Dermatologic Therapy, Vol.

23, 2010, 194198

Printed in the United States All rights reserved

2010 Wiley Periodicals, Inc.

DERMATOLOGIC THERAPY
ISSN 1396-0296

THERAPEUTIC HOTLINE
Treatment of prurigo nodularis and
lichen simplex chronicus
with gabapentin
Gulsum Gencoglan, Isil Inanir & Kamer Gunduz
Department of Dermatology, Medical Faculty of Celal Bayar University,
Turkey

ABSTRACT: Psychocutaneous conditions are frequently encountered in dermatology practice. Prurigo

nodularis and lichen simplex chronicus are two frustrating conditions that are classified in this category. They are often refractory to classical treatment with topical corticosteroids and antihistamines.
Severe, generalized exacerbations require systemic therapy. Phototherapy, erythromycine, retinoids,
cyclosporine, azathiopurine, naltrexone, and psychopharmacologic agents (pimozide, selective serotonin reuptake inhibitor antidepressants) were tried with some success. Here five cases with lichen
simplex chronicus and four cases with prurigo nodularis, who responded well to gabapentin, are
presented.
KEYWORDS: gabapentin, lichen simplex chronicus, prurigo nodularis, pruritus, therapy

Introduction

dth_1314

194..198

Psychocutaneous conditions are frequently

encountered in dermatology practice. At least one
third of dermatology outpatients require consideration of associated emotional and psychosocial
factors (1). Emotional stress especially plays a key
role in inducing itch, followed by scratching.
Prurigo nodularis (PN) and lichen simplex chronicus (LSC) are two frustrating conditions classified
in this category (2,3).
Prurigo nodularis is characterized by multiple
firms, generally 0.52 cm-sized papules and
nodules, whereas LSC appears as lichenified, thickened palm-sized plaques. These two conditions
Address correspondence and reprint requests to: Gulsum
Gencoglan, MD, Assistant Professor, Department of
Dermatology, Medical Faculty of Celal Bayar University, 45030
Manisa, Turkey, or email: gencoglan75@hotmail.com.

194

have several similarities and some authors have

grouped them together (2). Intense pruritus and
scratching are the main symptoms and strictly correlate to the persistence and the progression of skin
lesions. Patients report having temporary relief with
scratching. Thickening, pigmentation, and rarely
ulceration are clinical features. Atopy and an associated systemic pruritic disorder may be associated
with these two disorders. Psychogenic factors play a
dominant role in both; pruritus becomes worse,
lesions are induced and triggered with stress.
Related with the unclear pathogenesis, treatment of PN and LSC is difficult. Topical antipruritic
agents, corticosteroids, calcineurin inhibitors and
capsaicin, systemic antihistamines, and phototherapy mainly have been used to treat these diseases (2,4). In calcitrant and severe forms of PN,
cyclosporine, thalidomide, opiate receptor antogonists, laser, and naltrexone have been used
with variable success (46). Herein, we describe

Prurigo nodularis and lichen simplex chronicus

five patients with LSC, and four patients with PN,

who responded well to gabapentin, are presented.

Patients and methods

All nine patients (four with PN and five with LSC)
were treated with gabapentin. Four males and five
females with an average age of 44.8 years had
severely pruritic papules and nodules existing for
220 years. Lesions were only on extremities in
three patients; the other six patients also had
truncal involvement. All nine patients been treated
with antihistamines, corticosteroids, phototherapy, and antidepressants. Gabapentin 300 mg/
day treatment was initiated and the dosage was
gradually increased to 900 mg/day (300 mg/day, 3
days; 600 mg/day, 3 days, and finally 900 mg/day).
The patients were seen every month. Improvement
was assessed, with pruritus severity evaluated by
the patient and clinical observation carried out by
a physician. Data on the patients medical history
and therapy are shown in Table 1.

Results
After 2 months, all patients had at least partial
remission. This improvement continued in seven
patients throughout the therapy period, except in
the first patient (Table 2). This patient had severe
anxiety and depression and stopped gabapentin
after 4 months when his lesions had gone worse.
Gabapentin was used 900 mg daily for 3 or 4
months until a desired effect was achieved. In
patients 2 and 6, response to gabapentin was sufficient so that it was discontinued after 3 months. In
the remaining patients, gabapentin was reduced
gradually from 600 mg/day to 300 mg/day. Total
treatment period ranged from 4 to 10 months.
Patients were followed for 3 months after stopping
gabapentin, and the clinical improvement was
consistent in the follow-up period (Table 1). Half of
the patients reported mild pruritus at the end of
the therapy and in the follow-up period, but their
lesions have not recurred. In all patients pruritus
was never as severe as in the beginning and what
was present responded to topical lubricants. No
side effect was experienced, except tolerable sedation in three patients (FIG. 1).

Discussion
Pruritus is an unpleasant sensation that induces a
desire to scratch. This complex process involves

FIG. 1. (a) Before treatment. (b) After treatment.

the stimulation of free nerve endings in the skin

and transmission through the C fibers to the dorsal
horn of the spinal cord, and then, via the spinothalamic tract to the cerebral cortex for processing.
Along with scratching, inflammatory mediators
such as histamine, serotonin, cytokines, and
opioids which induce or aggravate pruritus are
released, resulting in an itchscratch cycle (7).
Scratching and rubbing lead to several skin conditions like PN and LSC, which are generally resistant
to therapy. Our patients did not respond to several
topical or oral medications given previously.
Gabapentin is a potent anticonvulsant also
used for the treatment of neuropathic pain syndromes such as diabetic neuropathy and postherpetic neuralgia (810). Itch follows similar
neural pathways to pain from skin to the sensory
cortex, thus leading to the use of gabapentin for
pruritus. In recent years, the efficacy of gabapentin for notalgia paresthetica (11), uremic (12), brachioradial (13,14), idiopathic (15), and post-burn
pruritus (16) has been reported. Dereli et al.
reported a patient with PN treated successfully
with gabapentin (5).
The action mechanism of gabapentin on pruritus is unknown; however, various hypotheses have
been suggested. Pruritus is a nociceptive stimulus
and gabapentin was shown to increase the threshold of nociception (17). Its primary effect may be
related to an increase in the concentration of the
excitatory neurotransmitter gamma-aminobutyric
acid (GABA) as in pain syndromes. Gabapentin
blocks the calcium channels located in the spinal
cord and inhibits the release of GABA as wells as
increasing the synthesis of GABA by altering the
activity of glutamic acid decarboxylase (10). An
increase in GABA in the spinal cord secondarily

195

Gencoglan et al.

Table 1. Medical data of the patients

Duration
of disease
(years)

Patient
no.

Age

Sex

17

2.5

39

78

20

21

15

40

10

52

53

29

58

46

15

Previously admitted therapy

Hydroxyzine hydrochloride
Loratadin
Escitalopram
Amitriptyline HCL
Topical corticosteroids
Hydroxyzine hydrochloride
Desloratadin
Cetirizine hydrochloride
Methyl prednisolone
(30 mg/day)
Cetirizine hydrochloride
Amitriptyline HCL
Mianserin HCL
Topical corticosteroids
Emollients
UVB
Hydroxyzine hydrochloride
Cetirizine hydrochloride
Dapson
Prednisolone 302 mg/day
Amitriptyline HCL
Sertralin HCL
Topical corticosteroids
Hydroxyzine hydrochloride
Loratadin
Amitriptyline HCL
Sertralin HCL
Topical corticosteroids
Hydroxyzine hydrochloride
Acrivastin
Cetirizine hydrochloride
Topical corticosteroids
Acrivastin
Cetirizine hydrochloride
Hydroxyzine hydrochloride
Loratadin
Topical corticosteroids
Loratadin
Hydroxyzine hydrochloride
Acrivastin
Topical corticosteroids
Acrivastin
Cetirizine hydrochloride
Hydroxyzine hydrochloride
Loratadin
Topical corticosteroids

Medical
history

Therapy period (months)

Duration of
remission
(months)

Anxiety
disorder

4 months (900 mg/day)

None

3 months (900 mg/day)

COPD

3 months (900 mg/day)

+
3 months (600 mg/day)
+
4 months (300 mg/day)

10

None

3 months (900 mg/day)

+
3 months (600 mg/day)
+
4 months (300 mg/day)

None

4 months (900 mg/day)

+
2 months (600 mg/day)
+
4 months (300 mg/day)
3 months (900 mg/day)

Diabetes
Hypertension
Hyperlipidemia

10

None

4 months (900 mg/day)

+
2 months (600 mg/day)

Diabetes
Hyperlipidemia

4 months (900 mg/day)

+
2 month (600 mg/day)

None

1 months (900 mg/day)

+
3 months (600 mg/day)
+
4 months (300 mg/day)

COPD, chronic obstructive pulmonary disease; HCL, hydrochloric acid; UVB, ultraviolet B.

inhibits release of calcitonin gene-related peptide

(CGRP, an itch mediator) from afferent neurons. It
also affects central itching by modulating m-opioid
receptors (15). Opioid peptides also have a peripheral action, potentiating itching due to other
agents. The origins of pruritus in the conditions
noted above are not well understood but may be
peripheral, central, and psychogenic (18). There-

196

fore, more than one mechanism seems to be associated with the effect of gabapentin.
Another therapeutic, botulinum toxin, has also
been found useful in pruritic syndromes of notalgia
paresthetica and lichen simplex (19,20). It inhibits
the release of substance P and CGRP like gabapentin. It seems that the antipruritic effects of both
drugs depend upon at least these itch mediators.

Prurigo nodularis and lichen simplex chronicus

Table 2. Outcome of the therapy

Intensity of pruritus

Status of the lesions

Patient no.

Pretreatment

2 months

End of the therapy

2 months

End of the therapy

1
2
3
4
5
6
7
8
9

Severe
Severe
Severe
Severe
Severe
Severe
Severe
Severe
Severe

Slight
Slight
Moderate
Moderate
Slight
Slight
Slight
Slight
Moderate

Very intense
Slight
Slight
Slight
None
None
None
None
Slight

Partial remission
Partial remission
Partial remission
Partial remission
Complete remission
Partial remission
Partial remission
Partial remission
Partial remission

No remission
Complete remission
Complete remission
Complete remission
Complete remission
Partial remission
Complete remission
Complete remission
Partial remission

Therapeutic dosing of gabapentin is different in

various trials. It is generally started at 300 mg daily
dose and increased with the same amount in neuropathic syndromes. Besides the most common
adverse effect of sedation, it can rarely cause pancytopenia, cholestasis, hypersensitivity syndrome,
and dyskinesia. It has been safely dosed to a
maximum of 3600 g/day (21). In pruritic conditions, it was found to be effective with doses
of 600 mg/day for notalgia paresthetica (11),
1200 mg/day for PN (5), and 1800 mg/day for generalized pruritus (15). It is hard to have a consensus
on dosing with these case reports, but all doses
reported were under the safety margin. Pruritus
was controlled with 900 mg/day in our patients,
and only a few tolerable side effects were observed.
We suggest starting with 300 mg/day and increasing gradually until the effective minimal dose.
In conclusion, we suggest that gabapentin might
be an important alternative in patients with chronic
prurigo. Although it has been used for several neuropathic pain disorders and pruritus of different
disorders, there is only one case report on the efficacy of gabapentin in chronic PN (5). The small
number of patients in our study, the uncontrolled
and retrospective nature of the study, the unequal
follow-up periods, and treatment schedules are the
limitations of this report. Controlled trials are indicated to confirm our results in addition to a more
uniform dosing. The results of therapy with gabapentin in our patients are encouraging.

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