Journal of Dermatological Treatment, 2013; 24: 458–462

© 2013 Informa Healthcare USA on behalf of Informa UK Ltd.

ISSN: 0954-6634 print / 1471-1753 online
DOI: 10.3109/09546634.2013.814759

REVIEW

Prurigo nodularis: an update on etiopathogenesis and therapy

Anna Chiara Fostini, Giampiero Girolomoni & Gianpaolo Tessari

Department of Medicine, Section of Dermatology and Venereology, University of Verona, Verona, Italy

Prurigo nodularis (PN) is a chronic, highly pruritic condition Methods

characterized by the presence of hyperkeratotic, excoriated, We searched PubMed articles using the keywords ‘prurigo
pruritic papules and nodules, with a tendency to symmetrical nodularis’ and ‘nodular prurigo’. A total of 394 articles were
distribution. No reliable data exist about incidence and prevalence retrieved to February 2013. We selected and reviewed those
J Dermatolog Treat Downloaded from informahealthcare.com by University of Laval on 07/07/14

of PN in the general population, but it seems to be more frequent
and more intense in females. PN may be associated with many
dermatological and non-dermatological comorbidities, including
psychiatric disease. Recent findings suggest a neuropathic origin
of PN, with alterations in the dermal and epidermal small diameter
nerve fibers. PN may have a tremendous impact on the quality of
life, and few effective treatment options are available. Few
randomized controlled trials (RCT) on the therapy of PN are
available, demonstrating the efficacy of phototherapy alone or
with psoralen, and of topical calcipotriol and topical steroids in
occlusive medications. Thalidomide may be effective, but no RCT
For personal use only.
articles providing relevant information about etiopathogenesis
and therapy of PN. Randomized controlled studies (RCTs)
and, if not available, large case series were considered.
Etiopathogenesis of PN
Aetiology of PN is very poorly understood and only few studies
have described the total incidence and the strength of association
of co-morbidities in a representative cohort of patients (2,5). The
most common dermatological disorder associated to PN is atopic
dermatitis, described also as ‘atopic prurigo’ (6). Systemic diseases
frequently associated to PN are type 2 diabetes mellitus, thyroid

are available and its use is impractical due to the unfavorable disorders, HCV infection, non-Hodgkin lymphoma and psychi-
safety profile. Gabapentin, pregabalin and the neurokinin receptor atric disorders, particularly depression and anxiety (2,5). In some
1 antagonist, aprepitant, seem also to be effective in the therapy cases, no underlying disease is detected (idiopathic PN). A
of PN, but RCTs are still lacking. detailed description of the conditions associated to PN is reported
in Table I. The pathogenesis of PN is still unknown; however,
Key words: nodular prurigo, prurigo nodularis, pathogenesis, RCT, recent findings suggest that PN might be a consequence of chronic
therapy itch induced by neuropathy. Neuropathic itch is a pruritic sen-
sation caused by a primary lesion or dysfunction at any point
along the afferent pathway of the nervous system and it is well
Introduction established in some conditions, including postherpetic neuropa-
thy, brachioradial pruritus and notalgia paresthetica (7). A dis-
Prurigo nodularis (PN) is a chronic-relapsing, highly pruritic,
tinctive characteristic of neuropathic itch is the co-existence of
condition, with a high impact on the quality of life of the patient.
other sensory symptoms as paraesthesia, hyperesthesia or
It is characterized by the presence of several to hundreds hyper-
hypoesthesia, as well as burning, tingling, stinging and heat
keratotic, pruritic papules and nodules, sometimes excoriated or
and cold sensations (7). These symptoms are frequently referred
ulcerated, with a tendency to symmetrical distribution on the
to by PN patients (2). Bharati et al. was able to confirm a
shoulders, on the back, the buttocks and the upper and lower
subclinical neuropathy in a small group of patients with PN,
limbs. Sparing of the upper mid back, known as ‘butterfly sign’, is
by performing nerve conduction studies (8).
distinctive (Figure 1). Incidence and prevalence of PN in the
Nerve fibers morphology and distribution in lesional and
general population are unknown, because in epidemiological
non-lesional skin in PN patients have been repeatedly investi-
studies PN is often included in chronic itchy disorders (1,2).
gated. An increased number of protein gene product 9.5 (PGP
In female patients PN seems to be more prevalent, to occur at an
9.5), p75 nerve growth factor (NGF)-positive and calcitonin gene-
earlier age, and to be more severe than in male patients (3). The
related peptide (CGRP)-positive nerve fibers in the papillary
diagnosis of PN is usually made on clinical basis. Histology can be
dermis of patients with PN has been described (9). Moreover,
helpful, but it is not specific, and it includes irregular epidermal or
the nerves were in close proximity to eosinophils, suggesting a
pseudoepitheliomatous hyperplasia, fibrosis of the papillary der-
functional relationship (10). A significant increased density of
mis with vertically arranged collagen fibers, and a perivascular
dermal substance P-positive nerve fibers in lesional skin of
and interstitial inflammatory infiltrate of lymphocytes, macro-
patients with PN, and also in clinically normally appearing
phages, eosinophils and neutrophils (4). The pathogenesis is still
skin affected by chronic pruritus, if compared to the non-
not fully elucidated, and evidence-based therapies are very
affected skin of the same patients has been described (11).
limited. The aim of this review is to present an update on
Substance P is a well known mediator of itch induction and
etiopathogenesis and evidence-based treatments of PN.

Correspondence: Gianpaolo Tessari, Department of Medicine, Section of Dermatology and Venereology, University of Verona, Piazzale A. Stefani 1,
37126 Verona, Italy. Tel: +39 045 8122547. Fax: +39 045 8027315. E-mail: gianpaolo.tessari@ospedaleuniverona.it
(Received 3 June 2013; accepted 9 June 2013)

A B
Figure 1. A 58-year old woman with prurigo nodularis, with typical
excoriated nodules distributed bilaterally and symmetrically (A). Higher
view of excoriated nodules on the breast (B).
maintenance, and an increased numbers of substance P positive
dermal nerve fibers have been documented also in atopic der-
J Dermatolog Treat Downloaded from informahealthcare.com by University of Laval on 07/07/14
matitis (12). Epidermal keratinocytes and T-lymphocytes infil-
trating skin areas affected by pruritus may be a source of NGF,
which may contribute to the neurohyperplasia, as well as to nerve
fibers sprouting and up-regulation of neuropeptides, especially
substance P (11,13). Fewer studies have investigated the role of
epidermal nerve fibers in PN. The density of intraepidermal PGP
9.5-positive nerve fibres in lesional pruritic skin as well as in non-
pruritic skin of patients with PN was significantly reduced, if
compared to skin biopsies taken from healthy volunteers. In
patients with pruritus lasting longer than 3 years, the reduction
of nerve fibers was more marked in lesional skin, if compared with
For personal use only.
non-lesional skin (14). These findings seem not to be the con-
sequence of a nerve damage induced by chronic scratching,
because in common pruritic conditions, including atopic derma-
titis, there is sprouting of epidermal nerve fibers (12,15). The
authors concluded that the reduced density of epidermal nerve
fibers, also found in uninvolved skin, is possibly related to a
subclinical small-fibers sensory neuropathy pre-existing to PN
that may be the main driving factor (14). Other studies, however,
reported contrasting results, including increased numbers of PGP
9.5-positive epidermal nerves in lesional PN skin (16), and
hyperproliferation of cutaneous nerves, with enhanced NGF
and reduced semaphorin 3A expression, compared with healthy
subjects (17). These conflicting results are possibly due to differ-
ences in investigation techniques, and the small number and,
most important, heterogeneity of patients enrolled. The hypoth-
esis of the neuropathic origin of PN is also supported by the
observation that topical and systemic treatments used in neuro-
pathic itch and pain, such as capsaicin, gabapentin and prega-
balin, reduce itch intensity and the number of cutaneous lesions in
PN patients (7,8,18–20). Moreover, small fibers neuropathies,
selectively involving Ad-fibres and C-fibres, are characterized
by low intra-epidermal nerve fiber density in skin biopsies, and
are associated with systemic diseases common to PN (21).
Some cytokines may play a role in the pathogenesis of PN (22).
The involvement of Th2-mediated inflammatory responses in the
pathogenesis of PN has been hypothesized given a high expression
of the STAT6 transcription factor in lesional epidermis, which is
typically induced by IL-4 and IL-13. However, also STAT3
expression has been detected. This transcription factor is induced
primarily by IL-22, and to less extent by IFN-g . Interestingly
enough, IL-22 promotes keratinocyte proliferation and it is highly
expressed in atopic dermatitis skin (23). In PN patients with a
history of atopic dermatitis, plasma levels of IL-31 were signif-
icantly increased and correlated with the expression of IL-4 and
IL-13 (24). These observations suggest that PN is a dermatosis
with the preferential involvement of Th2 cytokines, and they
Pathogenesis and therapy of PN 
support, together with the presence of dermal nerve fibers
hyperplasia, the strict correlation between PN and atopic
dermatitis.
Treatment of PN
Treatment of PN is still a challenge, and it is frustrating for both
dermatologists and patients because, in the majority of cases, the
response is limited and unsatisfactory. There is no standardized
therapy of PN, and evidence from RCT is limited. Treatments
include topical, systemic and physical approaches (Table II).
Topical therapy.
Topical agents are used when the disease affects limited skin areas.
A bilateral paired RCT on 12 patients, comparing an occlusive
dressing of beta-methasone valerate 0.1% and moisturizing cream
revealed significant improvement on both sides of the body, but
beta-methasone valerate showed a higher clinical response (VAS
from 8.75 to 3.9) compared with moisturizing itch relief cream
(VAS from 8.75 to 5.63). The improvement obtained with mois-
turizing cream may be due to the relief to the skin xerosis which is
common in patients with PN (25). A double-blind, right/left RCT
compared the efficacy and tolerability of 50 mg/g calcipotriol
ointment with 0.1% betamethasone valerate ointment on 10 sub-
jects affected by PN, showing that calcipotriol ointment was more
effective and cleared prurigo nodules more rapidly than beta-
methasone valerate ointment (26). In a case series of 11 patients
with chronic pruritus and PN refractory to other therapies, the
topical calcineurin inhibitors, tacrolimus and pimecrolimus,
induced a complete response in 3/11 PN patients, a partial
response in 4/11 patients and no effect in the other patients (27).
Systemic therapy.
No studies have formally investigated the effectiveness of oral
antihistamines and systemic steroids, as well as other immuno-
suppressive agents although they are commonly used in PN.
Systemic agents, which have been recently investigated, include
antiepileptics (gabapentin, pregabalin), thalidomide, neurokinin
receptor 1 (NKR1) antagonist (aprepitant), and the m-opioid
receptor antagonist, naltrexone. Gabapentin and pregabalin block
neuron calcium channels and increase the concentration of
gamma-amino butyric acid (GABA) in the brain. They have
anti-convulsive activity, and are also used for the treatment of
neuropathic pain syndromes such as diabetic neuropathy and
postherpetic neuralgia, and epilepsy neuropathic pain with spinal
cord injury. Gabapentin and pregabalin have proven their anti-
pruritic activity in dialysis related pruritus, and in post-
burn pruritus in RCTs (28,29). Only two case series investigated
the use of gabapentin in PN. In a case series of nine patients, five
affected by chronic pruritus and four affected by PN, gabapentin
significantly improved itching at a dosage of 300–900 mg per day
for 2–10 months (18). Of 30 PN patients treated with pregabalin
(75 mg/die for 3 months), 23 (76%) showed a complete response,
and the therapy was unsuccessful just in one case. Sedation
appeared only in three patients (19). Gabapentin is not metab-
olized in the liver and is excreted unmodified in the urine.
Posology should be reduced according to creatinine clearance
in patients with severe renal impairment, or in elderly people.
Caution must be used in pregnant and lactating women because it
is included in pregnancy category C and it enters in breast milk.
Thalidomide acts as an immunomodulatory drug, a tumor
necrosis factor-a inhibitor, as well as a peripheral and central
nerve depressant. It is approved for treating erythema nodosum
leprosum and multiple myeloma, but it has also proven to be
useful in many dermatologic disorders refractory to conventional
therapies (30). No RCT on the use of thalidomide in PN are
  A. C. Fostini et al.

Table I. Prurigo nodularis: reported associated diseases (2,5,6,42). onset of peripheral neuropathy and sedation, or the lack of
Cutaneous diseases efficacy (31). Similar findings were reported in other smaller
Atopic dermatitis case series using thalidomide at a daily dose of 50–200 mg
Contact allergy (32–36). In a case series of 13 PN patients treated with lower
Insect bites doses of thalidomide (50–100 mg daily), 84% of patients showed a
Nummular eczema moderate-to-good response (32). Other common side effects of
Infections thalidomide are constipation, dizziness, rash, edema, dryness,
Atypical mycobacteria pruritus, neutropenia, bradycardia, tachycardia, hypotension,
Helicobacter pylori headache, mood changes, nausea, increased appetite, weight
Hepatitis B virus gain, male sexual dysfunction, amenorrhea, ovarian failure and
Hepatitis C virus thrombosis (31). Thalidomide is teratogen, and adequate con-
Human immunodeficiency virus traceptive measures are required for 4 weeks prior to beginning
Strongyloides stercoralis therapy, during therapy and for 4 weeks after discontinuation,
Lymphoproliferative diseases and tumours both for woman and for man.
Carcinoma of the bladder Aprepitant is a selective high-affinity NKR1-antagonist, which
Gastric cancer prevents substance P to bind its receptor. Its registered indication
Hodgkin’s disease is the prevention of vomit and nausea induced by chemotherapy
in oncologic patients at the posology of 80–125 mg daily for 3 days
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Leiomyomatosis peritonealis disseminata

Lennert’s lymphoma before starting chemotherapy. A study by Ständer et al. revealed
Non-Hodgkin B-cell lymphoma that its administration at dose of 80 mg once daily for 1 week led
Miscellaneous to a significant reduction of pruritus on 13 PN patients, showing a
Alpha-1 antitrypsin deficiency mean VAS reduction of about 50% and a clinical improvement of
Aluminum overload in haemodialysis scratch lesions (37).
Anaemia Naltrexone is an oral competitive antagonist at m-opioid
Psychiatric disorders receptor, which has been used in the treatment of pruritus
Atopy associated with a variety of dermatologic and systemic diseases,
Etretinate treatment such as PN, mycosis fungoides, lichen simplex, but RCT exist only
Gluten enteropathy for cholestatic pruritus, chronic urticaria and atopic dermatitis
(38). A case series of 133 patients with pruritus caused by
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Hepatic dysfunction
Myxoedema inflammatory skin diseases showed that naltrexone 50–150 mg
Primary sclerosing cholangitis daily was most effective in PN, pruritus due to cutaneous
Uremia lymphoma and pruritus of unknown origin (39), revealing an
Venous stasis anti-pruritic effect in 67.7% of patients. Naltrexone is contra-
Diabetes mellitus I indicated in patients with acute hepatitis, liver failure, severe liver
Thyroid disorders insufficiency and marginal evidence of hepatocellular injury (38).

available. The largest retrospective study included 42 PN
patients who were refractory to topical, systemic and intrale-
sional steroids, phototherapy and other treatments. Thirty-
two patients experienced clinical improvement after a median
duration of treatment with thalidomide of 105 weeks at the
average dose of 100 mg daily. Complete clearing was observed in
1 patient, improvement in 31 patients and no effect in 6 patients.
Most common reasons for treatment discontinuation were the
Physical therapy.
Phototherapy is commonly used in various inflammatory skin
diseases and the anti-inflammatory effect of UV-light exposure
and the ability of UV light to diminish pruritus has been
confirmed in several inflammatory cutaneous disorders, including
atopic dermatitis, lichen ruber planus and PN (40). Broadband
UVB radiation, sequential combined treatment of UVB irradia-
tion and topical psoralen UVA, a combination of thalidomide and
narrowband UVB, and treatment with UVA and monochromatic

Table II. Current evidence based therapies of prurigo nodularis.

Study design Type of drug No of patients References
RCT Betamethasone valerate 0.1% tape vs. moisturizing itch relief cream 12 (25)
RCT Calcipotriol ointment (50 mg/g) vs. betamethasone valerate ointment 0.1% 10 (26)
RCT Bath PUVA vs. bath PUVA + targeted UVB 308 nm excimer light 22 (40)
CS Pregabalin (75 mg p.o. daily for 3 months) 30 (19)
CS Gabapentin (300–900 p.o. mg daily) 9 (4: PN) (18)
CS Aprepitant: (80 mg p.o. daily for 3–13 days) 20 (13: PN) (37)
CS Cyclosporine microemulsion (3–5 mg/kg p.o. daily) 14 (43)
CS Roxithromycin (300 mg + tranilast 200 mg p.o. daily) 3 (44)
CS Thalidomide (50–200 mg p.o. daily) 13 (32)
CS Thalidomide 42 (31)
CS Thalidomide 48 (PN and other skin conditions) (33)
CS Thalidomide (50–100 mg p.o. daily) 6 (34)
CS Thalidomide (100–200 mg p.o. daily) 25 (1: PN) (35)
CS Intranasal butorphanol (1 mg/d) 5 (1: PN) (45)
CS Topical calcineurin inhibitors 20 (11: PN) (27)
RCT: Randomized controlled study; CS: case series; p.o.: per os.

excimer light (308 nm) have all been used with variable results in
the treatment of PN (41). Hammes et al. enrolled in a RCT
22 patients with PN, refractory to topical or intralesional corti-
costeroids administered for at least 6 months, and compared bath
PUVA four times a week at increasing doses from the MED of
0.2–0.3 J/cm2 every three treatments (maximum of 3.5 J/cm2),
with a combination of bath PUVA and targeted UVB 308 nm
excimer laser radiation at a fixed repetition rate of 200 Hertz at an
intensity of 400 mW/cm2. Improvement was obtained in both
groups. No significant differences were detected in the number of
remissions, but PUVA monotherapy group needed 30% more
PUVA radiation to achieve the same benefit (40). Other case
series have been published using phototherapy in patients pre-
senting different cutaneous diseases included PN, but the number
of PN subjects included is too small to draw any meaningful data.
In the most recent case series, 19 patients affected by PN resistant
to topical steroids were treated with a UV lamp emitting mainly in
the UVA range, with a spike at 390 nm, for a median number of
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23 phototherapy treatments (range 7–37) with a mean total dose
of 6.07 J/cm2. About 80% of them had an improvement in their
clinical condition after treatment. Two patients obtained complete
remission, eight marked improvement, five slight improvement
and four (21.1%) had no response (41).
Conclusions
PN is a chronic and very disabling disease, which may have a
remarkable impact on quality of life. Recent findings suggest a
neuropathic origin of the disease, which might be considered a
For personal use only.
sub-type of small fiber neuropathy, but further studies are
needed to better substantiate this hypothesis. PN is associated
with many dermatological and non-dermatological comorbid-
ities, but limited data support the existence of a clear cause–
effect relationship. PN is a heterogeneous disorder, and subset
definition may be very important also for the design of new
therapeutic trials. Few RCT on the treatment of PN are available.
No regimen seems more effective than other, as comparative
studies are still lacking. Phototherapy is considered effective and
safe, but can be impractical for many patients. Promising results
have been anticipated with gabapentin and pregabalin, but
RCTs are still lacking. The efficacy of NKR1 antagonists needs
to be confirmed in larger multicenter studies. Most likely,
patients with PN need to be approached with combination
therapy, which includes suppression of multiple mediators,
including cytokines and neuromediators.
Declaration of interest: The authors report no conflicts of
interest. The authors alone are responsible for the content and
writing of the paper.
References
1. Weisshaar E, Szepietowski JC, Darsow U, Misery L, Wallengren J,
Mettang T, et al. European guideline on chronic pruritus. Acta Derm
Venereol. 2012;92:563–581.
2. Iking A, Grundmann S, Chatzigeorgakidis E, Phan NQ, Klein D,
Ständer S. Prurigo as a symptom of atopic and non-atopic diseases:
aetiological survey in a consecutive cohort of 108 patients. J Eur Acad
Dermatol Venereol. 2013;27:550–557.
3. Ständer S, Stumpf A, Osada N, Wilp S, Chatzigeorgakidis E,
Pfleiderer B. Gender differences in chronic pruritus: Women present
different morbidity, more scratch lesions and higher burden. Br J
Dermatol. 2013;168:1273–1280.
4. Weigelt N, Metze D, Ständer S. Prurigo nodularis: systematic analysis
of 58 histological criteria in 136 patients. J Cutan Pathol. 2010;37:
578–586.
Pathogenesis and therapy of PN 
5. Winhoven SM, Gawkrodger DJ. Nodular prurigo: metabolic diseases
are a common association. Clin Exp Dermatol. 2007;32:224–225.
6. Pugliarello S, Cozzi A, Gisondi P, Girolomoni G. Phenotypes of atopic
dermatitis. J Dtsch Dermatol Ges. 2011;9:12–20.
7. Yosipovitch G, Samuel LS. Neuropathic and psychogenic itch. Der-
matol Ther. 2008;21:32–41.
8. Bharati A, Wilson NJE. Peripheral neuropathy associated with nodular
prurigo. Clin Exp Dermatol. 2007;32:67–70.
9. Liang Y, Jacobi HH, Reimert CM, Haak-Frendscho M, Marcusson JA,
Johansson O. CGRP-immunoreactive nerves in prurigo nodularis–an
exploration of neurogenic inflammation. J Cutan Pathol. 2000;27:359–
366.
10. Johansson O, Liang Y, Marcusson JA, Reimert CM. Eosinophil cationic
protein- and eosinophil-derived neurotoxin/eosinophil protein X--
immunoreactive eosinophils in prurigo nodularis. Arch Dermatol
Res. 2000;292:371–378.
11. Haas S, Capellino S, Phan NQ, Böhm M, Luger TA, Straub RH, et al.
Low density of sympathetic nerve fibers relative to substance P-positive
nerve fibers in lesional skin of chronic pruritus and prurigo nodularis.
J Dermatol Sci. 2010;58:193–197.
12. Emtestam L, Hagströmer L, Dou Y-C, Sartorius K, Johansson O. PGP
9.5 distribution patterns in biopsies from early lesions of atopic
dermatitis. Arch Dermatol Res. 2012;304:781–785.
13. Johansson O, Liang Y, Emtestam L. Increased nerve growth factor- and
tyrosine kinase A-like immunoreactivities in prurigo nodularis skin –
an exploration of the cause of neurohyperplasia. Arch Dermatol Res.
2002;293:614–619.
14. Schuhknecht B, Marziniak M, Wissel A, Phan NQ, Pappai D,
Dangelmaier J, et al. Reduced intraepidermal nerve fibre density in
lesional and nonlesional prurigo nodularis skin as a potential sign of
subclinical cutaneous neuropathy. Br J Dermatol. 2011;165:85–91.
15. Ikoma A, Steinhoff M, Ständer S, Yosipovitch G, Schmelz M. The
neurobiology of itch. Nat Rev Neurosci. 2006;7:535–547.
16. Abadía Molina F, Burrows NP, Jones RR, Terenghi G,
Polak JM. Increased sensory neuropeptides in nodular prurigo:
a quantitative immunohistochemical analysis. Br J Dermatol. 1992;
127:344–351.
17. Takada S, Kou K, Ikezawa Z, Aihara M. Aberrant epidermal expression
of semaphorin 3A and nerve growth factor in prurigo nodularis.
J Dermatol. 2013;40:1–2.
18. Gencoglan G, Inanir I, Gunduz K. Therapeutic hotline: Treatment of
prurigo nodularis and lichen simplex chronicus with gabapentin.
Dermatol Ther. 2010;23:194–198.
19. Mazza M, Guerriero G, Marano G, Janiri L, Bria P, Mazza S. Treatment
of prurigo nodularis with pregabalin. J Clin Pharm Ther. 2013;38:16–
18.
20. Ständer S, Luger T, Metze D. Treatment of prurigo nodularis with
topical capsaicin. J Am Acad Dermatol. 2001;44:471–478.
21. Hoeijmakers JG, Faber CG, Lauria G, Merkies IS, Waxman SG. Small--
fibre neuropathies–advances in diagnosis, pathophysiology and man-
agement. Nat Rev Neurol. 2012;8:369–379.
22. Fukushi S, Yamasaki K, Aiba S. Nuclear localization of activated
STAT6 and STAT3 in epidermis of prurigo nodularis. Br J Dermatol.
2011;165:990–996.
23. Sestito R, Madonna S, Scarponi C, Cianfarani F, Failla CM,
Cavani A, et al. STAT3-dependent effects of IL-22 in human kerati-
nocytes are counterregulated by sirtuin 1 through a direct inhibition of
STAT3 acetylation. FASEB J. 2011;25:916–927.
24. Sonkoly E, Muller A, Lauerma AI, Pivarcsi A, Soto H, Kemeny L, et al.
IL-31: a new link between T cells and pruritus in atopic skin inflam-
mation. J Allergy Clin Immunol. 2006;117:411–417.
25. Saraceno R, Chiricozzi A, Nisticò SP, Tiberti S, Chimenti S. An
occlusive dressing containing betamethasone valerate 0.1% for the
treatment of prurigo nodularis. J Dermatolog Treat. 2010;21:363–366.
26. Wong SS, Goh CL. Double-blind, right/left comparison of calcipotriol
ointment and betamethasone ointment in the treatment of Prurigo
nodularis. Arch Dermatol. 2000;136:807–808.
27. Ständer S, Schürmeyer-Horst F, Luger TA, Weisshaar E. Treatment of
pruritic diseases with topical calcineurin inhibitors. Ther Clin Risk
Manag. 2006;2:213–218.
28. Razeghi E, Eskandari D, Ganji MR, Meysamie AP, Togha M,
Khashayar P. Gabapentin and uremic pruritus in hemodialysis
patients. Ren Fail. 2009;31:85–90.
29. Ahuja RB, Gupta GK. A four arm, double blind, randomized and
placebo controlled study of pregabalin in the management of post-burn
pruritus. Burns. 2013;39:24–29.
30. Chen M, Doherty SD, Hsu S. Innovative uses of thalidomide. Dermatol
Clin. 2010;28:577–586.
  A. C. Fostini et al.
31. Andersen TP, Fogh K. Thalidomide in 42 patients with prurigo
nodularis Hyde. Dermatology. 2011;223:107–112.
32. Taefehnorooz H, Truchetet F, Barbaud A, Schmutz J-L, Bursztejn
A-C. Efficacy of thalidomide in the treatment of prurigo nodularis.
Acta Derm Venereol. 2011;91:344–345.
33. Doherty SD, Hsu S. A case series of 48 patients treated with thalid-
omide. J Drugs Dermatol. 2008;7:769–773.
34. Lan C-CE, Lin C-L, Wu C-S, Chai C-Y, Chen W-T, Chen G-S. Treatment
of idiopathic prurigo nodularis in Taiwanese patients with low-dose
thalidomide. J Dermatol. 2007;34:237–242.
35. Sharma NL, Sharma VC, Mahajan VK, Shanker V, Ranjan N,
Gupta M. Thalidomide: an experience in therapeutic outcome and
adverse reactions. J Dermatolog Treat. 2007;18:335–340.
36. Maurer T, Poncelet A, Berger T. Thalidomide treatment for prurigo
nodularis in human immunodeficiency virus-infected subjects: efficacy
and risk of neuropathy. Arch Dermatol. 2004;140:845–849.
37. Ständer S, Siepmann D, Herrgott I, Sunderkötter C, Luger TA. Target-
ing the neurokinin receptor 1 with aprepitant: a novel antipruritic
strategy. PLoS One. 2010;5:e10968.
38. Phan NQ, Bernhard JD, Luger TA, Ständer S. Antipruritic treatment
with systemic m-opioid receptor antagonists: a review. J Am Acad
J Dermatolog Treat Downloaded from informahealthcare.com by University of Laval on 07/07/14
Dermatol. 2010;63:680–688.
For personal use only.
39. Brune A, Metze D, Luger TA, Ständer S. Antipruritic therapy with
the oral opioid receptor antagonist naltrexone. Open, non-placebo
controlled administration in 133 patients. Hautarzt. 2004;55:1130–
1136.
40. Hammes S, Hermann J, Roos S, Ockenfels HM. UVB 308-nm excimer
light and bath PUVA: combination therapy is very effective in the
treatment of prurigo nodularis. J Eur Acad Dermatol Venereol. 2011;
25:799–803.
41. Bruni E, Caccialanza M, Piccinno R. Phototherapy of generalized
prurigo nodularis. Clin Exp Dermatol. 2010;35:549–550.
42. Cassano N, Tessari G, Vena GA, Girolomoni G. Chronic pruritus
in the absence of specific skin disease: an update on pathophys-
iology, diagnosis, and therapy. Am J Clin Dermatol. 2010;11:399–
411.
43. Siepmann D, Luger TA, Ständer S. Antipruritic effect of cyclosporine
microemulsion in prurigo nodularis: results of a case series. J Dtsch
Dermatol Ges. 2008;6:941–946.
44. Horiuchi Y, Bae S, Katayama I. Uncontrollable prurigo nodularis
effectively treated by roxithromycin and tranilast. J Drugs Dermatol.
2006;5:363–365.
45. Dawn AG, Yosipovitch G. Butorphanol for treatment of intractable
pruritus. J Am Acad Dermatol. 2006;54:527–531.