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Prurigo nodularis

2005

A skin disease characterised by pruritic nodules which usually appear on the arms or legs.

A chronic dermatologic condition with itchy, excoriated nodules on the extensive surfaces of the arms legs and trunk.

Patients often have multiple excoriated lesions caused by scratching.

Characterized by hybrid keratotic, crusted or excoriated, light-red to bright-red nodules.

Additional names: Hyde prurigo nodularis, Picker’s nodules, atypical nodular form of neurodermatitis circumscripta, and lichen corneus obtusus.

Clinically the nodules are discrete, generally symmetric, hyperpigmented or purpuric, and firm.

Nodules are greater than 0.5 cm in both width and depth

Lesions can appear on any part of the body, but generally begin on the arms and legs.

Skin lesions may range in number from a few to hundreds and they can range from a few millimeters to 2-3 cm in diameter.

In most cases it is a generalized process, with symmetric distribution of the lesions on the extensor surfaces of the arms and legs and on the trunk.

Excoriated lesions may become flat, umbilicated, or crusted.

Typically a nodule forms before any itching begins.

Nodules are extremely pruritic and are alleviated only by steroids.

Cause is unknown.

The sensation of the neural transmission of itch involves cutaneous nerve fibers in the skin to the dorsal root ganglion, spinal cord and brain.
The itch cascade is bidirectional, with its recognition in the brain producing a response of stimulating motor neurons to prompt scratching through complex mechanisms.
The itch-scratch biologic cycle is thought to be secondary to neuroimmune dysregulation.
In prurigo nodularis the cutaneous nerve architecture is disrupted and skin lesions show thickening, and increased numbers of dermal nerves.

T cells, eosinophils, mast cells are inflammatory cells that are increased with PN and they secrete neurotrophins that promote neurogenic inflammation.

The disorder is most common in middle age or later, and can be associated with chronic kidney disease, type two diabetes, and human immunodeficiency virus infection.
Its hallmark is unrelenting itching, greater in intensity and frequency than with other chronic pruritic skin diseases.
Patients experience markedly impaired quality-of-life, sleep deprivation, social isolation, anxiety, and depression.

Considered a form of neuronal sensitization of itch processing neurons and the development of itch-scratch cycle.

Skin and neuronal plasticity play a role, with study showing nerve fiber alterations in the epidermis and dermis and the presence of inflammatory cells in the dermis.

Up regulation of interleukin-31 messenger RNA has been reported to be 50 times as high in these patients lesions as in biopsy samples from healthy individuals.

Has some predilection for elderly individuals and for patients with dark skin, including persons of African ancestry.

Interleukin-31 receptor is involved in the pathogenesis of prurigo nodularis.

Linked to Becker’s nevus, linear IgA disease, an autoimmune condition, liver disease and T cells.

Systemic pruritus has been linked to cholestasis, thyroid disease, polycythaemia rubra vera, uraemia, Hodgkins disease, HIV and other immunodeficiency diseases.

Internal malignancies, liver failure, renal failure, and psychiatric illnesses may induce PN.

With repeated scratching, picking, or rubbing of the nodules, permanent changes to the skin such as lichenification, hyperkeratosis, hyperpigmentation, and skin thickening may occur.

Such unhealed, and excoriated lesions are often scaly, crusted or scabbed, and are difficult to heal.

Patients usually seek treatment during middle-age, although it can occur at any age.

Patients with PN often have a history of chronic severe pruritus and medically unrelated conditions such as liver orb kidney dysfunction.

Secondary screen infections are common.

Patients frequently have a personal or family history of atopic dermatitis, or other autoimmune disorders.

Diagnosis is based on visual examination and the presence of itching.

A skin biopsy is often performed to exclude other skin diagnoses.

Histological analysis frequently shows icreased eosinophils.

37% of patients have anxiety,29% depression, and suicidal ideation has been reported in 19% of patients.

It is a difficult lesion to treat.

It is typically refractory to treatment and may be associated with diabetes, chronic kidney disease, and HIV.

The intensity of pruritus is to be among the highest of several types of chronic pruritic skin disease.

Treatments include: steroids, cryosurgery, UVB light, vitamins and antibiotics if infection is present.

Topical glucocorticoids and anti-histamines are ineffective.

Prurigo nodularis is very hard to treat, but current therapies include steroids, vitamins, cryosurgery, thalidomide and UVB light, and antibiotics if infection is present.

Nemolizumab is a monoclonal antibody targeting the interleukin-31 receptor, which is involved in the pathogenesis of prurigo nodularis.

Nemolizumab Use resulting in a greater reduction in pruritus and severity of skin lesions than placebo but is associated with adverse events of abdominal pain,diarrhea and musculoskeletal symptoms.

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