chronic prurigo etiology and therapy

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Chronic Prurigo Etiology and Therapy

JOANNA WALLENGREN

University Hospital Lund Sweden

The term prurigo, originating from the Latin

word pruire, to itch, was first used by

Ferdinand von Hebra in the mid-19th century

to characterize intensely itchy papules and

nodules that occur mainly on the arms and

legs. At that time, prurigo was one of the most

frequent forms of skin disease in Eu rope, being

closely associated with the stings of parasites,

such as fleas and mites, that commonly

afflicted humans. The genuine chronic form of

prurigo is named prurigo nodularis of Hyde

after the man who coined the term in 1909 [1].

Th is review will deal with this and other forms

of chronic prurigo secondary to an underlying

systemic disease or external provoking factors.

In addition, it will focus on the preponderance

of prurigo in certain ethnic groups.

The diagnosis of prurigo is a clinical one

and histopathology confirms what is seen by

the naked eye; hyperkeratosis, acanthosis, and

occasional epidermal necrosis due to picking.

Prurigo Nodularis of Hyde

Prurigo nodularis can occur at any age,

although mainly from 20-60 years, with both

sexes equally affected. The lesions are

hemispherical, often irregular nodes with a

horny, rhagadiform, or crateriform depressed

surface. They may be as much as several

centimeters in diameter and are mainly located

on extensor surfaces of the extremities,

although the trunk, face, and even palms can

also be affected [1]. New no dule s gen erally

develop from time to time, and existing

nodules can remain pruritic indefinitely,

although some regress spontaneously leaving

about whether the prurigo nodularis lesion

appears first and produces an urge to scratch

or whether its appearance is bought about as

a consequence of scratching [1].

According to Hebra, the prurigo papule

appea rs first. In 1899, John ston w rote in the

ournal of utaneous Diseases that the number

of hypertrophic nerve fibers is increased in

pru rigo lesions [2]. Th ese nerve fibers show

immunoreactvity for sensory neuropeptides ,

such as calcitonin gene-related peptide, and

substance P which act as itch transmitters in

both the per ipheral and central nervous

systems [3].This finding supports the theory

of itch being elicited from the prurigo lesion.

The central neuronal pathways involved in

itch transmission terminate in both the

somatosensory cortex and the motor areas that

cause scratching

[4].

Tissue inju ry at different

signal transmission levels or any alterations in

neurotransm itter concentrations (such as in as

in various psychogenic disorders) may

contribute to both itch perception and the

desire to scratch [4]. Simp le treat m ent s,

including occlusion with elastic bandages for

4 weeks, will improve the clinical picture of

prurigo with no enlarged nerve fibers or

neurinoma-like structures remaining visible.

Such an involution of prurigo nodules would

favor the theory that scratching is the

triggering factor of prurigo.

As shown in a clinical study of

6

patients

with chronic prurig o, 72 of patien ts felt

that psychosocial problems were of relevance

to the ir skin disease and 50 were found to

be suffering from depression, anxiety, or


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Joanna Wallengren

neurotransmitters such as dopamine,

serotonin, or opioid peptides modulate

sensory perception. Of the patients in this

study, 65-80 were atopic , which would

explain the original appearance of the first

papulae. In addition, potential metabolic

causes of pruritus, such as anemia, hepatic

dysfunction, uremia, and myxedema were

present in 50 of the patien ts [5].

Prurigo in ssociation

with Systemic Disease

Several internal diseases associated with

itching may involve the formation prurigo

nodularis-like lesions.

nternal

iseases

Itch is a common symptom in patients with

chronic renal failure receiving maintenance

hemodialysis. Perforating folliculitis with

superimposed prurigo nodularis in these

patients was first described in 1982 [6].

Interestingly, in one patient, who had been

completely unresponsive to various treat-

ments, the skin lesions cleared up rapidly

1 week after cessation of hemodialysis and

renal allograft transplantation

[6].

Acquired

reactive perforating collagenosis, a rare

disease usually associated with diabetes

mellitus or renal failure, may involve chronic

prurigo [7]. In addition, prurigo-like lesions

are associated with various other collagen

diseases such as discoid lupus erythematosus,

systemic scleroderma, and adult-onset Still

disease [8]. Furthermore, pruritus is

experienced by a large proportion of patients

with cholestasis. Recent evidence suggests

that this is precipitated by an altered form of

neurotransmission in the brain. [9J

Matabsorption

The association between prurigo and

malabsorption was first observed by Wells in

1962, who described a patient with gluten

enteropathy [lOJ. Since then, seven

additional patients with celiac disease and

therapy-resistant prurigo have been

the intestinal symptoms improved and the

typical clinical prurigo nodules disappeared,

or improved. As dermatitis herpetiformis is

commonly associated with gluten entero-

pathy it would appear that this may be a

significant factor in the onset of prurigo in

patients with gluten enteropathy. [11]

Itching and prurigo are also clinical

features that are associated with anorexia

nervosa [12]. The symptoms disappear with

the restoration of weight in these patients.

Malignancy

Prurigo has been associated with T cell

lymphoma and visceral neoplasia in the

esophagus, ventricles, rectum, liver, and

bile duct [13,14]. Prurigo of the lymphoma

may precede symptoms of malignancy. Its

occurence can also be a warning signal for

malignant transformation in patients with

tumors previously diagnosed as benign [14].

nves tigation of an

ssociated Disease

Screening is limited to a complete blood

cell count as a marker of hematological

disease and liver enzymes as markers of

hepatic and renal disease. In case of any

differing pathologies a specific investigation

is normally recommended. In addition,

gastrointestinal symptoms are usually

investigated by specific examination.

In reluctant, longstanding cases of

chronic prurigo a biopsy is advised to ensure

that a squamous cell carcinoma (that

may occasionally complicate longstanding

chronic prurigo nodules) is not overlooked.

Furthermore, biopsy with immunofluore-

scence may be useful to exclude the diagnosis

of pemphigoid nodularis.

Prurigo in ssociation

with External Factors

nfections and

Parasitoses

The relationship between prurigo and imm uno-

suppression is illustrated by the fact that

prurigo is diagnosed in approximately 6 of


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Chronic Prurigo: Etiology and Therapy

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thus are more likely to experience exaggerated

imm unological phenomena [16]. The pru ri-

ginous lesions may present such phenomena as

a result of insect stings or chronic pru rigo [15].

This is normally termed prurigo stroph ulus (or

papular urticaria); an acute form of prurigo

caused by hypersensitivity to insect bites in

genetically predisposed individuals, which can

be provoked by the bites of fleas, mosquitos,

ticks,

or dog parasites.

The increased incidence of zoonotic ,

parasitic, and helmetic infections in large

parts of the world, such as in Africa, can be a

major cause of morbidity and mortality and

an increase in the incidence of prur igo

strop hulu s [17]. In additio n, prurigo has also

been found in association with Lyme

borreliosis, mycobacteria,

elicobacter

pylori

and cutaneous toxoplasmosis [18].

Light Induced Eruptions

Hutchinson summer prur igo, descr ibed in

1878, occurs in children and young adults.

This erythematous papular eruption affects

areas exposed to light, most commonly the

face [19]. It is rarely seen in Eu rop e and

appears to be identical to the actinic prurigo

found predominantly in native North- and

South-American Indians [20].

Actinic prurigo is a chronic photoder-

matit is character ized by intense prur itus ,

prurigo-like papules on light exposed areas,

cheilitis, conjunctivitis, scars, and alopecia of

the eyebrows [20]. Generally, it appears at an

early age, usually according to a family history

and predominantly in females. In addition, it is

more frequently observed at high altitudes

(>2000 m), with outdoor occupations, and with

a predominance of human LA protein-DR4.

Sutton summer prurigo of the elbows

appears as a papular eruption, usually limited

to the elbows, although it may also affect the

knees, hands, or chest [21]. It is related to

atopic eczema and frequently affects children

during the first few weeks of spring or summer

and tends to recur for several years.

etanercept has been found to induce acute

prur igo, carbamazepine subacute prur igo,

and etretinate to induce nodular prur igo-

like reactions.

Other orms of Prurigo

Prurigo pigmentosa, first reported by Naga-

shima in 1971, is a distinct clinical entity that

is highly prevalent in Japan, where >200 cases

have been reported, predominantly in women

[22].

The disorder is less common in non-

Japanese patients, although there have been

cases reported in Turkey and Sicily. Lesions of

this form of prurigo are typically pruritic red

papules followed by reticular hyperpigmented

mottling. Characteristically, this occurs on the

back, neck, and chest. Histologically, the

lesions are lichenoid in character and display a

certain pigmentary incontinence; onset usually

occurs in the spring and summer months. An

association between prurigo pigmentosa and

both insulin-dependent diabetes and anorexia

nervosa has been reported in Japan.

Papular eruption in black men was

reported in 1980 by Rosen and Algra [23].

They described seven young black patients

with persistent, papular eruptions mainly on

the trunk, upper arms, and occasionally the

face, buttocks, and thighs. Histologically, a

dense perivasc ular inflam mato ry infiltrate

composed of mononuclear cells and many

eosinophils was noted in the upper dermis.

Pemphigoid Noduiaris

Pemphigoid nodularis is an unusual disorder,

described in approximately 20 patients since

1981, predominantly in elderly women [24,25].

Initially, patients present with itchy nodules,

papules, or plaques. Bullae develop later,

sometimes several years after the original

appearance of the noduli. The disorder is

considered to be a variant of buUous pemphi-

goid. Histologically, there is an acanthosis and

direct immunofluorescence reveals a linear

deposition of imm unoglobulin G and C3 in the

epidermal basal membrane zone [24].


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Joanna Wal lengren

rable

. Major topical treatments for prurigo.

Topical treatment

High potency corticosteroids

Pottassium permanganate and

coal tar bath

Cryotherapy

Udocaine

Capsaicin

Menthol

Topical calcineurin inhibitors

Caicipotrioi

Bath PUVA

UVB treatment

Phototherapy

Details

Topical application either under an occiusive membrane or intralesionally.

Used as a first choice therapy in mild forms of prurigo.

Used in severe discharging forms of prurigo. Mode of action is not weii

known because of the number of chemicais that constitute tar. Benefits

are most iii


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Chronic Prurigo: Etiology and Therapy

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Table 2. Major systemic treatmentsforprurigo.

Systemic treatment etails

Antibiotics (erythromycin)

Antihistamines

Systemic PUVA with oral psoralen

Cyclosporin A

Naltrexone

Etretinate and arotinoid acid

Azathioprine

Chioroquine

Dapsone and minocycline

Thalidomide

The single most effective agent in the treatment of prurigo. Administration

should be continued for long periods. [26]

Both sedating and non-sedating can be used to manageitch.

Easy administration and initially strong benefits. Repeated use diminishes

the beneficial effect, impiying that after a while PUVA loses its magic [33].

Good efficacy despite requiring relatively high doses [37].

Orally administered opioid receptor antagonist successful in the

management ofitch.Antipruritic effects found in patients. Contibutory

factor in the heaiing of lesions [38].

Beneficial in the treatment of prurigo resuiting from its effects on ceii

proliferation, differentiation, and inflammation [39,40].

Useful in the treatment of actinic prurigo and prurigo nodularis [41,43].

The drug of choice for actinic prurigo in the young in Mexico. Starting

reiativelyhigh,the dose is reduced by half as the disease improves [43].

Regarded as the treatments of choice for prurigo pigmentosa [44,46].

Potentailly a successful form of treatment. However, concerns over safety

exist because of its tetragenic effects and the possibility of peripheral

neuropathy. The latter risk is mitigated by iow doses. Other minor side

effects include drowsiness and dizziness. Reduction of risk is possible

by using thalidomide prior to narrow-band UVB treatment [47,48].

PUVA: psoralen batb followedbyultraviolet A -irradiation; UVB: ultravioletB.

treatment s most frequently effective n

curing prurigo but palliative treatm ents m ust

also be usedtocontrol the debilitating effect

of chronic itching

Address for correspondence

Joanna Wallengren, Departmentof

Dermatology, University Hospital, SE-22185Lund, Sweden

Email Joanna.Waiiengreniiderm.iu.se

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