Prurigo Nodularis

Updated: Aug 02, 2018
  • Author: Amarateedha H Prak LeCourt, MD; Chief Editor: William D James, MD  more...
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Overview

Background

In 1909, Hyde and Montgomery [1] first described prurigo nodularis as pruritic nodules on the extensor surfaces of the lower extremities in middle-aged women. Prurigo nodularis can be a bothersome-to-debilitating disease, usually seen as multiple, intensely pruritic, excoriated nodules erupting on the extensor surfaces of the limbs secondary to itching or rubbing. In current practice, prurigo nodularis is still a condition of unknown etiology. Many conditions have been reported to induce prurigo nodularis, from internal malignancy to renal failure to psychiatric conditions.

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Pathophysiology

Chronic mechanical trauma to the skin causes thickening of the skin proportionate to the trauma. Repetitive rubbing, scratching, and touching (induced by a foreign body or self-induced) results in plaques or nodular lichenification and hyperkeratosis. Pigmentary changes often result from such repetitive trauma to the skin.

With prurigo nodularis, a person feels intense pruritus at discrete points and cannot control the urge to rub or scratch these points on the body. Any abnormality or explanation for the pruritus is unknown; scratching by the individuals who are affected is obvious. The results are discrete, nodular, hyperpigmented/purpuric lesions with surfaces that are scaly, excoriated, and possibly crusted.

Immunohistochemical studies demonstrate increased numbers of dermal nerve fibers in prurigo nodularis. The sensation of pruritus is transmitted mainly by thin, unmyelinated epidermal nerves. Lesional and uninvolved prurigo nodularis skin biopsies showed significantly decreased intraepidermal nerve fiber density, suggesting the presence of a subclinical small fiber neuropathy in prurigo nodularis. [2] However, in a 2017 study, it was suggested that scratching may be the cause of the reduced intradermal nerve fiber density and not an underlying neuropathy. [3] It was demonstrated that lesions that had healed had a full reconstitution of intradermal nerve fiber density, which supports the theory that the disturbed epidermal anatomy is secondary to the mechanical trauma rather than a functional neuropathy. [3] Another study indicated that Th2 cytokines related to STAT6 activation together with some unknown stimuli that activate STAT3 play a principal role in the pathogenesis of prurigo nodularis. [4]

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Etiology

The cause of prurigo nodularis is still unknown. Many associated conditions are known, but their roles as coexisting or preexisting conditions have not been established in causing prurigo nodularis. Notable changes in papules and nodules are increased in certain inflammatory cell types, inflammatory products, and neural hyperplasia.

Mast cells and neutrophils are seen in higher-than-normal levels in prurigo nodularis; however, their degranulation products are not increased. Eosinophils are not seen in higher numbers; however, the protein granule products (ie, major basic protein, eosinophil cationic protein, eosinophil-derived neurotoxin) are seen in significantly higher levels.

Papillary dermal nerves and Merkel cells are sensory nerves found in the dermis and the epidermis, respectively. [5] They are both found in increased numbers in prurigo nodularis. These are neural receptors that sense touch, temperature, pain, and itch. These increases in sensory nerves are not seen in lichen simplex chronicus, another pruritic disease that causes epidermal hyperplasia but in a plaquelike morphology.

Calcitonin gene–related peptide and substance P immunoreactive nerves are markedly increased in prurigo nodularis skin compared with normal skin. [6] These neuropeptides may mediate the cutaneous neurogenic inflammation and pruritus in prurigo nodularis. In addition, the capsaicin-binding nonselective cation channel known as vanilloid receptor subtype 1 has highly increased expression in epidermal keratinocytes and nerve fibers in prurigo nodularis lesions, but these can be normalized with capsaicin application.

Hepatitis C, mycobacteria, [7, 8, 9] Helicobacter pylori, Strongyloides stercoralis, [10] and HIV have been reported as infectious etiologies of prurigo nodularis or as associated with prurigo nodularis in case reports or from single-center studies.

Interleukin 31, a T-cell–derived cytokine that causes severe pruritus and dermatitis in transgenic mice, is elevated in individuals with prurigo nodularis. [11] Interleukin 31 expression in atopic individuals is also rapidly induced by staphylococcal superantigen; however, the link between these findings has not been extensively researched.

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Epidemiology

Race

No racial disparity is known for prurigo nodularis.

Sex

Women were formerly believed to have a disproportionate amount of prurigo nodularis compared to men; however, no documented difference exists in frequency between the sexes.

Age

Prurigo nodularis can occur at any age, but it most often occurs in middle-aged and older persons.

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Prognosis

Prurigo nodularis is benign and does not increase mortality; however, severe morbidity can occur in untreated and even in some treated persons who are affected. Pruritus and the extent of body surface area involved become so great for some patients that they no longer feel functional for work or other everyday activities.

Some conditions associated with prurigo nodularis may cause mortality. Prurigo nodularis has been documented to be much more common in immunocompromised and HIV populations. The positive predictive value (PPV) for HIV positivity was 36% for prurigo nodularis in a study from French Guiana. The PPV for having a CD4 lymphocyte count of less than 200/mcL was 72% for prurigo nodularis. Prurigo nodularis was thus predictive of advanced immunosuppression, and, in the absence of facilities to perform a CD4 count, this study suggests that HIV antiretrovirals should be initiated for patients with prurigo nodularis in third world countries. [12]

Some cases of prurigo nodularis are associated with internal malignancy. Hodgkin disease (lymphoma) may present with pruritus and lichenified nodules. [13] Prurigo nodularis may be the first manifestation of chronic autoimmune cholestatic hepatitis [14] and may be seen with severely decreased kidney function and uremic pruritus.

The prognosis for spontaneous remission of prurigo nodularis is not good. Once prurigo nodularis lesions occur, complete resolution of lesions is uncommon. Most lesions remain present in some form even after long-term treatment. At this time, treating more than just the most symptomatic lesions is difficult. Considerable time is usually required to slow or stop the itch/scratch cycle so that the lesions resolve.

Ultimately, a strong therapeutic alliance is the best outcome predictor because the course of the disease is long, with waxing and waning symptoms, making the patient prone to being subjected to excessive diagnostic procedures and to seek alternative therapies.

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