Synonyms: PN, nodular prurigo, Hyde's disease, picker nodules, lichen corneus obtusus, nodular lichen simplex chronicus, nodular neurodermatitis circumscripta
This is a chronic inflammatory dermatosis of unknown aetiology. It causes a papulonodular eruption which is intensely itchy. Patients may be driven to distraction by the itch/scratch cycle that the disease induces, as may their doctors by their inability to treat the condition effectively.
The constant scratching leads to the development of discrete, excoriated, nodular, hyperpigmented/purpuric lesions with crusted or scaly surfaces. The scaling, thickening and hyperkeratosis of the skin, induced by scratching, is known as lichen simplex chronicus which may also present in a plaque-like form.
It predominantly affects the extensor aspects of the lower limbs but also commonly affects the arms and sometimes other areas of the body. Calcitonin gene-related peptide and substance P immunoreactive nerves are markedly increased in number and activity in the skin of prurigo nodularis sufferers, compared with normal skin. Whether this represents a causative aetiology or arises as a result of chronic scratching and skin irritation is not known. One study found hypoplasia of epidermal sensory nerves in the skin of prurigo nodularis sufferers even in areas where pruritus was not a problem.
- The condition appears to be relatively common, particularly among patients who have some of the associated/precipitating conditions but there are no surveys of its prevalence in the general population.
- It was originally described as a disease of middle-aged women, although currently there is not thought to be any convincing evidence of a female preponderance but it does appear to be more common in middle-aged people.
- In a modern, urban setting it appears to be the second most common dermatosis affecting those with HIV and relatively low CD4 counts. One study found that the development of prurigo nodularis in HIV patients was a sign of severe immunosuppression.
- It is thought that the prevalence of so-called neurotic excoriations, of which an unknown proportion of cases of prurigo nodularis might be a manifestation, is about 2% in dermatology clinics and 9% in those with an underlying cause for pruritus.
- It usually affects a middle-aged or older patient but may occur in children.
- The patient complains of long-standing pruritus that is a constant problem in the affected areas.
- There are specific sites that are identified as being itchy and on which pigmented nodular lesions later develop, usually symmetrically distributed.
- Nodules are usually of constant size and they do not resolve spontaneously.
- The number of nodules tends to increase over time.
- There may be a history of one of the associated conditions (see 'Associated diseases', below).
- Anxiety about the nature of the lesion and the itching is relatively common.
- Up to 80% of patients have a personal/family history of atopic dermatitis, asthma or hay fever (prevalence only ~25% in the general population).
- ≤2 cm in diameter.
- Symmetrical distribution.
- Hyperpigmented or sometimes purpuric.
- Usually on extensor surfaces of the legs/arms, and may occasionally affect the trunk.
- There may be a few lesions or up to several hundred in some cases.
- Patients may be observed to scratch repeatedly or rub the lesion during the consultation, often in preference to pointing them out when asked to indicate the problem.
There is a wide-ranging differential:
- Actinic keratosis.
- Amyloidosis, nodular localised cutaneous.
- Atypical fibroxanthoma.
- Chondrodermatitis nodularis helicis.
- Cutaneous horn.
- Cutaneous T-cell lymphoma.
- Dermatological manifestations of gastrointestinal disease.
- Dermatological manifestations of haematologic disease.
- Dermatological manifestations of renal disease.
- Hyperkeratosis lenticularis perstans (Flegel's disease).
- Insect bites.
- Knuckle pads.
- Lichen simplex chronicus.
- Lymphocytoma cutis.
- Lymphomatoid papulosis.
- Mastocytosis (urticaria pigmentosa).
- Milker's nodules.
- Molluscum contagiosum.
- Multicentric reticulohistiocytosis.
- Mycobacterium marinum infection of the skin (from cleaning out tropical fish tanks).
- Papulonecrotic tuberculids.
- Pretibial myxoedema.
- Squamous cell carcinoma.
It has a wide range of purported systemic precipitants including:
- Infective - mycobacteria, Helicobacter pylori, hepatitis C, HIV, Strongyloides stercoralis.
- Psychological/psychiatric conditions.
- Renal failure.
The role of these illnesses as precipitants or comorbidities is unclear. They may just be a range of conditions that induce a propensity to skin irritation and unmask a tendency to localised itchiness of the skin.
- Pruritus screening blood tests (such as FBC, CRP, iron studies, U&Es, LFTs, TFTs, serum calcium, glucose) may help to detect any underlying renal, hepatic, metabolic or infective associated illness.
- Biopsy of the lesions is recommended to exclude unusual or atypical presentations of other disease such as squamous cell carcinoma, mycobacterial infections, fungal infections and cutaneous lymphoma.
- Patch testing to look for evidence of a contact sensitivity precipitant may be carried out in a dermatology clinic.
Most treatments are somewhat disappointing in their lone efficacy and a trial of several treatments may be needed in individual patients; use of combination therapy may improve outcome in individual cases.
Local treatments include:
- Emollients - use frequently to cool and soothe itchy skin; menthol may be added to supplement this effect.
- Steroids are used to decrease inflammation and pruritus and to soften and smooth nodules, usually topically or under occlusive dressings but may be given intralesionally or orally. Response is often variable.
- Phenol and local anaesthetic creams have also been found to be helpful.
- Coal tar ointment is sometimes used as an alternative to steroids.
- Calcipotriol ointment is sometimes more effective than topical steroids.
- Capsaicin cream induces itching and burning and ultimately may stop itch. It requires repeated applications 4-6 times daily.
- Cryotherapy with liquid nitrogen can shrink the nodules and reduce their itch.
- Pulsed dye laser may reduce the vascularity of individual lesions.
- One study reported that hypnosis and acupuncture were beneficial.
Systemic therapies include:
- Antihistamines may help to control itch in some cases.
- Thalidomide has been shown to be quite effective in severe cases but carries a teratogenic and peripheral neuropathic risk.
- Opiate-receptor antagonists, such as naltrexone, have shown some efficacy in treating itch.
- Systemic retinoids, such as acitretin, may shrink the nodules and reduce itching.
- Psoralen combined with ultraviolet A (PUVA) treatment may help but carries the risks of prolonged UV exposure.
- There is anecdotal evidence of good response, in severe, refractory cases, to the immunomodulatory macrolide, roxithromycin, either alone, or combined with the anti-fibroblast agent, tranilast.
- The immunomodulators tacrolimus and pimecrolimus have been found to be beneficial in small studies of steroid-unresponsive patients and patients with thin skin.
- Gabapentin has been used to good effect. It can, however, cause sedation.
Psychological distress and depression in predisposed subjects may play a key role in inducing a pruritic sensation, leading to the scratching that perpetuates the condition (the 'itch-scratch cycle'). As with lichen simplex chronicus, it is thought that psychological factors play a role in causing and maintaining both conditions. One study found that anxiety and depression were common in prurigo nodularis patients. Approaches to address the psychodermatology include:
- Cognitive behavioural therapy (CBT) but there is little evidence of efficacy and patients must be open to a psychological model of their problem to have a good chance of responding.
- Habit reversal therapy, originally developed to treat tics, has been used to break the 'itch-scratch' cycle.
- Anxiolytic drugs may be helpful but there is a danger of dependence. Similarly, antidepressants such as amitriptyline or doxepin may be useful.
Consider referring the patient to a relevant specialist if you think the condition may be a manifestation of underlying systemic disease, particularly if HIV, malignancy, renal or liver disease is suspected.
Prurigo nodularis is a benign condition. However, it can cause severe functional impairment and morbidity due to poor control of the itching/scratching and psychological symptoms. Some lesions may become permanently pigmented or show scarring.
It is unusual for lesions to resolve spontaneously. They may lessen in severity with treatment but tend to persist over time. If the itch/scratch cycle can be completely broken then there is a chance of cure but this is not the norm.
Further reading & references
- Taefehnorooz H, Truchetet F, Barbaud A, et al; Efficacy of thalidomide in the treatment of prurigo nodularis. Acta Derm Venereol. 2011 May;91(3):344-5.
- Haas S, Capellino S, Phan NQ, et al; Low density of sympathetic nerve fibers relative to substance P-positive nerve J Dermatol Sci. 2010 Jun;58(3):193-7. Epub 2010 Apr 4.
- Schuhknecht B, Marziniak M, Wissel A, et al; Reduced intraepidermal nerve fibre density in lesional and nonlesional prurigo Br J Dermatol. 2011 Jul;165(1):85-91. doi: 10.1111/j.1365-2133.2011.10306.x.
- Hogan DJ et al; Prurigo Nodularis, Medscape, Jul 2010
- Zancanaro PC, McGirt LY, Mamelak AJ, et al; Cutaneous manifestations of HIV in the era of highly active antiretroviral therapy: an institutional urban clinic experience. J Am Acad Dermatol. 2006 Apr;54(4):581-8. Epub 2006 Feb 23.
- Magand F, Nacher M, Cazorla C, et al; Predictive values of prurigo nodularis and herpes zoster for HIV infection and Trans R Soc Trop Med Hyg. 2011 Jul;105(7):401-4. Epub 2011 May 28.
- Scheinfeld NS, Neurotic Excoriations, Medscape, Aug 2011
- Amer A, Fischer H; Prurigo nodularis in a 9-year-old girl. Clin Pediatr (Phila). 2009 Jan;48(1):93-5. Epub 2008 Jul 22.
- Saporito L, Florena AM, Colomba C, et al; Prurigo nodularis due to Mycobacterium tuberculosis. J Med Microbiol. 2009 Dec;58(Pt 12):1649-51. Epub 2009 Aug 6.
- Hernando-Harder AC, Booken N, Goerdt S, Singer MV, et al; Helicobacter pylori infection and dermatologic diseases. Eur J Dermatol. 2009 Sep-Oct;19(5):431-44. Epub 2009 Jun 15.
- Schwartz RA et al; Cutaneous Manifestations of Hepatitis C, Medscape, May 2011
- Schneider G, Hockmann J, Stander S, et al; Psychological factors in prurigo nodularis in comparison with psoriasis vulgaris: results of a case-control study. Br J Dermatol. 2006 Jan;154(1):61-6.
- Al-Waiz MM, Maluki AH; Squamous cell carcinoma complicating prurigo nodularis. Saudi Med J. 2000 Mar;21(3):300-1.
- Lin JT, Wang WH, Yen CC, et al; Prurigo nodularis as initial presentation of metastatic transitional cell carcinoma of the bladder. J Urol. 2002 Aug;168(2):631-2.
- Alfadley A et al; Treatment of prurigo nodularis with thalidomide: a case report and review of the literature, International Journal of Dermatology 2003, 42, 372 – 375.
- Lee MR, Shumack S; Prurigo nodularis: a review. Australas J Dermatol. 2005 Nov;46(4):211-18; quiz 219-20.
- Samuels N, Sagi E, Singer SR, et al; Hypnosis and acupuncture (hypnopuncture) for prurigo nodularis: a case report. Am J Clin Hypn. 2011 Apr;53(4):283-92.
- Doherty SD, Hsu S; A case series of 48 patients treated with thalidomide. J Drugs Dermatol. 2008 Aug;7(8):769-73.
- Prurigo nodularis, DermNet NZ; good illustrations
- Metze D, Reimann S, Beissert S, et al; Efficacy and safety of naltrexone, an oral opiate receptor antagonist, in the treatment of pruritus in internal and dermatological diseases. J Am Acad Dermatol. 1999 Oct;41(4):533-9.
- Eigelshoven,S Homey B; Prurigo nodularis, CME Dermatol 2009; 4(3): 140-155
- Gencoglan G, Inanir I, Gunduz K; Therapeutic hotline: Treatment of prurigo nodularis and lichen simplex chronicus Dermatol Ther. 2010 Mar-Apr;23(2):194-8.
- Dereli T, Karaca N, Inanir I, et al; Gabapentin for the treatment of recalcitrant chronic prurigo nodularis. Eur J Dermatol. 2008 Jan-Feb;18(1):85-6. Epub 2007 Dec 18.
- Dazzi C, Erma D, Piccinno R, et al; Psychological factors involved in prurigo nodularis: A pilot study. J Dermatolog Treat. 2011 Aug;22(4):211-4. Epub 2010 Jul 28.
- Shenefelt PD; Biofeedback, cognitive-behavioral methods, and hypnosis in dermatology: is it all in your mind? Dermatol Ther. 2003;16(2):114-22.
- Grillo M, Long R, Long D; Habit reversal training for the itch-scratch cycle associated with pruritic skin conditions. Dermatol Nurs. 2007 Jun;19(3):243-8.
Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.
|Original Author: Dr Sean Kavanagh, Dr Chloe Borton||Current Version: Dr Laurence Knott||Peer Reviewer: Prof Cathy Jackson|
|Last Checked: 28/09/2011||Document ID: 2675 Version: 23||© EMIS|