Prurigo Nodularis

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 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. 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.
• 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
• 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

Symptoms

• Usually affects a middle-aged or older patient, but may occur in children.⁵
• 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 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 general population).²

Signs

• Nodules/papules:
  • ≤2 cm in diameter
  • Discrete
  • Scaly
  • Symmetrical distribution
  • Firm
  • 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 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. 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)

It has a wide range of purported systemic precipitants including:

• Infective – Mycobacteria,⁶ Helicobacter pylori,⁷ Hepatitis C,⁸ HIV,³ Strongyloides stercoralis⁹
• Psychological/psychiatric conditions¹⁰
• Malignancies^11,12,13,14
• Renal failure

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.

• Pruritus screening bloods (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 and 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.
• 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.

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.¹⁵
• Opiate-receptor antagonists, such as naltrexone, have shown some efficacy in treating itch.¹⁶
• Systemic retinoids, such as acitretin, may shrink the nodules and reduce itching.
• 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.¹⁷
• Gabapentin has been used but may sedate patients.¹⁸

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.¹⁹ 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.²⁰
• Habit reversal therapy, originally developed to treat tics, has been used to break the 'itch-scratch' cycle.²¹
• 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.