Abstract
Pruritus affects millions of patients with skin and systemic diseases. Chronic pruritus is defined as an itch that lasts more than 6 weeks. It has a significant impact on the quality of life and sleep of patients. It can occur without any primary skin eruption associated with underlying systemic diseases such as end-stage renal failure, cholestatic liver disease, hepatitis C, and HIV viral infection. It could be a presenting symptom in lymphoproliferative disorders such as polycythemia vera and lymphoma. It can also occur in relation to primary damage to nerve fibers, such as postherpetic neuropathy, small-fiber neuropathy in diabetes, and spinal nerve injuries as well as psychogenic causes such as depression. There are no specific drugs that benefit all forms of pruritus. Treatments are divided into topical and systemic. Topical treatments are particularly helpful for pruritus resulting from skin inflammation. Systemic antipruritics include oral antihistamines, such as first-generation H 1 antihistamines for urticaria. In the majority of chronic itch conditions antihistamines do not relieve itch. Drugs that are used for neuropathic pain such as gabapentin and pregabalin and selective serotonin reuptake inhibitors reduce itch intensity, in particular neuropathic itch. New therapies include κ-opioid drugs and μ antagonists such as butorphanol.
Keywords
Chronic pruritus, Itch pathophysiology, Neuropathic pruritus, Psychogenic itch, Systemic pruritus
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Chronic itch can occur without primary skin rash associated with underlying systemic diseases.
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Itch can be the presenting symptom of lymphoma and hepatic diseases.
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Chronic systemic itch is associated with imbalance of μ versus κ opioids.
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Topical antipruritic treatments include local anesthetics, coolants, emollients, and topical immunomodulators.
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Systemic antipruritic treatments include drugs that are used for neuropathic pain, such as gabapentin, pregabalin, selective serotonin reuptake inhibitors, and κ opioids.
Pruritus is a complex symptom that is very similar to pain and affects all humans in the course of their lives. Chronic pruritus is defined as an itch that lasts more than 6 weeks. It has a significant impact on patients’ quality of life, very similar to chronic pain. It is the primary symptom in a diverse range of inflammatory skin diseases, such as atopic eczema, psoriasis, dry skin, and chronic urticaria ( Table 13-1 ). It can occur without any primary skin eruption associated with underlying systemic diseases ( Table 13-2 ), and can be the presenting symptom of lymphoma, hepatic diseases such as biliary cirrhosis and hepatitis C, and HIV viral infections. It can occur in relation to primary damage to nerve fibers, such as postherpetic neuropathy, as well as spinal nerve root injuries such as brachioradial pruritus and notalgia paresthetica, and in afferent nerves in the central nervous system post stroke. Pruritus is a common symptom in psychiatric diseases such as obsessive compulsive disorders, depression, and in delusions of parasitosis.
| Atopic eczema |
| Psoriasis |
| Contact dermatitis |
| Urticaria |
| Dry skin |
| Elderly idiopathic itch |
| Seborrheic dermatitis |
| Lichen planus |
| Cutaneous T-cell lymphoma |
| Scars and post burns |
| Pityriasis rosea |
| Bullous pemphigoid (including the prebullous phase) |
| Dermatitis herpetiformis |
| Pregnancy-associated cutaneous eruptions |
| Superficial fungal diseases |
| Folliculitis |
| Scabies |
| HIV |
| Varicella |
| Onchocerciasis |
| End-stage chronic renal disease |
| Cholestasis Primary biliary cirrhosis Hepatitis C viral infection Cholestasis of pregnancy |
| Hematopoietic Hodgkin’s lymphoma Non-Hodgkin’s lymphoma Mastocytosis Multiple myeloma Polycythemia vera Iron deficiency anemia Myeloid and lymphocytic leukemias Myelodysplastic disorders |
| Solid malignant tumors (paraneoplastic manifestation) |
| Endocrine Hyperthyroidism Diabetes Mastocytosis Anorexia nervosa |
| Drugs (such as opioids, hydroxyethyl starch, chloroquine, epidermal growth factor inhibitors, and ipilimumab) |
| Connective tissue diseases Dermatomyositis Scleroderma Sjögren’s syndrome |
| Itch in post-transplant patients |
| Peripheral neuropathy Postherpetic neuralgia Brachioradial pruritus Notalgia paresthetica Diabetic neuropathy |
| Central nervous system neuropathy Multiple sclerosis Brain tumors Cerebrovascular events Creutzfeldt–Jakob disease |
| Psychogenic itch Depression Obsessive compulsive disorder Fibromyalgia Delusional state of parasitophobia disorder |
Skin Signs of Chronic Pruritus
There are common skin lesions that develop in pruritus as a result of repetitive scratching and rubbing of the skin. These lesions are not considered a primary skin eruption. They include excoriations such as prurigo nodules (excoriated papules that lead to nodule formation). These are usually distributed on the extensor side of the limbs and upper back. Lichenification is a thickened plaque with marked accentuation of the skin creases, which develops as a result of continuous rubbing and scratching, generally in areas that the patient can easily scratch and rub, such as the nape of the neck, below the elbow, the ankle, the buttocks, and the genitalia. Changes in skin pigmentation—both hyper- and hypopigmentation—can occur because of repeated scratching. Excoriated lesions resulting from repetitive scratching, as well as primary eczematous lesions, can become infected, particularly in patients with atopic dermatitis.
The middle of the back, which cannot be easily reached, may show normal skin or relative hypopigmentation, in contrast to the hyperpigmentation of the areas subjected to persistent scratching, thereby resulting in a butterfly pattern. The finger nails may be shiny because of prolonged rubbing.
Diagnosis
When no diagnosis of a primarily dermatological disorder can be made, a history, review of systems, physical examination, and screening laboratory examination are needed.
A detailed history is important. One should investigate whether the patient suffers from generalized or localized itching. A localized itch may be associated with a burning sensation and pain in peripheral neuropathy, such as damage to cervical spinal nerve roots in brachioradial pruritus or thoracic nerve roots in notalgia paresthetica. Careful history also includes a drug history, as drugs such as opiates, aspirin, and the new targeted cancer therapies such as estimated glomerular filtration rate inhibitors can induce itch with and without a cutaneous eruption. A simple question, such as whether pruritus occurs in other family members, can indicate the possibility of scabies and prevent unnecessary investigation. Recent travel to endemic areas of parasitic infection and gastrointestinal complaints may be suggestive of parasitic infection. A positive review of systems, especially in relation to general health, such as weight loss, night sweats, and tremor, could point to a systemic cause.
Some pruritic states have specific clinical patterns. Despite severe pruritus, chronic urticaria does not usually show secondary skin lesions associated with scratching. Patients with cholestatic itch initially present with itch in an acral distribution in the palms and soles, whereas patients with other chronic types of itch rarely do so. Neuropathic itch in disease entities such as postherpetic neuralgia, brachioradial pruritus, and notalgia paresthetica involves itch in the relevant nerve distributions.
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