management of erosive lichen planus with topical tacrolimus and recurrence secondary to metoprolol
TRANSCRIPT
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© 2004 European Academy of Dermatology and Venereology
CASE REPOR T
JEADV
(2005)
19
, 236–239
DOI: 10.1111/j.1468-3083.2004.01116.x
Blackwell Publishing, Ltd.
Management of erosive lichen planus with topical tacrolimus and recurrence secondary to metoprolol
S Meyer, T Burgdorff, RM Szeimies, T Vogt, M Landthaler, S Karrer*
Department of Dermatology, University of Regensburg, 93042 Regensburg, Germany.
*
Corresponding author, Department of Dermatology, University of
Regensburg, D-93042 Regensburg, Germany, tel. +49 941 944 9656; fax +49 941 944 9657; E-mail: [email protected]
ABSTRACT
Metoprolol, a widely prescribed
β
-adrenergic receptor blocker, has occasionally been associated with adiversity of cutaneous reactions. We present a 79-year-old male patient with erosive lichen planus (LP) onthe feet and hands who was successfully treated with topical tacrolimus. Six months after the lesions hadbeen cured the patient received the
β
-receptor blocker metoprolol for the treatment of hypertonus. Withinonly 2 weeks of metoprolol intake the erosive lesions on the palms and feet recurred. After discontinuationof the drug and repetitive topical treatment with tacrolimus a complete remission of the lesions could beachieved. The recurrence of erosive LP probably secondary to metoprolol and the therapeutic success oftopical tacrolimus in the treatment of LP are discussed.
Key words:
cutaneous side-effects,
β
-receptor blockers, erosive lichen planus, FK506, tacrolimus
Received: 24 March 2004, accepted 20 April 2004
Introduction
Lichen planus (LP) is a chronic inflammatory dermatosis of
unknown aetiology. Theories of infectious (e.g. hepatitis
C, herpes simplex virus), autoimmune, metabolic or genetic
(HLA-Bw35, HLA-B8) causes have been proposed. T-cell-
mediated immunity seems to play a crucial part in the develop-
ment of LP, which is thought to represent an abnormal delayed
hypersensitivity reaction to as yet not identified specific antigens.
Clinically, non-erosive and erosive variants of LP have to be
distinguished. In particular, erosive LP of the genital or oral
mucosa or the skin represents a special therapeutic challenge
because of its frequent resistance to topical or systemic
therapies and high rates of recurrence.
Case report
A 79-year-old male patient presented with a 4-year history of
relapsing erosive skin lesions on the soles and toes of the feet
and palms resisting systemic retinoid treatment and psoralen
+ ultraviolet A-cream photochemotherapy. The diagnosis
of an acrodermatitis suppurativa Hallopeau was suspected,
therefore systemic treatment with methotrexate had been initi-
ated, but turned out to be ineffective. At that time the patient
did not take any drugs that may cause lichenoid drug eruptions.
Cutaneous examination revealed expansive inflammatory,
partly pustulous erosive lesions with peripheral oedema on
the palms and feet, predominantly on the soles (fig. 1a) and toes
showing permanent loss of some toenails. The erosions
were malodorous and particularly painful and burning. The
fingernails revealed pterygium-like alterations. The oral mucosa
was affected by sporadic superficial ulcers and a typical white
reticular pattern (Wickham phenomenon). Histopathologically,
compact orthohyperkeratosis, marked hypergranulosis, irregular
acanthosis and a band-like inflammatory cell infiltrate were
diagnostic for erosive LP. As the patient had not responded
to several other treatment modalities, including topical
corticosteroids, psoralen + ultraviolet A, methotrexate and reti-
noids, topical tacrolimus ointment 0.1% (Protopic®) was applied
twice daily on the soles and toes of the feet resulting in significant
improvement and almost complete resolution within 1 month
(fig. 1b).
Six months later, the patient received a
β
-receptor blocker
(metoprolol) for the treatment of hypertonus. After 2 weeks of
Management of erosive LP with topical tacrolimus
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oral intake of metoprolol the patient re-presented with a recur-
rence of erosive LP on the palms and feet. After discontinuation
of metoprolol, which may trigger lichenoid skin eruptions, the
erosive lesions resolved again within a few weeks of topical tac-
rolimus treatment.
Discussion
Erosive LP refers to eight different entities, including four
variants of mucosal erosive LP and four rare variants of
cutaneous erosive LP, i.e. erosive flexural LP and erosive LP of
fig. 1 Extensive erosive lesions on the sole (a) and complete resolution after 1 month of 0.1% topical tacrolimus ointment applied twice daily (b).
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Meyer
et al.
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the scalp, a linear IgA disease masquerading type and erosive LP
of the feet.
1
The latter represents a rare entity of the elderly,
which is characterized by chronic erosions of the sole(s) and the
permanent loss of the toenails.
2
These were the features also
present in the case reported here.
Although it is generally accepted that the pathogenesis of the
basal cell damage in LP primarily involves the cellular immune
response, the precise mechanisms are as yet unknown.
3
A wide
variety of drugs have been implicated in being potentially caus-
ative of this skin disorder. Drug-induced LP has been reported
for several drugs, including
β
-blockers, angiotensin-converting
enzyme inhibitors, methyldopa, penicillamine, quinidine and
many others.
4
Actually, it may be difficult to differentiate drug-
related LP from the idiopathic disorder; most evidence is based
on the dechallenge and rechallenge with the drug when these
data are available.
Cutaneous side-effects of
β
-receptor blockers are clinically
polymorphous. Atypical psoriasiform, LP-like, and eczematous
chronic rashes are mainly observed.
5
Apparently, cutaneous
side-effects of
β
-receptor blockers do mainly appear after sev-
eral months of continuous therapy and are rarely observed after
a few weeks of medication. In our patient presenting with a 4-
year history of erosive LP that had resolved after topical therapy
with tacrolimus, 14 days of metoprolol medication may have
triggered a recurrence of erosive LP, which did not differ from
the idiopathic disease as regards to morphology and localiza-
tion. To our knowledge the
β
-blocker metoprolol has not yet
been reported to induce erosive, ulcerative or bullous lichenoid
drug eruptions as described for propranolol and labetalol.
6,7
Pathogenetically, a delayed hypersensitivity reaction, and an
action on the epidermal chalone system (adrenalin-adenylcy-
clase-c-AMP-complex) may be assumed.
5
Manifesting with
erosive interdigital and plantar lesions the erosive LP represents
a rare, most symptomatic and debilitating variant of LP that is
frequently refractory to treatment.
8
Therapeutically, topically
applied corticosteroids, retinoids or cyclosporin as well as dif-
ferent systemic therapeutics, e.g. high-dose corticosteroids,
psoralen + ultraviolet A photochemotherapy, retinoids, griseo-
fulvin, antimalarials and thalidomide may be applied in
erosive LP.
8–11
However, the efficacy of these medications is
controversially discussed. In the patient presented here, very
good results were achieved with topically applied tacrolimus
(Protopic® ointment 0.1%). Tacrolimus (FK506) represents an
effective macrolide immunosuppressant originally introduced
for the prevention of allograft rejection of solid organ trans-
plants. Similar to cyclosporin, tacrolimus inhibits T-cell activa-
tion by initially binding to cytosolic FK-binding proteins,
which, in turn, interfere with the Ca
2+
/calmodulin-dependent
phosphatase calcineurin.
12
Ultimately, this results in the sup-
pression of cytokine gene transcription with interleukins 2, 4
and 5 being mainly affected.
13
Topical tacrolimus was shown to
be effective in the treatment of atopic and contact dermatitis
and other inflammatory skin diseases such as steroid-induced
rosacea, cutaneous sarcoidosis and psoriasis.
14–17
In the recent
literature, successful treatment and management of oral LP
with topical tacrolimus has been reported in several cases and
studies.
18,19
In contrast to the systemic therapy options men-
tioned above, topical tacrolimus is comparatively low in side-
effects, safe and effective. According to the present data, topical
tacrolimus seems to be a promising immunomodulatory agent
in the treatment of erosive LP, which is often resistant to local
steroid therapy. Despite this new therapeutic approach of ero-
sive LP, dermatologists should be aware of possible lichenoid
drug reactions secondary to the use of
β
-adrenoceptor blocking
agents. In case of cutaneous side-effects,
β
-blocker medication
should be discontinued prior to recommending any other ther-
apeutic strategy.
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