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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
3
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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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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