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The role of hydroxychloroquine in the treatment of lichen planopilaris: A

retrospective case series and review: NIC DHONNCHA et al.

Article  in  Dermatologic Therapy · February 2017

DOI: 10.1111/dth.12463

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DOI: 10.1111/dth.12463

ORIGINAL PAPERS

The role of hydroxychloroquine in the treatment of lichen

planopilaris: A retrospective case series and review

E. Nic Dhonncha | C. C. Foley | T. Markham

Department of Dermatology, University

Hospital Galway, Galway, Ireland
Abstract
Correspondence A variety of systemic agents are used to treat lichen planopilaris (LPP) with a limited evidence base.
Eilis Nic Dhonncha, Department of The aim of our study was to retrospectively review the response rate to and tolerability of hydroxy-
Dermatology, University Hospital, Galway, chloroquine in a cohort of patients with LPP in an effort to add to the evidence base for its use.
Ireland.
Twenty-three patients with a clinical and histopathological diagnosis of LPP who had been treated
Email: e.nicdhonncha1@gmail.com
with hydroxychloroquine for their disease in a single center were identified. A retrospective review of
Funding information
None. these patients’ medical records was performed and physician rated response was documented. Com-
plete response was observed in 61% of our patients, and a further 9% of patients demonstrated
partial response. Thirteen percent of patients withdrew from treatment because of suspected adverse
effects. Our sample size was small, and data was collected retrospectively. We found hydroxychloro-
quine to be a reasonable therapeutic choice in LPP.

KEYWORDS
alopecia, hydroxychloroquine, lichen planopilaris, treatment

1 | INTRODUCTION
Lichen planopilaris (LPP) is a form of scarring hair loss seen most com-
monly in women. The scarring alopecias all have in common a targeted
folliculocentric attack which leads to irreversible follicular destruction
and permanent hair loss. LPP, first described by Pringle in 1985, is the
prototypical scarring alopecia caused by chronic lymphocytic inflamma-
tion around the upper portion of the hair follicle (Chiang, Sah, Cho,
Ochoa, & Price, 2010), and is characterized by patchy scarring alopecia
throughout the scalp. The reported annual incidence rate in the United
States ranges from 1.15 to 7.59% among all new patients with hair loss
(Ochoa, King, & Price, 2008).
No effective treatment regimens for LPP have been established,
although various reports noted some improvement or stabilization with
topical and intralesional corticosteroids, antibiotics, hydroxychloro-
interferes with the binding of antigenic peptides with the class II mole-
cules of the major histocompatibility complex. Presentation to CD41
lymphocytes is thus avoided, thereby inhibiting the production of cyto-
kines that participate in the generation of an inflammatory response. It
is also known to act on a number of other pathways that have anti-
inflammatory, immunomodulatory, anti-proliferative, and photoprotec-
tive effects (Rodriguez-Caruncho & Biesla Marsol, 2014). Hydroxy-
chloroquine is generally well tolerated. Potential side effects include
gastrointestinal upset, neuromuscular symptoms, headaches, skin
rashes, urticaria, and blue/black skin discoloration that resolves on ces-
sation of therapy. Reversible leucopenia can also occur. The risk of reti-
nal toxicity is low in the first 5 years of treatment but increases with
duration of therapy and when occurs can be irreversible.
Although Hydroxychloroquine has shown promising results in the
treatment of LPP in some studies to date, results are inconsistent. The

quine, topical and oral immunomodulators, and 5-alpha reductase aim of our study was to retrospectively review the clinical efficacy and

inhibitors (Ladizinski, Bazakas, Selim, & Olsen, 2013). One reason for tolerability of hydroxychloroquine in the treatment of patients with

the lack of evidence for treatment in LPP is the lack of meaningful LPP in our center.

measurable end points.

Hydroxychloroquine is an antimalarial medication commonly used
since the 1950s in Dermatology to treat a range of conditions including
lupus erythematosus and lichen planus. It is a lysosomotropic drug that
Abbreviation: LPP, lichen planopilaris.
2 | METHODS
All patients with a clinical and histopathological diagnosis of LPP who
attended our center between March 2009 and March 2015, and were
treated with oral hydroxychloroquine for their disease, were identified

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C 2016 Wiley Periodicals, Inc. | 1 of 4
https://doi.org/10.1111/dth.12463
2 of 4 | NIC DHONNCHA
from a patient database. Patients were included in the study if they
had a biopsy-proven diagnosis of LPP, were aged 18 and over, and had
been treated with hydroxychloroquine for LPP at some point. A retro-
spective review of these patients’ medical records was performed, and
the following data was collected: demographics (date of birth, gender,
age at diagnosis), histology results, and treatment to date. Specific to
hydroxychloroquine, we documented dose, duration of treatment, side
effects, disease response, and reason for stopping the medication. All
patients had been diagnosed and treated by a single observer. Full clini-
cal response was defined as absence of reported symptoms, lack of
progression of hair loss, and no evidence on-going disease activity (ery-
thema, and follicular hyperkeratosis) on clinical examination. Partial
clinical response was defined as some noticeable improvement in clini-
cal symptoms and signs, but with evidence of on-going disease activity.
Failed treatment was defined as evidence of on-going disease activity
and progression of hair loss despite an adequate course of
hydroxychloroquine.
3 | RESULTS
3.1 | Patient demographics
A total of 27 patients with a clinicopathologic diagnosis of LPP who
met the inclusion criteria for the study were identified, 92.6% of whom
were female (n 5 25). Patients ranged between the ages of 23 and
77 years at diagnosis, with an average age of 56.3 years and median
age of 60 years. Mean age at diagnosis was younger in males than
females (42.5 years and 57.4 years, respectively).
3.2 | Treatment
Twenty-three patients with LPP met the criteria for analysis of treat-
ment with hydroxychloroquine. Those who did not attend a follow-up
appointment, or were referred elsewhere for their follow-up were not
included in the final analysis. At the time of chart review, 18 patients
had completed or stopped treatment with hydroxychloroquine, and 5
patients were receiving on-going treatment with hydroxychloroquine.
The vast majority of patients (95.7%, n 5 22) had started at a dose of
200 mg twice daily, reducing to once daily if and when their condition
was deemed well controlled by the treating consultant dermatologist.
Mean duration of treatment with hydroxychloroquine was 13.3
months (range 5 1–44). The majority of patients tolerated treatment
well with no reported adverse effects (78.2%, n 5 18). Four patients
(17.4%) experienced suspected adverse effects which resulted in with-
drawal of treatment in three cases; due to dyspnoea, dry eyes, and urti-
caria, respectively. Of note, all three of these patients stopped
treatment themselves without consulting their treating dermatologist.
The symptoms resolved spontaneously in all three patients on with-
drawal of hydroxychloroquine, and none of these patients were re-
challenged with hydroxychloroquine. No retinopathy was encountered.
One patient developed transient leucopenia and thrombocytopenia,
which resolved spontaneously despite continued treatment with
hydroxychloroquine.
ET AL.
Fourteen (60.9%) of our patients had achieved full clinical response
with hydroxychloroquine at time of chart review. Four patients failed
treatment (17.4%), with progression of hair loss, and evidence of on-
going disease activity after at least 7 months of treatment. All of these
patients were switched to an alternative agent. Two patients (8.7%)
had achieved full clinical response at a dose of 200 mg twice daily, but
demonstrated evidence of disease progression when reduced to
200 mg once daily. The dose of hydroxychloroquine was increased
again to 200 mg twice daily in both of these patients, and both were
well controlled on that dose at the time of chart review. These patients
were considered partial responders. The most common reason for
stopping hydroxychloroquine was because of full clinical response
(61.1% of patients who had stopped treatment at time of chart review,
n 5 11/18).
4 | DISCUSSION
LPP is the prototypical scarring alopecia and presents with patchy
irregular hair loss with perifollicular erythema and scale at the margins
of active lesions and absence of follicular ostia. Occasionally the hair
loss may be diffuse. Patients may report intense stinging, burning, pru-
ritus, and scalp tenderness. While the diagnosis may be suspected
based on clinical features, histological examination of a scalp biopsy is
required for confirmation. Early histological characteristics of LPP
include a dense lymphocytic infiltrate surrounding the infundibulum,
and isthmus with the lower portion of the hair follicle being spared.
Thereafter, an interface dermatitis occurs between the follicular epithe-
lium and the adjacent dermis. Sebaceous glands are also lost. The
inflammatory reaction eventually results in permanent destruction of
the hair follicle with extensive perifollicular lamellar fibrosis (Chiang
et al., 2010; Kang, Alzolibani, Otberg, & Shapiro, 2008).
LPP occurs more commonly in females than males, which is
reflected in our study with 92.6% of our patients being female. Peak
age of onset is between 30 and 60 years (Kang et al., 2008; Assouly &
Reygagne, 2009). Mean age at presentation in our patient cohort was
56.3 years overall, with a range between 23 and 77 years that corre-
sponds with previously published studies (Chiang et al., 2010; Cho
et al., 2010; Cevasco, Bergfeld, Remzi, & de Knott, 2007; Lyakhovitsky,
Amichai, Sizopoulou, & Barzilai, 2015). Of note, we found mean age at
presentation in males to be younger than females (42.5 and 57.4 years,
respectively). A younger mean age at presentation in males has previ-
ously been observed (Cho et al., 2010; Cevasco et al., 2007; Lyakhovit-
sky et al., 2015). Due to the small number of men in our study, it is
difficult to assess the statistical significance of these findings.
Effective treatment of LPP is notoriously difficult. No treatments
have been documented to be uniformly effective, and evidence is sub-
optimal. The first randomized controlled clinical trial evaluating a treat-
ment in LPP was only recently published. In it, mycophenolate mofetil
was compared with topical clobetasol lotion 0.05%. At the end of 6
months, both agents were found to be equally effective (Lajevardi
et al., 2015). None of the other agents used to treat LPP have been
evaluated in randomized controlled clinical trials.
NIC DHONNCHA ET AL.
As the underlying pathological process results in destruction of the
hair follicle and scarring, it is unlikely that any treatment will produce
hair regrowth in already scarred areas. Therefore, the goal of treatment
is to alleviate symptoms, and arrest or slow progression of hair loss
(Mirmirani, Wiley, & Price, 2003). Currently, no treatment protocols
exist for the management of LPP. Many systemic agents have been
used with limited success (Cevasco et al., 2007; Spencer, Hawryluk, &
English, 2009; Racz, Gho, Moorman, Noordhoek Hegt, & Neumann,
2013). Most studies published to date are difficult to interpret as they
are usually retrospective, subjective and not standardized, they lack
control groups, and have small numbers. Mid to high potency topical
corticosteroids are generally considered first-line therapy for LPP. Sys-
temic treatment options generally include antimalarial medications
(hydroxychloroquine), corticosteroids, tetracycline family antibiotics,
retinoids, ciclosporin, and mycophenolate mofetil. Oral corticosteroids
are usually reserved for aggressive, rapidly progressive disease, with
severe subjective symptoms. They may be used as a bridge therapy
until the chosen systemic agent shows effectiveness (Kang et al.,
2008). Oral retinoids, ciclosporin, and mycophenolate mofetil are pre-
dominantly reserved for refractory disease.
Hydroxychloroquine, the first-line systemic agent in our center for
treatment of LPP, is often preferred as the first-line systemic agent
because of its relatively good side-effect profile, but unfortunately
results are inconsistent.
Of our patients, 60.9% achieved full clinical response, and 8.7% of
patients achieved partial clinical response.
Chiang et al. (2010) reported a series of 40 patients with LPP
treated with hydroxychloroquine. They developed the LPP Activity
Index (LPPAI), which allows numeric scoring of the symptoms, signs,
activity, and spreading of the condition for statistical comparison and
showed that treatment with systemic hydroxychloroquine results in a
statistically significant improvement in the LPPAI. After 12 months, 83%
of patients were full or partial responders. Of nine patients considered
to be full responders, two-thirds (six patients) discontinued hydroxy-
chloroquine, and they all remained in remission for at least 1 year.
A single-center retrospective review by Lyakhovitsky et al. (2015)
reported 29 patients with LPP treated with hydroxychloroquine. Treat-
ment was combined with topical therapy in the majority of cases (22 of
25 patients). Full clinical remission was observed in 20% of patients,
with partial response in 64%. In responders, the onset of improvement
was noted after a mean time interval of 2.2 months.
Other studies have demonstrated less satisfactory results. Donati,
Assouly, Matard, Jouanique, and Reygagne (2011) reported disappoint-
ing results with progression of hair loss in all six of their patients with
LPP treated with hydroxychloroquine for a 6 month period. A further
case series of 22 patients with LPP treated with hydroxychloroquine,
found 41% of patients had a clinical improvement at follow-up
(Spencer et al., 2009).
Four of our patients experienced suspected adverse effects includ-
ing transient leucopenia and thrombocytopenia, urticaria, dyspnoea,
and dry eyes. Three of these patients stopped treatment themselves
without consulting a physician, and subjectively reported resolution of
| 3 of 4
suspected adverse effects on stopping treatment. Previously published
studies have shown hydroxychloroquine to be well tolerated. Some of
the reported side effects leading to cessation of therapy included head-
ache (Chiang et al., 2010), rash, and gastrointestinal symptoms (Lyakho-
vitsky et al., 2015). Another case series reported no adverse effects
(Samrao, Chew, & Price, 2010). Two patients in one study developed
facial hyperpigmentation that resolved on cessation of therapy (Lya-
khovitsky et al., 2015).
Four of our patients demonstrated evidence of disease progression
despite at least 7 months of treatment with oral hydroxychloroquine. All
of these patients were switched to an alternative agent. At time of chart
review, one of these patients had recently started on mycophenolate
mofetil following failure of treatment with hydroxychloroquine and sub-
sequently doxycycline. Two patients were on oral doxycycline, one hav-
ing failed treatment with hydroxychloroquine combined with mepacrine,
and the other having failed treatment with hydroxychloroquine and sub-
sequently mycophenolate mofetil. The last patient had decided to stop
all systemic medication shortly after the addition of mepacrine to
hydroxychloroquine, but denied any adverse effects.
The main limitations of our study include its retrospective nature
relying on review of case notes in a single center, small patients num-
bers, and lack of control or comparative group. No validated method
was used to assess disease severity or disease response to treatment,
and patient compliance with treatment was not assessed.
5 | CONCLUSION
Early diagnosis and treatment of LPP are essential in order to minimize
hair loss and disease progression. We report our experience of treating
patients with a clinicohistopathological diagnosis of LPP with oral
hydroxychloroquine. Our outcomes are similar to some of those previ-
ously published. A consistent, effective treatment for LPP remains elu-
sive. Further research and randomized controlled trials are required in
this area in order to improve the treatment and outcomes of this chal-
lenging disease.
CONFLIC T OF I NTE RE ST
None declared.
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How to cite this article: Nic Dhonncha E, Foley CC, Markham
T. The role of hydroxychloroquine in the treatment of lichen
planopilaris: A retrospective case series and review.
Dermatologic Therapy. 2017;30:e12463. https://doi.org/10.
1111/dth.12463