Prurigo nodularis

Synonyms: nodular prurigo, Hyde's disease, picker nodules, lichen corneus obtusus, nodular lichen simplex chronicus, nodular neurodermatitis circumscripta

What is prurigo nodularis?

Prurigo nodularis is a chronic, recalcitrant inflammatory skin condition characterised by pruritic nodules. The exact cause of the condition is unknown, although immune and neural dysregulation are indicated in driving the itch-scratch cycle¹ .

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.

Prurigo nodularis predominantly affects the extensor aspects of the lower limbs but also commonly affects the arms and sometimes other areas of the body. There are increased dermal levels of neuropeptides such as substance P, calcitonin gene-related peptide and nerve growth factor, as well as an excess of eosinophils and mast cells² .

People with prurigo nodularis also have a reduced intraepidermal nerve fibre density. 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 those with prurigo nodularis, even in areas where pruritus was not a problem³ .

Prurigo nodularis epidemiology

• Prurigo nodularis appears to be relatively common, particularly among patients who have some of the associated/precipitating conditions; however, there are no surveys of its prevalence in the general population.

• It is more common in middle-aged women⁴ .

• Prurigo nodularis was common in HIV-positive patients before the advent of antiretroviral therapy (ART) but is now.relatively uncommon in treated patients⁵ . However, it is still prevalent where access to ART is limited. One study found that the development of prurigo nodularis in HIV patients was a sign of severe immunosuppression⁶ .

Presentation

Prurigo nodularis

By Michael Katotomichelakis, Dimitrios G Balatsouras, Konstantinos Bassioukas, Nikolaos Kontogiannis, Konstantinos Simopoulos, Vassilios Danielides, CC BY 2.0, via Wikimedia Commons

Prurigo nodularis symptoms

• It usually affects a middle-aged or older patient but may occur in children⁷ .

• 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 (compared to 25% of the general population)⁸ .

Signs

• Nodules/papules:
  

  • ≤2 cm in diameter.

  • Discrete.

  • Scaly.

  • Symmetrical distribution.

  • Firm.

  • 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.

Differential diagnosis^{9 10}

There is a wide-ranging differential:

• Actinic keratosis.

• Amyloidosis, nodular localised cutaneous.

• Atypical fibroxanthoma.

• Chondrodermatitis nodularis helicis.

• Cutaneous horn.

• Cutaneous T-cell lymphoma.

• Dermatofibroma.

• Dermatological manifestations of gastrointestinal disease.

• Dermatological manifestations of haematological disease.

• Dermatological manifestations of renal disease.

• Hyperkeratosis lenticularis perstans (Flegel's disease).

• Insect bites.

• Keratoacanthoma.

• 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.

• Pilomatrixoma.

• Pretibial myxoedema.

• Sarcoidosis.

• Squamous cell carcinoma.

• Xanthomas.

Associated diseases

Prurigo nodularis has a wide range of purported systemic precipitants, including:

• Infective:

  • Mycobacteria¹¹

  • Helicobacter pylori¹² .

  • Hepatitis C¹³ .

  • HIV⁶ .

• Psychological/psychiatric conditions¹⁴ .

• Malignancies^{15 16 17} .

• Acute kidney injury.

The role of these illnesses as precipitants or comorbidities is unclear. They may just be a range of conditions which induce a propensity to skin irritation and unmask a tendency to localised itchiness of the skin.

Investigations⁸

• 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.

• Dermoscopy may be helpful in differentiating various nodular pruritic conditions¹⁸ .

• Direct immunofluorescence looking for antibody deposition in the skin may be necessary to differentiate from bullous pemphigoid if blisters develop.

Prurigo nodularis treatment and management^{8 199}

Treatment typically relies on the use of topical or intralesional steroids. More severe or treatment-resistant cases often require phototherapy or systemic immunosuppressives. Thalidomide and lenalidomide can both be used in severe cases, but toxicity makes them less favourable. Opioid receptor antagonists and neurokinin-1 receptor antagonists represent two potential therapeutic agents which may effectively treat prurigo nodularis with a lower toxicity profile than thalidomide or lenalidomide²⁰ .

Local treatments
These 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.

• Intranodular steroid injections are sometimes used.

• 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 beneficial²¹ .

Systemic therapies²²
These include:

• Antihistamines may help to control itch in some cases.

• The response to systemic corticosteroids is very unpredictable.

• Ciclosporin, methotrexate and azathioprine have been found to be effective in some cases.

• Thalidomide has been shown to be quite effective in severe cases but carries a teratogenic and peripheral neuropathic risk²³ .

• 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, tranilast²⁴ .

• 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 patients¹⁴ . Approaches to address the psychodermatology include:

• Cognitive behavioural therapy (CBT). However, there is little evidence of efficacy and patients must be open to a psychological model of their problem to have a good chance of responding²⁵ .

• Habit reversal therapy, originally developed to treat tics, has been used to break the 'itch/scratch' cycle²⁶ .

• Anxiolytic drugs may be helpful but there is a danger of dependence. Similarly, antidepressants such as amitriptyline or doxepin may be useful.

• One study reported control of pruritus with oral ketotifen and topical antibiotics²⁷ .

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. Referral should also be considered if all therapeutic options available in primary care have been exhausted⁹ .

Complications

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.

Prognosis

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.