sensory experience that evolved as a protective mechanism aimed at removing irritating agents from the skin surface, such as insects, plant substances or chemical compounds. More than 350 years ago, in 1660, the German physician Samuel Hafenreffer provided a classic definition that remained relevant for centuries: itch is an "unpleasant sensation" that arises in the body and prompts a person to scratch [1]. However, in recent years, the understanding of pruritus has substantially deepened, and in 2024, the international multidisciplinary working group IDEOM (International Dermatology Outcome Measure Itch Workgroup) adopted a new, more precise definition: "Pruritus is an unpleasant sensation of the skin and/or adjacent mucous membranes that usually elicits a desire to scratch. Pruritus can be triggered, intensified or alleviated by a wide range of external and internal factors" [2]. Chronic pruritus (CP), according to the consensus of the International Forum for the Study of Itch (IFSI), is defined as pruritus persisting for six or more weeks [2].

Chronic pruritus has long ceased to be regarded solely as a symptom of some disease. In clinical practice, it is increasingly recognized that CP may acquire its own pathophysiological mechanisms that are no longer directly related to the course of the underlying disease. Similar to chronic pain, CP at this stage may be considered an independent disease [2, 3]. This position has enormous practical significance because it explains why in some patients pruritus persists even after successful treatment of the disease that caused it. The problem of CP is multidisciplinary: it is encountered not only by dermatologists, but also by internists, gastroenterologists, nephrologists, hematologists, neurologists, psychiatrists and palliative care physicians [4]. The complexity of pathogenesis and the diversity of causes underlying CP make its diagnosis and treatment a challenging task.

The objective of this narrative literature review is to present to the physician current data on the epidemiology, pathogenesis, diagnostic algorithm and treatment of CP. In addition, for the first time in the domestic literature, the review is presented from the perspective of patient‑centered medicine: patient preferences, quality of life, shared decision‑making and therapy availability in the Russian Federation are discussed.

Data on the prevalence of chronic pruritus in the population are constantly being refined, and in recent years results from large epidemiological studies have emerged. According to the Global Burden of Disease report, pruritus is among the 50 most common symptoms that lead to a high burden of disease [6]. The prevalence of CP appears to increase with age, although population‑based studies covering all age groups are still insufficient [7].

In Germany, several large population‑based studies have been conducted. In the work of Matterne et al. (2011), the point prevalence of CP among the adult population was 13.5%, the 12‑month prevalence was 16.4%, and the lifetime prevalence was 22.0% [8]. Three years later, the same authors for the first time estimated the cumulative annual incidence of CP, which was 7%. The development of pruritus was significantly associated with older age. Multivariate analysis showed that independent predictors of CP were eczema, dry skin, bronchial asthma, liver disease, increased body mass index and high levels of anxiety [9]. In another German study involving 11,730 working individuals undergoing cancer screening, the prevalence of CP reached 16.8% [10].

The frequency of consultations for pruritus in primary care is relatively low but stable. In Australia, pruritus was the reason for 0.6% of visits to a general practitioner (excluding perinatal, periorbital and ear pruritus) [11]. In the United Kingdom, pruritus and related conditions were recorded in 1.04% of all consultations, more often in women (1.33%) than in men (0.73%) [12]. In Germany and the Netherlands, pruritus was the reason for approximately 0.7% of visits to an internist, and in most cases a skin disease was ultimately diagnosed [13].

The prevalence of CP in special populations deserves particular attention. In elderly individuals (over 65 years of age), the frequency of CP is significantly higher. It is estimated that about 60% of elderly people experience episodes of pruritus of varying severity at least once a week [14]. In a cross‑sectional study conducted in Poland among patients in a geriatric hospital, 35% of patients suffered from CP [15]. In a Turkish study involving 4,099 elderly patients, pruritus was the most common skin symptom, with a prevalence of 11.5%, reaching 19.5% in those over 85 years of age, and occurring more frequently in winter months (12.8%) [16]. According to an Egyptian study, in 73% of elderly patients with CP, pruritus was generalized, in 35% it was of moderate severity, and in 20% it worsened in winter. A dermatological cause was identified in 54% of patients, a systemic cause in 30% [17].

In pregnant women, pruritus is also a common symptom. According to a recent study, the point prevalence of pruritus during pregnancy is 20%, and the prevalence over the entire pregnancy period reaches 38% [18]. Pruritus may be a manifestation of specific dermatoses of pregnancy (polymorphic eruption, pemphigoid gestationis, intrahepatic cholestasis of pregnancy, atopic eruption of pregnancy); however, in one in five cases, pruritus is not associated with these conditions and is caused by other dermatoses coinciding with pregnancy [19, 20]. Intrahepatic cholestasis of pregnancy deserves special attention: it is characterized by intense pruritus without primary skin lesions, occurs in the third trimester and is associated with an increased risk of preterm delivery and antenatal fetal death at bile acid levels above 100 µmol/L [21].

In children, the prevalence of CP, according to an observational study of German schoolchildren, is 14.7% [22]. The main cause of CP in children is skin diseases, primarily atopic dermatitis, the cumulative prevalence of which in developed countries ranges from 5 to 22% [23]. In 3% of children, the cause of CP is chronic spontaneous urticaria [24]. In 22% of children with type 1 diabetes mellitus, pruritus is also registered, more often localized in the upper extremities (50%) and trunk (31.8%) [25].

The frequency of CP in somatic diseases varies widely. To systematize the diagnostic search, all systemic causes of CP can be presented in tabular form. Table 1 presents the main groups of systemic diseases associated with CP, their approximate frequency and key laboratory markers, which allows the internist to quickly formulate an examination plan.

Category / NosologyApproximate frequency of chronic pruritusKey laboratory markers / additional investigationsChronic kidney disease (CKD)Moderate/severe pruritus in 30% of dialysis patientsCreatinine, urea, GFR, calcium, phosphate, PTHCholestatic liver diseases (PBC, PSC, ICP)70–80%ALP, GGT, bilirubin, AMA, ASMA, autotaxin (ATX), ultrasound/MRCPHematological disorders (polycythemia, lymphomas, myeloma)15–50% (polycythemia), 30% (Hodgkin lymphoma)CBC (Ht, Hb, leukocytes, platelets), LDH, serum protein electrophoresis, JAK2 V617FEndocrine disorders (hyper‑/hypothyroidism, DM)Less than 10%TSH, free T4, fasting glucose, HbA1cIron deficiencyUp to 15% among causes of "asymptomatic" pruritusFerritin, serum iron, TIBCHIV infection13–45%HIV antibodies, viral loadParasitic infestations (toxocariasis, strongyloidiasis)Frequency varies; toxocariasis — up to 8‑12% in chronic pruritus of undetermined originEosinophilia, specific antibodies (ELISA)Notes: CKD — chronic kidney disease; GFR — glomerular filtration rate; PBC — primary biliary cholangitis; PSC — primary sclerosing cholangitis; ICP — intrahepatic cholestasis of pregnancy; DM — diabetes mellitus; PTH — parathyroid hormone; ALP — alkaline phosphatase; GGT — gamma‑glutamyl transferase; AMA — antimitochondrial antibodies; ASMA — anti‑smooth muscle antibodies; ATX — autotaxin, lysophospholipase D; CBC — complete blood count; Ht — hematocrit; Hb — hemoglobin; LDH — lactate dehydrogenase; TIBC — total iron‑binding capacity; ELISA — enzyme‑linked immunosorbent assay; MRCP — magnetic resonance cholangiopancreatography.

In chronic kidney disease (CKD) at end‑stage, according to the DOPPS study, moderate or severe CP is observed in 30% of patients on hemodialysis [26]. In 43.5% of patients, the skin appears normal (IFSI group II), in 37.9% there are secondary scratch lesions, including prurigo nodularis (group III), and only in 18.6% is there a primary skin disease (group I) [27]. The three‑year cumulative incidence of CP in hemodialysis patients is about 17% [28]. In liver diseases with cholestasis (primary biliary cholangitis, primary sclerosing cholangitis), the frequency of CP reaches 70–80%, and pruritus may precede jaundice by years [29, 30]. In polycythemia vera, pruritus occurs in 15‑50% of patients, and in half of cases it is aquagenic (occurring after contact with water) [31]. In Hodgkin lymphoma, the prevalence of pruritus is about 30% [32]. Among patients with HIV infection, CP is registered in 13‑45% and may be the first manifestation of infection [33]. In diabetes mellitus, pruritus occurs in 11‑18% of patients, more often as localized genital pruritus [34]. In a prospective French study of 95 patients with "pruritus without rash," a systemic cause was identified in 40% of cases, with the most frequent causes being toxocariasis (8 cases), hematological diseases (7 cases), CKD (6 cases), hypothyroidism (5 cases) and iron deficiency (5 cases). Malignant neoplasms were found in 8.42% of cases [35].

The association of CP with hematological malignancies deserves special attention. In a cohort study involving 327,502 patients with undifferentiated pruritus, it was shown that the risk of detecting hematological cancer within the first year was increased: hazard ratios were 4.42 for Hodgkin lymphoma, 2.56 for myeloid leukemia, 2.38 for multiple myeloma, and 2.35 for non‑Hodgkin lymphomas [36]. In a Danish cohort study, the absolute annual cancer risk in patients with pruritus was 1.63%, and the observed number of hematological and solid cancers was 13% higher than expected [37]. These data underscore the importance of thorough cancer screening in patients with CP, especially in the absence of an obvious dermatological cause.

Patient‑centered aspect: the epidemiological data presented should be discussed with the patient in an accessible manner to explain the need for diagnostic work‑up. A patient with CP should understand that pruritus may be not simply "nervous," but a marker of a treatable systemic disease (iron deficiency, thyroid disease), and that early diagnosis improves prognosis.

Pathogenesis of chronic pruritus

Understanding the pathogenesis of CP has undergone dramatic changes over the past two decades. Whereas histamine was previously considered the main mediator of pruritus, and therapy was built around antihistamines, it is now clear that histamine plays a key role only in a limited number of conditions (urticaria, insect bite reactions, drug allergic reactions). In most forms of CP, non‑histaminergic pathways predominate [38, 39]. The modern concept of CP pathogenesis views it as the result of a complex interaction between skin cells (keratinocytes, mast cells), immune cells and sensory nerve endings, involving both the peripheral and central nervous systems [40].

Peripheral component of pathogenesis. The process begins in the epidermis and at the dermo‑epidermal junction, where a pruritogen — a substance that causes itching — activates receptors on unmyelinated C‑nerve fibers [41]. These fibers are subdivided into histaminergic and non‑histaminergic depending on receptor expression. Histaminergic fibers predominantly participate in transmitting acute pruritus, whereas CP is associated with non‑histaminergic fibers [39].

Keratinocytes play a key role in peripheral sensitization and are considered the "front line" of the nervous system. Keratinocytes express a wide range of receptors, including PAR‑2 (protease‑activated receptor), TLR3, histamine H1‑H4 receptors, endothelin receptors (ETA and ETB), serotonin receptors (5‑HTR), oncostatin M receptor (OSMRβ), TSLP receptor, and TRP channels (TRPV3, TRPV4) [41]. When the epidermal barrier is disrupted, keratinocytes release pro‑inflammatory cytokines (IL‑6), chemokines (CXCL‑8, CCL17, CCL19, CCL22, CCL23, CCL4, CXCL1), and nerve growth factor (NGF). The most important pruritogenic mediators released by keratinocytes and capable of directly activating nerve endings are TSLP (thymic stromal lymphopoietin), periostin, endothelin‑1 (ET‑1), IL‑33, and brain natriuretic peptide (BNP) [42].

TSLP, whose levels are significantly elevated in atopic dermatitis, activates sensory neurons via the TRPA1 channel and initiates a cascade of Th2‑mediated inflammation [40]. Periostin, released by keratinocytes and fibroblasts under the influence of IL‑13 and IL‑4, activates integrin αVβ3 on sensory fibers and enhances TSLP release, forming a positive feedback loop [42]. Endothelin‑1 is one of the most potent pruritogens of keratinocyte origin; its production is stimulated by activation of PAR‑2, TLR3, TRPV3 and TRPV4 [41].

Mast cells, located in the papillary dermis near nerve fibers, are another key source of pruritogens. They release histamine, tryptase, prostaglandins, leukotrienes and cytokines, activating both histaminergic and non‑histaminergic pathways [43]. Merkel cells, interacting with MRGPRA3+ pruriceptive endings, also participate in pruritus, especially in xerosis and prurigo nodularis, and express TRPM8 [41].

Receptors and ion channels. Three main classes of pruritus receptors are distinguished: G protein‑coupled receptors (GPCRs), Toll‑like receptors (TLRs), and cytokine receptors (IL‑31, TSLP, IL‑4, IL‑13, IL‑33, oncostatin M) [44]. Among GPCRs, Mas‑related GPCRs (MRGPRs), particularly MRGPRX1 and MRGPRX4 in humans, are of special importance. For example, chloroquine induces pruritus through stimulation of MRGPRA3 in rodents and MRGPRX1 in humans [44].

TRP channels (transient receptor potential channels), primarily TRPV1 (vanilloid 1) and TRPA1 (ankyrin 1), play a key role in transmitting the itch signal. These channels are activated after binding of a pruritogen to the receptor, allow calcium ions to enter the cell, and generate an action potential. The histaminergic pathway depends on TRPV1, whereas the non‑histaminergic pathway is largely mediated by TRPA1 [44].

Cytokines and the neuro‑immune axis. A major discovery in recent years has been the understanding of the role of Th2‑type cytokines in the pathogenesis of CP. Interleukin‑31 (IL‑31) occupies a special place; it is produced by type 2 T‑helper cells, mast cells, macrophages and eosinophils. IL‑31 binds to the heterodimeric receptor IL‑31RA/OSMRβ, expressed on sensory neurons, keratinocytes and immune cells. Activation of this receptor leads to the release of BNP and somatostatin in neurons, as well as to disruption of the skin barrier function [45]. IL‑31 levels are elevated in the skin and serum of patients with atopic dermatitis and prurigo nodularis, and the degree of elevation correlates with pruritus intensity [46].

IL‑33, a member of the IL‑1 family, is constitutively expressed in the nuclei of keratinocytes and is released as an "alarmin" upon cell damage or inflammation. Its receptor ST2 is expressed not only on immune cells but also on sensory nerve endings, and activation of this receptor induces pruritus [42]. IL‑33 plays an important role in pruritus associated with dry skin and in CP of undetermined origin [5].

TSLP, produced by keratinocytes, is a potent activator of Th2 inflammation. It directly activates sensory neurons via TRPA1, bypassing TRPV1, and induces periostin release, which in turn enhances TSLP production, forming a pruritogenic positive feedback loop [42].

IL‑4 and IL‑13, typical Th2 cytokines, also play an important role in pruritus. Both cytokines activate sensory neurons through the common IL‑4Rα subunit, and this effect depends on JAK1 and TRP channels. This mechanism underlies the action of dupilumab — an antibody to IL‑4Rα that effectively relieves pruritus in atopic dermatitis and prurigo nodularis [47].

Neuropeptides. Substance P (SP) is one of the most studied neuropeptides involved in pruritus. SP is released from primary sensory nerves and immune cells (macrophages, eosinophils, basophils) and binds to the neurokinin‑1 receptor (NK1R) on mast cells, keratinocytes and endothelium. This leads to mast cell degranulation with the release of histamine, prostaglandin D2, tumor necrosis factor α and leukotriene B4, which clinically manifests as erythema, wheals and pruritus [48]. Aprepitant, an NK1R antagonist, has shown efficacy in various forms of CP, although the results of clinical trials have not always been consistent.

Calcitonin gene‑related peptide (CGRP) is also involved in neurogenic inflammation and pruritus, although its role is less studied. CGRP is released from sensory neurons after TRPV1 activation and acts on T and B cells, dendritic cells, mast cells and keratinocytes, causing neurogenic vasodilation and immune responses [42].

Opioid system. Opioid peptides play a complex role in the regulation of pruritus. Activation of μ‑opioid receptors (MOR) enhances pruritus (this is well known from the side effect of morphine), whereas activation of κ‑opioid receptors (KOR) suppresses it. Normally, there is a homeostasis between MOR and KOR, maintained mainly by the release of dynorphin — an endogenous KOR agonist [49]. In CP, especially in CKD and cholestasis, this balance is disrupted toward a predominance of MOR tone. Thus, in hemodialysis patients with CP, significantly lower KOR expression has been found in the skin compared with non‑pruritic patients, and KOR expression negatively correlated with pruritus intensity [50].

Transmission of pruritus in the spinal cord and central nervous system. The pruritus signal from peripheral nerves is transmitted through neuronal cell bodies in the dorsal root ganglia to the dorsal horn of the spinal cord. Here, GRP‑positive interneurons (gastrin‑releasing peptide) play a key role; they activate GRPR neurons, which transmit the signal further. Somatostatin and neurokinin B are also involved in nociceptive and pruriceptive pathways [51]. It is important to note the existence of descending inhibitory pathways from the brainstem that modulate pruritus at the spinal level. These pathways, involving norepinephrine and serotonin, appear to be disrupted in patients with CP [51]. In the brain, pruritus processing involves the primary and secondary somatosensory cortex, insula and anterior cingulate cortex, and activation patterns in patients with CP differ from those in healthy volunteers [52].

Patient‑centered aspect: understanding the pathogenesis allows explaining to the patient why antihistamines may not help (non‑histaminergic pruritus) and why more complex treatment regimens are required. It is also important to discuss with the patient the psychosomatic component: stress can exacerbate pruritus through activation of neuropeptides, and conversely, relaxation methods may be beneficial.

IFSI clinical classification. The International Forum for the Study of Itch (IFSI) proposed a classification based on the condition of the skin at the time of pruritus onset [2]. This classification is of key importance for the diagnostic search, as different groups imply a different spectrum of causes.

Group I (IFSI I) — pruritus on primarily altered (inflamed) skin. This group includes patients in whom pruritus appeared simultaneously with primary morphological elements: macules, papules, vesicles, wheals, etc. Differential diagnosis in this group is conducted within dermatological diseases: atopic dermatitis, psoriasis, urticaria, scabies, and many others [2].

Group II (IFSI II) — pruritus on primarily unaltered skin. This is the most challenging group for the internist, as the cause of pruritus may be systemic (kidney, liver, blood diseases, endocrine disorders), neurological, psychogenic or drug‑induced. The skin may appear normal or have secondary changes caused by scratching [2]. The term "pruritus sine materia" was previously used for this group, but it is not recommended in modern practice [2].

Group III (IFSI III) — pruritus with chronic secondary scratch lesions. This group includes patients with pronounced secondary changes (excoriations, lichenification, prurigo nodularis nodules) that mask or completely replace the primary elements. Diagnosis in this group requires special attention, as the cause may belong to any of categories I‑II [2].

Etiological classification. In addition to clinical grouping, IFSI proposed an etiological classification, distinguishing the following categories of CP [2]:

Differential diagnosis in group II. For the internist, the most challenging is group II (pruritus on unaltered skin). Key elements of differential diagnosis are detailed history‑taking, assessment of localization and timing of pruritus, and targeted laboratory investigation. To simplify this process, Table 2 presents the most characteristic anamnestic and clinical "keys" for various forms of CP, allowing a suspicion of a particular cause already at the history‑taking stage.

Characteristic of pruritus / TriggerMost likely causeAdditional commentsAquagenic pruritus (after contact with water of any temperature)Polycythemia vera (up to 50% of patients), less commonly — xerosis, drug‑induced pruritusPruritus occurs 5‑15 minutes after contact, may last up to 60 minutes. Associated with JAK2 V617F mutation.Pruritus triggered by physical exertion, with small whealsCholinergic urticariaWheals are 1‑3 mm in diameter, surrounded by erythema. Occur with increased body temperature (sports, hot shower, emotions).Nocturnal generalized pruritus + fever + night sweats + weight lossLymphoma (especially Hodgkin lymphoma)These symptoms require urgent investigation (CBC, LDH, lymph node ultrasound, chest radiography).Pruritus worsening at rest and upon warming (blanket, warm clothing)Cholestatic pruritus, uremic pruritusTypical of systemic causes. Relief of pruritus with cold is an important diagnostic sign.Seasonal pruritus (winter)Xerotic eczema ("winter itch"), atopic dermatitis, psoriasisAssociated with low air humidity and use of central heating.Localization: interscapular area (unilateral)Notalgia paresthetica (neuropathy)Often accompanied by hyperpigmentation and lichenification. MRI of the thoracic spine may reveal root compression.Localization: lateral surface of forearms and armsBrachioradial pruritus (neuropathy)Often associated with C5‑C6 root compression. Characteristic "ice pack sign" (relief with cooling).Localization: palms and solesCholestatic pruritus (early stage)Skin may be without visible changes. Requires exclusion of liver and biliary tract diseases.Localization: anogenital areaDiabetes mellitus, iron deficiency, pinworms (children), candidiasisExamination, smear for Candida, stool examination for helminth eggs, ferritin, glucose required.Localization: scalp (without rash)Depression, anxiety disorder, somatoform pruritusDiagnosis of exclusion. Requires psychiatric/psychotherapeutic consultation after exclusion of dermatological (seborrheic dermatitis, psoriasis) and systemic causes.Pruritus after ingestion of hot food, alcohol, coffeeVasodilation (trigger factor)Can exacerbate any pruritus, but especially characteristic of neuropathic forms and essential pruritus of the elderly.

Anamnestic features of diagnostic significance [53]:

Localization of pruritus (see also Table 2) [53]:

Role of drugs. Almost any drug can cause pruritus, with or without eruptions. Drug‑induced CP without visible eruptions accounts for approximately 5% of all adverse cutaneous reactions [54]. The most common culprits are ACE inhibitors, antibiotics (especially penicillins), antiarrhythmic agents (amiodarone), diuretics, statins, opioids, antimalarial drugs (chloroquine, hydroxychloroquine), and antineoplastic agents — EGFR inhibitors, PD‑1 inhibitors, imatinib [54]. Hydroxyethyl starch (HES) should be mentioned separately; it causes generalized or localized CP in 12‑42% of patients, persisting on average for 15 months after discontinuation [55].

Patient‑centered aspect: when taking the history, it is important to specifically ask the patient about all medications taken, including over‑the‑counter drugs, dietary supplements and herbal remedies, as patients often do not associate pruritus with a "habitual" drug. Shared decision‑making regarding possible discontinuation or substitution of a drug requires discussion of risks and benefits.

Diagnosis of chronic pruritus should be systematic and stepwise. The key principle is: pruritus is a symptom, not a diagnosis, so the physician's task is to find its cause. The 2025 European guideline proposes the following algorithm [53].

Step 1 (mandatory screening). Every patient with CP, regardless of the presumed cause, should undergo the following minimum laboratory screening [53]:

In addition, a thorough examination of the entire skin (including the scalp, nails, mucous membranes and anogenital area) should be performed to look for primary lesions, as well as a physical examination with palpation of lymph nodes, liver and spleen [53].

Step 2 (if the cause is not found). If after Step 1 the cause of CP has not been established, proceed to Step 2 [53]:

Step 3 (advanced investigation). If the first two steps have not identified the cause, specialized investigation is conducted depending on clinical suspicion [53]:

If after the entire volume of investigation the cause of pruritus remains unidentified, the diagnosis "chronic pruritus of undetermined origin" is justified. Importantly, however, such patients should be reassessed periodically, as the cause may become evident later [2, 53].

Patient‑centered aspect: the diagnostic work‑up should be discussed with the patient to avoid unrealistic expectations and anxiety. The patient should be explained that absence of a diagnosis after the first step does not mean that "nothing serious is wrong," and that the investigation plan will be stepwise. It is also important to take into account the patient's financial capabilities when prescribing expensive methods (MRI, genetic testing) and to offer alternatives within the compulsory health insurance system where possible.

Treatment of CP should be multi‑level, stepwise and strictly individualized. It includes: etiotropic therapy (treatment of the underlying disease), general measures and skin care, topical therapy, systemic pharmacotherapy and psychosomatic support [53]. The most important principle of patient‑centered medicine is shared decision‑making: the physician informs the patient about available treatment options, their efficacy, side effects, cost and availability, and the patient expresses their preferences and values.

General measures and skin care. This step is mandatory for all patients with CP, regardless of the presumed cause [53]. The following recommendations are given to the patient:

Patient‑centered aspect: skin care recommendations should not only be listed but also demonstrated (e.g., showing how to properly apply an emollient). It is important to find out from the patient which products they have already tried and to help choose products that are affordable and convenient to use. For elderly patients with limited mobility, spray emollients may be recommended instead of creams in jars.

Topical therapy. For localized forms of CP or when rapid symptomatic control is needed, topical agents are used [53]:

Menthol (1‑10%) and camphor — activate TRPM8 and TRPV3 channels respectively, producing a cooling sensation and a "distracting" effect. Menthol at a concentration of 1‑3% is safe and effective in various forms of CP, including atopic dermatitis and xerosis. The European guideline recommends topical use of menthol and its derivatives [53].

Capsaicin (0.025‑0.075%) — an agonist of TRPV1. With repeated application, it causes desensitization and depletion of neuropeptides (primarily substance P) in nerve endings, leading to a prolonged antipruritic effect. It is effective in localized neuropathic forms of CP — notalgia paresthetica, brachioradial pruritus, postherpetic neuralgia, as well as in psoriasis and CKD‑associated pruritus [58, 59]. The main drawback is burning upon first application, which can be reduced by prior cooling of the skin or use of a local anesthetic.

Topical glucocorticosteroids (GCS) — indicated only in the presence of an inflammatory dermatosis. On unaltered skin (e.g., in systemic causes), GCS are not recommended due to lack of effect and risk of skin atrophy. In dermatoses, they are used in short courses (1‑3 weeks) with strength selection depending on localization [53].

Topical calcineurin inhibitors (tacrolimus 0.03‑0.1%, pimecrolimus 1%) — effective in localized pruritus on thin skin (face, genitals, intertriginous areas), especially in atopic dermatitis, seborrheic dermatitis, lichen planus, and lichen sclerosus. Burning and stinging may occur upon first application (TRPV1 activation), which usually resolve within 5‑10 days of regular use [60].

Patient‑centered aspect: when prescribing capsaicin, the patient should be warned about burning and taught how to reduce discomfort (cooling, starting with a low concentration). Patients often discontinue treatment due to expecting immediate effect, so it is important to discuss realistic timelines (for capsaicin — 1‑2 weeks before effect appears).

Systemic pharmacotherapy. Systemic agents are prescribed when topical therapy and general measures are ineffective, as well as in generalized forms of CP. The choice of agent depends on the presumed cause and clinical situation. It is critically important to consider age, comorbidity, concomitant therapy, and patient preferences (e.g., willingness to receive injections, fear of "hormonal" drugs).

Antihistamines. It is important to emphasize that antihistamines have a very limited role in the treatment of CP. They are effective only in histaminergic pruritus, i.e., in urticaria (acute and chronic), mastocytosis, and insect bite reactions. In most other forms of CP (uremic, cholestatic, neuropathic, psychogenic), they are ineffective [61]. Second‑generation antihistamines (cetirizine, loratadine, fexofenadine, desloratadine, bilastine, rupatadine) are preferred over first‑generation agents due to less sedative effect and better safety profile [53]. First‑generation antihistamines (diphenhydramine, hydroxyzine, chlorpheniramine) should not be routinely used in elderly patients due to the risk of falls, confusion, cognitive impairment and anticholinergic effects. In a prospective cohort study, their long‑term use was associated with an increased risk of dementia [62].

Patient‑centered aspect: the patient should be explained that antihistamines help only in certain types of pruritus (allergic), and if there is no effect within 2‑4 weeks, they should be discontinued rather than increasing the dose indiscriminately.

Opioid modulators. This is one of the most significant breakthroughs in the treatment of CP in recent years.

Naltrexone — a μ‑opioid receptor antagonist, administered orally at a dose of 50‑150 mg/day. Most effective in cholestatic pruritus (primary biliary cholangitis, primary sclerosing cholangitis). In double‑blind placebo‑controlled trials, naltrexone significantly reduced pruritus intensity [63]. In uremic pruritus, results are conflicting: some studies show a positive effect, others show no effect [64].

Patient‑centered aspect: when prescribing naltrexone, it is necessary to warn about possible nausea and dizziness, and recommend starting with half a dose.

Gabapentin is the drug of choice for neuropathic forms of pruritus — brachioradial pruritus, notalgia paresthetica, postherpetic neuralgia, small‑fiber neuropathy. In CKD‑associated pruritus, gabapentin at a dose of 300 mg three times weekly after dialysis significantly reduces pruritus intensity compared with placebo [65]. At the same time, in a retrospective analysis of data from more than 10,000 hemodialysis patients, gabapentin use was associated with a higher risk of falls, fractures and confusion; therefore, these drugs should be prescribed with caution, especially in elderly patients [66].

Patient‑centered aspect: the patient should be warned about the sedative effect and dizziness, especially at the start of therapy. It is recommended to start with a low dose (gabapentin 100‑300 mg at night) and titrate slowly. In the elderly, measures to prevent falls should be discussed. Drivers should be advised to refrain from driving during the titration period.

Antidepressants. Antidepressants play an important role in the treatment of CP not only in psychogenic cases, but also in other forms, as they modulate descending serotonergic and noradrenergic itch control pathways. The evidence base is strongest for the following drugs [67]:

Paroxetine (20‑40 mg/day) — the most studied selective serotonin reuptake inhibitor (SSRI) in CP. Effective in paraneoplastic pruritus, CP of undetermined origin, pruritus associated with polycythemia vera, and psychogenic pruritus [68, 69].

Mirtazapine (15‑30 mg at night) — a tetracyclic antidepressant with α2‑antagonist activity. Particularly useful in nocturnal pruritus due to its sedative effect, and in patients with comorbid depression and weight loss [70].

Sertraline (75‑100 mg/day) — effective in cholestatic pruritus (adults and children) and, according to some data, in CKD‑associated pruritus [71, 72]. The antipruritic effect of antidepressants does not develop immediately, usually after 2‑3 weeks, with a maximum reached at 4‑6 weeks [67].

Patient‑centered aspect: patients often fear prescription of antidepressants because of the stigma of "psychiatric" drugs. It should be explained that in this case antidepressants are used not to treat depression (although it may be comorbid), but to act on neural pathways controlling pruritus. The delayed effect (2‑4 weeks) and possible side effects (nausea, headache, sedation, weight gain with mirtazapine) should be discussed.

Biologic agents. In recent years, biologics have revolutionized the treatment of CP in certain dermatological conditions and in prurigo nodularis [63].

Dupilumab — a monoclonal antibody to the α‑subunit of the IL‑4 receptor, blocking IL‑4 and IL‑13 signaling pathways. Initially approved for atopic dermatitis, then for prurigo nodularis. In two phase III RCTs in patients with prurigo nodularis (LIBERTY‑PN PRIME and PRIME 2), dupilumab significantly reduced pruritus intensity by week 12, and by week 24, 59% of patients achieved clinically significant reduction (≥4 points on WI‑NRS) [73, 74]. In real‑world clinical practice, dupilumab has also shown efficacy in patients with CP of undetermined origin [75].

Omalizumab — an anti‑IgE antibody, effective only in chronic spontaneous urticaria, where it significantly reduces pruritus intensity [76]. It is not indicated for other forms of CP.

Patient‑centered aspect: prescription of biologics requires detailed discussion with the patient about the route of administration (subcutaneous injections), frequency (every 2‑4 weeks), duration of therapy (at least 6 months), expected efficacy (reduction of pruritus by 4+ points by week 12‑16), and side effects (conjunctivitis with dupilumab). It is also important to discuss drug availability (concessionary provision, regional availability). Shared decision‑making includes assessment of the patient's readiness for injections and long‑term therapy.

JAK inhibitors. JAK inhibitors are small molecules that block intracellular signaling from many cytokines, including IL‑4, IL‑13, IL‑31, TSLP, and others. They have a rapid antipruritic effect (already 1‑3 days after initiation) [77].

Abrocitinib (200 mg/day) and upadacitinib (15‑30 mg/day) are approved for the treatment of atopic dermatitis, including pruritus control. In a head‑to‑head comparison with dupilumab, both drugs showed faster (from week 1) and more pronounced reduction of pruritus in the first weeks of treatment; however, by week 16 the differences leveled off [78]. In prurigo nodularis and CP of undetermined origin, preliminary positive data on abrocitinib are available [79]. It is important to note that JAK inhibitors carry potential risks: serious infections, thromboembolic complications, cardiovascular events and malignancies. These risks are higher in elderly patients and patients with risk factors; therefore, the drugs require careful patient selection and monitoring [80].

Patient‑centered aspect: the patient should be thoroughly informed about the risks of JAK inhibitors, especially thrombosis and infections. Shared decision‑making includes an assessment of the risk/benefit ratio in each individual case. In elderly patients with cardiovascular risk factors, JAK inhibitors are not first‑line drugs.

Phototherapy. Ultraviolet phototherapy (narrow‑band UVB 311 nm, UVA1, PUVA) is an effective treatment modality for CP, especially in dermatological forms (atopic dermatitis, psoriasis, cutaneous T‑cell lymphoma), as well as in CKD‑associated and cholestatic pruritus [81]. The mechanism of action includes induction of mast cell apoptosis, reduction of intraepidermal nerve fiber density, and suppression of IL‑31 and other cytokines [82]. In a retrospective study of 102 patients with CP of various origins, a significant reduction in pruritus intensity and improvement in quality of life were noted after only 4 weeks of phototherapy, regardless of skin phototype [83]. In CKD‑associated pruritus, UV therapy has been used for decades, although a recent RCT did not confirm its superiority over placebo, leaving the question open [84].

Patient‑centered aspect: phototherapy requires regular visits (2‑3 times per week for several weeks), which may be difficult for working patients or those with limited mobility. The logistics (proximity to home, transportation) and the possibility of receiving procedures under compulsory health insurance should be discussed. The patient should also be warned about skin phototype and the risk of burns.

Psychosomatic therapy and rehabilitation. Chronic pruritus has a profound impact on patients' quality of life, comparable to that of chronic pain. In a European multicenter study, dermatological patients with pruritus had higher levels of depression, anxiety, sleep disturbance and economic difficulties compared with patients without pruritus [85]. In another study, suicidal ideation was registered in 18.5% of patients with severe CP [86].

Therefore, psychosomatic support is an obligatory part of treatment [87]. The most effective are structured educational programs that include information on the nature of pruritus, training in distraction techniques, relaxation, and breaking the vicious "itch‑scratch" cycle. The "habit reversal" technique — conscious suppression of scratching and its replacement with an alternative action (clenching the fist, stroking the skin) — has shown efficacy in children and adults with atopic dermatitis [88].

Patient‑centered aspect: it is important to explain to the patient that pruritus has not only a physical but also a psychological component, and that learning self‑control techniques does not mean that "it's all in the head." Together with the patient, accessible methods can be chosen: breathing exercises, listening to music, tactile distraction (stroking a smooth stone). A pruritus diary can be used to assess effectiveness.

In accordance with the principles of patient‑centered medicine, the evaluation of treatment efficacy should include not only objective clinical parameters but also subjective patient‑reported outcomes (PROs). For CP, the following validated instruments are available:

Patient‑centered aspect: before starting treatment and at follow‑up (every 4‑8 weeks), it is recommended to assess pruritus intensity by NRS/VAS and quality of life using ItchyQOL or DLQI. This allows objectification of the response to therapy and adjustment of treatment. The patient should be explained the purpose of filling out the questionnaires and the results discussed.

Elderly patients. Treatment of CP in elderly patients presents particular challenges due to comorbidity, polypharmacy and age‑related skin changes [93]. Most elderly patients have some degree of xerosis, so emollients are the mainstay of therapy. First‑generation antihistamines are contraindicated due to anticholinergic effects (urinary retention, constipation, confusion, falls) [94]. Tricyclic antidepressants (doxepin, amitriptyline) are also not recommended in the elderly due to similar risks. Gabapentin is effective but requires titration from low doses (100 mg at night) due to the risk of sedation and ataxia [66]. Selective serotonin reuptake inhibitors (paroxetine, sertraline) are generally safe but may cause hyponatremia and gastrointestinal disturbances. Phototherapy is a good alternative, avoiding systemic drug burden; however, it is contraindicated in patients with a history of skin cancer [53].

Patient‑centered aspect: in elderly patients, it is especially important to consider cognitive and physical limitations. For example, emollients in spray or tube creams are more convenient for patients with arthritis. The treatment regimen should be simplified (e.g., "apply the cream once a day after shower" rather than "apply 3‑4 times a day"). Measures to prevent falls with gabapentin should be discussed with the patient and caregivers.

Pregnant women. In treating pruritus in pregnancy, priority is given to topical therapy and addressing the cause (e.g., ursodeoxycholic acid in intrahepatic cholestasis of pregnancy). Emollients with urea and menthol are considered safe [95]. Among antihistamines, loratadine and cetirizine have the best safety evidence base and can be used from the second trimester [96]. First‑generation antihistamines should be avoided. Phototherapy (UVB) is safe but requires monitoring of folic acid levels [97]. Systemic GCS, cyclosporine and azathioprine are used only for life‑saving indications in severe dermatoses of pregnancy. It should be remembered that intrahepatic cholestasis of pregnancy requires urgent determination of bile acids and delivery at levels >100 µmol/L [21].

Patient‑centered aspect: pregnant patients often experience anxiety about the safety of treatment for the fetus. The risk/benefit ratio should be explained in detail, and topical agents with the least systemic absorption recommended. It is important to discuss that untreated intense pruritus may also be harmful (sleep disturbance, stress, risk of preeclampsia in cholestasis).

Children. In children, the causes of CP are most often atopic dermatitis, scabies and urticaria. Therapy should be as safe as possible. Topical GCS of low and medium potency are used in short courses. Tacrolimus 0.03% and pimecrolimus 1% are approved from 2 years of age (in some countries from 3 months) [98]. Second‑generation antihistamines are the drugs of choice for urticaria. First‑generation antihistamines are not recommended for long‑term use due to effects on cognitive function and school performance [99]. Phototherapy is possible, but the potential risk of skin cancer with long‑term use should be considered. The JAK inhibitor upadacitinib is approved in pediatrics from 12 years of age for atopic dermatitis [77].

Patient‑centered aspect: when treating children, parents should be involved in the decision‑making process. Not only efficacy but also convenience of application (e.g., once daily instead of three times) should be discussed. It is also important to teach the child distraction and relaxation techniques (e.g., "pet the kitty instead of scratching"). For adolescents, discussion of the cosmetic acceptability of products and the impact of treatment on social life is relevant.

Chronic pruritus is a common interdisciplinary problem that may be not only a distressing symptom but also an early marker of serious somatic and hematological diseases. Internists and dermatologists should be familiar with the main causes of CP and be proficient in the diagnostic algorithm, which begins with mandatory laboratory screening (Table 1) and use of anamnestic "keys" (Table 2). Therapy should be stepwise, including treatment of the underlying disease, intensive skin care with emollients, and, if necessary, pathogenetic systemic therapy. The emergence of new drug classes — biologics (dupilumab) and JAK inhibitors (abrocitinib, upadacitinib) — has significantly expanded the treatment options for even the most refractory forms of CP; however, these drugs require appropriate patient selection and safety monitoring. Psychosomatic support and patient education are essential components of CP management.

This review has several limitations. First, it is not systematic, which allows for the possibility of selective citation. Second, most data are derived from foreign studies, and their applicability to the Russian population may require confirmation in local studies. Third, no meta‑analysis was performed, so quantitative estimates of efficacy are provided as approximate. Despite these limitations, the review reflects the most current information as of 2026 on the problem of CP and can be used for clinical practice and education.