BJD

R E V I E W A RT I C L E British Journal of Dermatology

A comprehensive review of current treatments for

granulomatous cheilitis
T. Banks MD and S. Gada MD
Walter Reed National Military Medical Center, 8901 Rockville Pike, Bethesda, MD 20889-5600, U.S.A.

Summary

Correspondence Granulomatous cheilitis (GC) is a poorly understood disease process belonging to

Taylor Banks. the larger group of orofacial granulomatosis. The treatment of GC has proven
E-mail: taylor.banks@med.navy.mil exceedingly difficult. While various treatments have been applied to GC, there
has been no uniform or predictably successful model demonstrated in the litera-
Accepted for publication
7 December 2011
ture. Poor understanding of the aetiological mechanisms underpinning GC has
significantly hampered the development of an effective approach to treatment.
Funding sources Those therapies that have shown promise principally consist of agents with anti-
None. inflammatory activity such as corticosteroids and immunomodulatory medica-
tions. On a careful review of the literature, we have found no systematic review
Conflicts of interest
and assessment of current treatments. We seek to address this absence in the
None declared.
available literature by providing a consolidated overview of current treatment for
DOI 10.1111/j.1365-2133.2011.10794.x GC.

Granulomatous cheilitis (GC) is a poorly understood disease
process belonging to the larger group of orofacial granuloma-
tosis. It was first described by Miescher in 1945 and consists
of initially episodic but eventually persistent, painless swelling
of one or both lips.1,2 The median age at presentation is 25–
28 years with nearly equal sex distribution.2 Histologically,
the condition is characterized by noncaseating granulomas,
oedema, lymphangiectasia, and a perivascular lymphocytic
infiltrate.3,4
Granulomatous cheilitis shares characteristics with and is as-
sociated with several conditions (Table 1). Chief among these
is the Melkersson–Rosenthal syndrome, a triad of swelling of
the lip, facial nerve paralysis and fissured or furrowed ton-
gue.5 Additionally sarcoidosis, infectious processes such as
tuberculosis, and Crohn disease are included in this group.1 It
has been suggested that up to 0Æ5% of patients with Crohn
disease will develop GC and its presence either prior to or
accompanying initial gastrointestinal manifestations of Crohn
disease has been noted.4,6,7 Although the underlying mecha-
nisms that cause GC remain unclear, it has been suggested that
it probably consists of a polyaetiological interplay of environ-
mental exposures and genetic predisposition.1
The treatment of GC has proven exceedingly difficult. While
various treatments have been applied to GC, there has been no
uniform or predictably successful model demonstrated in the
literature. Numerous modalities used in the past have proven
unsuccessful, including chloroquine, sulfa drugs, tetracycline,
antihistamines, isoniazid, and repeated irradiation.3,8 Of those
treatments documented in a variety of case reports and small
case series, there have been no comparative trials.9 Similarly,
on a careful review of the literature, we have found no sys-
tematic review and assessment of current treatments. We seek
to address this absence in the available literature by providing
a consolidated overview of current treatment for GC
(Table 2).
Corticosteroids
Used both in the form of local injection and systemically, cor-
ticosteroids have remained a consistent mainstay of many GC
treatment regimens. Whether as sole treatment or an adjunct
to other medical or surgical options, corticosteroids have been
employed as a potent agent in decreasing the inflammation
evident on histological examination of patients with GC.10,11
While oral prednisone has been used as systemic treatment,
intralesional use of triamcinolone has been the predominant
form of corticosteroid treatment in more recent case
reports.10–12 Although oral doses are not well established, int-
ralesional triamcinolone dosing varies from 10 to 20 mg doses
with intervals from weeks to months between injections.13,14
Although success has been noted with such use, it is often
temporary and no large studies exist examining the long-term
efficacy of corticosteroids in GC.
Clofazimine
Clofazimine is a medication derived from phenazine dye,
which has also been used in the treatment of leprosy, pyo-
derma gangrenosum and discoid lupus erythematosus.15 First
used in a case series by Podmore and Burrows15 in 1986, this

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934 BJD  2011 British Association of Dermatologists 2012 166, pp934–937
 Current treatments for granulomatous cheilitis, T. Banks and S. Gada 935

Table 1 Conditions associated with or in the differential diagnosis of
granulomatous cheilitis
Melkersson–Rosenthal syndrome
Crohn disease
Sarcoidosis
Chronic granulomatous disease
Primary syphilis
Tuberculosis
Leprosy
medication has been reported to be an effective treatment for
GC.16,17 It has been used in doses ranging from 100 to
300 mg per dose in both daily and every other day dosing
regimens.16 Through its antibacterial, anti-inflammatory and
immunomodulatory effects, clofazimine’s broad spectrum of
action speaks to the equally nebulous character of GC’s under-
lying aetiology. The principle side-effect is a dose-related, red-
brown pigmentation of the skin, with gastrointestinal upset
and rarely hepatotoxicity also reported.15,16
Antibiotics
As noted previously, several antibiotics including sulfa drugs,
tetracycline and isoniazid have been used unsuccessfully in the
past; however, recent reports indicate a continued use for
antibiotic agents. No infectious agent has been clearly linked
with GC and it is probably the associated anti-inflammatory
activity and modulation of the ongoing immune reaction that
is responsible for the effect of these drugs.18,19 Among the
antibiotics that have gained more recent prominence are mi-
nocycline (100 mg daily) and roxithromycin (150–300 mg
daily), which belong to the tetracycline and macrolide classes,
respectively.18–20 Further attention has been garnered by met-
ronidazole, particularly given the association of GC with Cro-
hn disease noted in much of the literature.13,21,22 Mixed but
promising results have been obtained in the treatment of GC
with metronidazole using doses of 750–1000 mg daily.10,21,23
Other immunomodulators
A few case reports document successful use of a variety of
other immunomodulatory agents. Infliximab, a chimeric
monoclonal antibody that targets tumour necrosis factor
(TNF)-a and has been effective in the treatment of Crohn dis-
ease, has also been touted as a promising agent for use in GC
in infusion doses ranging from 3 to 5 mg ⁄kg.22,24 Similarly,
in a case report by Thomas et al.,25 thalidomide was success-
fully used in a patient with GC in doses of 100 mg daily
which were decreased to every other day. Thalidomide also
demonstrates TNF-a inhibitory action, which may explain its
effectiveness.25 Although these agents and the targeting of
TNF-a represent a promising avenue for future treatment,
their long-term safety and efficacy remains to be seen in
addressing GC.
A few studies have examined the use of disease-modifying
agents known to reduce the proliferation of immune cell lines.
Among these studies are several case reports on the use of
methotrexate.26,27 The doses for such treatments range from 5
to 10 mg of oral methotrexate administered weekly. Interest-
ingly, a case report by Tonkovic-Capin et al.26 addresses the
use of methotrexate in a patient with Crohn disease and GC,
leading the authors to comment on the potential utility of
periodically searching for underlying Crohn disease in patients
with GC. Another form of treatment offering antiproliferative
effects on immune cells are the fumaric acid esters such as
Fumaderm (Biogen Idec, Weston, MA, U.S.A.). These medi-

Table 2 Medications used in the treatment of

granulomatous cheilitis Medication Case report or study Dose
10
Triamcinolone Coskun et al. 10–20 mg per dose (intralesional)
Eisenbud et al.11 with weeks to months between doses
Perez-Calderon et al.12
Clofazimine Podmore and Burrows15 100–300 mg daily or every other day
Fernandez Freire et al.16
Minocycline Veller Fornasa et al.19 100 mg daily
Roxithromycin Ishiguro et al.18 150–300 mg daily
Inui et al.20
Metronidazole Coskun et al.10 750–1000 mg daily
Miralles et al.21
Kano et al.23
Infliximab Ratzinger et al.22 3–5 mg ⁄ kg per infusion
Barry et al.24
Thalidomide Thomas et al.25 100 mg daily to every other day
Methotrexate Tonkovic-Capin et al.26 5–10 mg administered orally on
Leicht et al.27 a weekly basis
Fumaric acid esters Kleine et al.28 120–720 mg daily
(Fumaderm) Breuer et al.29
Tranilast Chiba et al.31 200–400 mg daily

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BJD  2011 British Association of Dermatologists 2012 166, pp934–937
936 Current treatments for granulomatous cheilitis, T. Banks and S. Gada
cations have found use in the treatment of psoriasis and two
case reports indicate possible benefit in the treatment of GC
using doses of 120–720 mg daily.28,29
Finally, tranilast, a medication used in the treatment of sar-
coidosis and also in allergy-driven disease processes due to its
inhibition of chemical mediator release from mast cells, has
been used in the management of GC.30 Chiba et al. 31 pre-
sented two cases in which the medications tranilast and ketoti-
fin were used in prolonged courses in doses of 200–400 mg
daily and 2 mg daily, respectively.
Surgical management
Surgical management through cheiloplasty is frequently dis-
cussed in the literature as an option reserved for severe or
deforming GC.32,33 The removal of tissue from the affected
lip(s) can be effective in restoring function and cosmetic
appearance, providing an added benefit in addressing the
social impairment felt by many patients with GC.32 Another
reported procedure, while not surgical, is the use of helium-
neon laser radiation treatment. Bugay and Lialina published
the results of 83 patients who underwent this treatment,
which was reported to provide significant benefit particularly
to those with disease duration of less than 4 years.34 The ben-
efits of surgery and other procedural options must be weighed
against side-effects such as loss of normal sensation in the af-
fected lip(s) and of recurrence despite surgery. In effect, sur-
gery should remain as an option only for those patients who
are severely affected or who have impairment of function due
to GC.14
Conclusion
GC is a chronic and potentially disfiguring disease process
whose unknown origin has hindered the development of
effective treatment regimens. Affording some promise, the
association between GC and Crohn disease has been noted
widely in the available literature, as has a shared effective-
ness for some of the treatment modalities used to treat Cro-
hn disease. While agents that address the inflammatory
response have been demonstrated to provide benefit to
patients, evidence in the literature remains restricted to case
reports with no larger studies available. Although surgical
management remains an option for those severely affected
patients, it does not represent a definitive cure and contin-
ued investigation of medical options should be pursued.
What’s already known about this topic?
• Various treatment regimens have been employed in
addressing granulomatous cheilitis; however, no single
therapy has emerged as a leading intervention.
• The literature consists of case reports and series with no
overarching summary of treatments.
BJD  2011 British Association of Dermatologists 2012 166, pp934–937
What does this study add?
• Our paper uniquely provides a concise but extensive
overview of the various treatment regimens used in the
hope of guiding future research and treatment for this
rare and poorly understood disease process.
Acknowledgments
The authors express their sincere thanks to Mr William Wick-
ham and Ms Sonia Galiber for their assistance in translating
several sources for use in this paper. The authors would also
like to thank Dr. Susan Laubach for her assistance in preparing
this manuscript.
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