Chapter 15. Nummular Eczema, Lichen Simplex Chronicus, and Prurigo Nodularis

Epidemiology

Nummular eczema is predominantly a disease of adulthood. Men are more frequently affected than women. The peak incidence in both males and females is around 50–65 years of age. There is a second peak in women around 15–25 years of age. Nummular eczema is rare in infancy and childhood. The peak age of onset in childhood is 5 years.1

Etiology and Pathogenesis

The pathogenesis of nummular eczema is still unknown. The vast majority of patients with nummular eczema do not have a personal or family history of atopy,2,3 although nummular plaques may be seen in atopic eczema. Numerous factors have been implicated as causal. The state of hydration of the skin in elderly patients has been shown to be decreased.4 The role of infection previously received much attention in the literature. An internal focus of infection, including teeth, upper respiratory tract, and lower respiratory tract, was found in 68% of patients in one study.5 Eleven of thirteen patients without a history of atopic eczema improved after odontogenic infections were treated.6 A role for environmental allergens, such as the house dust mite and Candida albicans has also been touted.4 Nummular eczema has been reported during therapy with isotretinoin and gold.7,8 Generalized nummular eczema is seen in patients with hepatitis C undergoing combination therapy with interferon α-2b and ribavirin.9,10 Mercury amalgam was implicated as a cause in two patients.11

Clinical Findings

Well-demarcated coin-shaped plaques form from coalescing papules and papulovesicles. Pinpoint oozing and crusting eventuate, and are distinctive (Figs. 15-1 and 15-2). Crust may however cover the entire surface (Fig. 15-3). Plaques range from 1 to 3 cm in size. The surrounding skin is generally normal but may be xerotic. Pruritus varies from minimal to severe. Central resolution may occur, leading to annular forms. Chronic plaques are dry, scaly, and lichenified. The classic distribution of lesions is the extensor aspects of the extremities. In women, the upper extremities, including the dorsal aspects of the hands, are more frequently affected than the lower extremities.2 Exudative discoid and lichenoid dermatitis of Sulzberger-Garbe may represent a variant of nummular dermatitis.12

Laboratory Tests

Patch testing may be useful in chronic recalcitrant cases to rule out a superimposed contact dermatitis. In a series from India, just under half of 50 patients were patch-test positive to colophony, nitrofurazone, neomycin sulfate, and nickel sulfate.13 Serum IgE levels are normal.

Special Tests

Histopathologic changes are reflective of the stage at which the biopsy is performed. Acutely, there is spongiosis, with or without spongiotic microvesicles. In subacute plaques, there is parakeratosis, scale-crust, epidermal hyperplasia, and spongiosis of the epidermis (Fig. 15-4). There is a mixed cell infiltrate in the dermis. Chronic lesions may resemble lichen simplex chronicus microscopically.

Differential Diagnosis

See Box 15-1.

Complications

Nummular eczema may be complicated by secondary bacterial infection.

Prognosis/Clinical Course

The course is usually chronic. Recurrence at prior sites of involvement is a feature of the disease.5

Treatment

Topical steroids in the mid- to high-potency range are the mainstay of treatment. The calcineurin inhibitors, tacrolimus and pimecrolimus, and tar preparations are also effective. Emollients can be added adjunctively if there is accompanying xerosis. Oral antihistamines are useful if pruritus is severe. Oral antibiotics are indicated when secondary infection is present. For widespread involvement, phototherapy with broad- or narrow-band ultraviolet B may be beneficial.

Epidemiology

Lichen simplex chronicus affects adults, predominantly from ages 30 to 50. Females are affected more commonly than males. Prurigo nodularis may occur at any age, but most patients are between 20 and 60 years.14 Men and women are equally affected. Patients with coexistent atopic dermatitis have been found to have any earlier age of onset (mean: 19 years) as compared to the nonatopic group (mean: 48 years).15

Etiology and Pathogenesis

Lichen simplex chronicus is induced by rubbing and scratching secondary to itch. The prurigo nodule is induced by picking and scratching most commonly, but not always, in response to itch. Various factors incite itch in both disorders and not all are well understood. A variable association between lichen simplex chronicus and atopic disorders has been reported, ranging from around 26% to 75%.16,17 Similarly, a subset of patients with prurigo nodularis has coexistent atopic eczema. Here, prurigo nodules occur in concert with subacute prurigo, lichenification, and xerosis. “Besnier prurigo” refers to the pruriginous nodules seen in atopic dermatitis. In the nonatopic nodular prurigo group, systemic causes of pruritus, including renal insufficiency, hyper- or hypothyroidism, liver failure, HIV disease, parasitic infection, or an underlying malignancy must be excluded. Hepatitis B and C have been reported as associations without liver failure.18 Prurigo nodularis has also been reported to occur in the setting of celiac disease in the presence or absence of dermatitis herpetiformis.19,20 The relationship between lichen simplex chronicus and radiculopathy has been preliminarily investigated.21 Further studies are needed to clarify whether an association exists.

Environmental factors have been implicated in inducing itch, such as heat, sweat, and irritation associated with anogenital lichen simplex chronicus.17 The presence of emotional or psychological factors in patients with prurigo nodularis and lichen simplex chronicus has been alluded to in the literature. One study of prurigo nodularis patients found that around half of 46 patients had a history of depression, anxiety, or other treatable psychological disorders.22 Lichen simplex chronicus patients also had higher depression scores in one study.23 Whether these emotional factors are secondary to the primary dermatologic disease or whether they are primary and causative, altering perception of itch, is unclear. It has been postulated that neurotransmitters that affect mood, such as dopamine, serotonin, or opioid peptides modulate perception of itch via descending spinal pathways.14 Obsessive-compulsive disorder (OCD) has also been associated with picking in these disorders.24

At a microscopic level, increased numbers of Merkel cells are also seen adjacent to the dermal nerve fibers and mast cells in prurigo nodularis. It is thought that this complex may mediate the abnormally heightened perception of touch and itch in these patients. Nerve growth factor (NGF) is overexpressed in prurigo nodularis lesions and it has been implicated in the pathogenesis of the characteristic cutaneous neural hyperplasia seen.25 NGF is produced and released by mast cells, which are increased in number and size on histologic sections. It upregulates the expression of neuropeptides, such as calcitonin gene-related peptide and substance P. These are thought to mediate inflammation and itch.17

Clinical Findings

History

Severe itching is the hallmark of lichen simplex chronicus. Itching may be paroxysmal, continuous, or sporadic. Rubbing and scratching may be conscious and to the point of replacing the sensation of itch with pain, or may be unconscious, occurring during sleep. Itch severity is worse with sweating, heat, or irritation from clothing. Itching is also worse in times of psychological distress.18

Cutaneous Lesions

In lichen simplex chronicus, repeated rubbing and scratching gives rise to a lichenified, scaly plaque with excoriations. Hyper- and hypopigmentation are seen with chronicity. Usually, only one plaque is present; however, more than one site may be involved. The most common sites of involvement are the scalp, the nape of the neck (especially in women), the ankles, the extensor aspects of the extremities, and the anogenital region.26 The labia majora in women and the scrotum in men (Fig. 15-5) are the most common sites of genital involvement.16 The upper inner thighs may also be affected.

Prurigo nodules vary in size from 0.5 to 3 cm and are firm to hard on palpation. The surface may be hyperkeratotic or crateriform. There is often overlying excoriation. Pruritus is usually severe. Limbs are affected in most cases, especially the extensor aspects (Fig. 15-6). The abdomen and sacrum were the next most common sites of involvement in one study.22 Face and palms are rarely involved; however, nodules may occur on any site that can be reached by the patient. Lesions may vary in number from few to more than one hundred. Nodules resolve with postinflammatory hyper- or hypopigmentation with or without scarring.

Related Physical Findings

In patients with atopic eczema, the intervening skin is often lichenified and xerotic. In nonatopic patients, cutaneous signs of underlying systemic disease or lymphadenopathy, signifying lymphoma, may be present.

Laboratory Tests

In patients with prurigo nodularis in whom an underlying systemic cause of pruritus is suspected, a complete blood count with differential count, renal, liver, and thyroid function tests may be ordered. A chest X-ray may be obtained to screen for lymphoma. HIV testing may also be indicated. The need for a more extensive evaluation may be individualized based on patient history and results of the aforementioned tests.

Special Tests

On histopathologic sections, lichen simplex chronicus shows varying degrees of hyperkeratosis with para- and orthokeratosis, hypergranulosis, and psoriasiform epidermal hyperplasia. The papillary dermis shows thickening of collagen with coarse collagen bundles and vertical streaks. There is a variable inflammatory infiltrate around the superficial vascular plexus with lymphocytes, histiocytes, and eosinophils. A biopsy may also reveal a primary pruritic disorder that has led to secondary lichenification, such as psoriasis.

The epidermal findings in prurigo nodularis are similar to lichen simplex chronicus. The lesion is more papular with bulbous epidermal hyperplasia. Papillary dermal changes also resemble lichen simplex chronicus. There may be cutaneous neural hypertrophy with thickened nerve bundles and an increase in nerve fibers by S-100 staining. This finding was seen in the minority of cases in a recent study.27

Differential Diagnosis

See Boxes 15-2 and 15-3.

Complications

Sleep studies have shown that disturbances in the sleep cycle in lichen simplex chronicus are present. Non-REM sleep is disturbed and patients have an increased arousal index (brief awakenings from sleep) caused by scratching.28

Prognosis/Clinical Course

Both diseases run a chronic course with persistence or recurrence of lesions. Exacerbations occur in response to emotional stress.

Treatment

Treatment is aimed at interrupting the itch–scratch cycle. Both components should be addressed. Systemic causes of itch should be identified and addressed. In both conditions, first-line measures to control itch include potent topical steroids as well as nonsteroidal antipruritic preparations such as menthol, phenol, or pramoxine. Emollients are an important adjunct. Intralesional steroids, such as triamcinolone acetonide, given in varying concentrations according to the thickness of the plaque or nodule are beneficial. Topical tacrolimus has been successfully employed as a steroid-sparing agent. Sedating antihistamines, such as hydroxyzine, or tricyclic antidepressants, such as doxepin, may be used to abolish nighttime itch in both conditions. Selective serotonin reuptake inhibitors (SSRIs) have been recommended for relief of daytime pruritus or in patients with OCD.17

Capsaicin, calcipotriene, and cryotherapy, with or without intralesional steroid injections, have all been successfully used in prurigo nodularis. Both broad- and narrow-band ultraviolet B, as well as topical or oral PUVA show efficacy and are indicated in widespread cases. The 308 nm excimer monochromatic light, UVA1 phototherapy, and naltrexone were all effective in small series.29–31 Thalidomide and cyclosporine have also been shown to be beneficial.

The importance of avoiding scratching should be addressed with the patient. Nails should be kept short and occlusive measures, such as plastic films, topical steroid tape, or Unna boots in widespread cases may be needed.