Prurigo Nodularis

Synonyms: PN, 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 papulo-nodular 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.¹ The constant scratching leads to the development of discrete, excoriated, nodular, hyper-pigmented/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. 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 commoner in middle-aged people.² It has a wide range of purported systemic precipitants including malignant conditions, renal impairment, infections and psychiatric conditions. The role of these illnesses as precipitants or co-morbidities 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. 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.¹ Whether this represents a causative aetiology or arises as a result of chronic scratching and skin irritation is not known.

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. In a modern, urban setting it appears to be the second commonest dermatosis affecting those with HIV and relatively low CD4 counts.³ 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.⁴

• Infective – Mycobacteria,⁵ Helicobacter pylori,⁶ Hepatitis C,⁷ HIV,³ Strongyloides stercoralis⁸
• Psychological/psychiatric conditions^9,10
• Malignancies^11,12,13,14
• Renal failure¹⁵

Symptoms

• Usually middle-aged or older patient
• Notice 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 usually of constant size and they do not resolve spontaneously
• Number of nodules tends to increase over time
• May be a history of one of the associated conditions (see above)
• 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 general population).²

Signs

• Nodules/papules up to 2cm in diameter that are discrete, scaly, symmetrically distributed, firm and hyperpigmented or sometimes purpuric
• Usually on extensor surfaces of legs/arms, may occasionally affect trunk
• May be a few lesions, up to several hundred in some cases
• Patients may be observed to repeatedly scratch 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. The conditions below are important to consider and exclude:

• Sarcoidosis
• Bullous pemphigoid
• Scabies
• Cutaneous amyloidosis
• Dermatitis artefacta
• Mycosis fungoides (cutaneous T-cell lymphoma)
• Actinic keratoses
• Atypical fibroxanthomata
• Insect bites
• Keratoacanthoma
• Molluscum contagiosum
• Mycobacterium marinum skin infection (from cleaning out tropical fish tanks)
• Squamous cell carcinoma
• Lymphomatoid papulosis
• Lymphocytoma cutis
• Pemphigoid nodularis
• Mastocytosis (urticaria pigmentosa)

• Screening bloods such as FBC, U&Es, LFTs – may help to detect any underlying renal, hepatic 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 multiple agents may improve outcome in individual cases.
• 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.
• Pruritus may respond to topical menthol, capsaicin, vitamin D₃ or anaesthetic preparations.
• Antihistamines may help some cases.
• Anxiolytic drugs may be helpful but there is a danger of dependence.
• It may be worth trying psychological therapies such as cognitive-behavioural therapy to break the itch-scratch cycle, 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.¹⁶
• Thalidomide has been shown to be quite effective but carries a teratogenic and peripheral neuropathic risk.
• Opiate-receptor antagonists have shown some efficacy in treating pruritus of various causes.¹⁷
• UV-light therapy with psoralens 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 combined with the anti-fibroblast agent tranilast.¹⁸
• Cryotherapy with liquid nitrogen can reduce pruritus and flatten lesions.
• Consider referring the patient to a relevant specialist if you think the condition may be a manifestation of underlying systemic disease, particularly HIV / malignancy / renal disease / liver disease.

Some lesions may become permanently pigmented or show scarring.

It is unusual for lesions to spontaneously resolve. They may lessen in severity with treatment but tend to persist. If the itch/scratch cycle can be completely broken then there is a chance of cure but this is not the norm.