Levothyroxine-associated lichenoid drug eruption: A case report
and review of levothyroxine-induced adverse reactions
Levothyroxine (LT4) is frequently used as thyroid
hormone replacement to treat hypothyroidism. Adverse skin reactions are
not common. Lichenoid drug eruption is a one such medication-related
reaction. the lesion morphology and pathology mimic lichen planus. The
current case describes a 47-year-old man who presented to us with a
diffuse levothyroxine-induced lichenoid drug eruption. The Naranjo
adverse drug reaction probability assessment score suggested this was
likely an ADR to levothyroxine. The eruption resolved after
discontinuation of the medication. We also reviewed the literature on
levothyroxine-associated adverse events.
Keywords: Lichenoid drug eruption, levothyroxine
1 | BACKGROUND
Thyroid hormone replacement is the first-line treatment of
hypothyroidism, and
levothyroxine
(LT4)
is the drug of choice. The basic principle is to convert exogenous
thyroxine (T4) into the active metabolite
tri-iodothyronine (T3) in peripheral
tissues.1 Long-term experience has proved its
strengths, including efficacy in alleviating symptoms, good compliance,
high intestinal absorption (70%–80%), long serum half-life (about 7
days), and low cost.2 Nevertheless, several adverse
reactions have been reported in the context of over-treatment with
levothyroxine, mainly involving the cardiovascular and locomotor
systems. Iatrogenic thyrotoxicosis may be characterized by atrial
fibrillation and
osteoporosis,
especially in older people and postmenopausal women.2
Adverse skin reactions to levothyroxine are rarely reported. Only a few
skin lesions have been reported to be induced by levothyroxine as
consequences of anaphylactic reactions, including pruritic rashes,
eczematiform skin eruptions, and lichenoid
eruptions.3-5 Cutaneous lichenoid or
lichen-planus-like eruptions may be induced by ingestion, contact or
inhalation of a variety of drugs and chemicals. It is similar to lichen
planus clinically and pathologically, with purple-red papules, obvious
scales and eczematous change. The lesions are extensive, invading both
trunk and limbs.6 There are many types of medications
that cause lichenoid drug eruptions, with antipyretic analgesics and
cardiovascular drugs being the most common.7Delayed-type hypersensitivity is considered to mediate the reaction.
In the present case report,
a
lichenoid drug eruption was found to be an adverse skin reaction of
levothyroxine. To the best of our knowledge, this is the first report of
such a reaction caused by a conventional dose of levothyroxine; there
has been a report that subacute lichenoid eruption due to L-thyroxine
overdosage.3
1.1 | Case presentation
A 47-year-old man with a history of hypothyroidism presented to the
emergency department with complaints of multiple scaly, erythematous
plaques over the extensor aspect
of limbs, back, scalp, and neck for a 2-month duration. His lesions were
non-painful, but itchy. On reviewing his drug history, it was found that
he had been received thyroid hormone substitutive therapy with
levothyroxine 50 μg daily for more than 2 months. Four months prior, a
similar lesion occurred after ingesting oral levothyroxine.
Cutaneous examination revealed multiple scaly, erythematous plaques on
the scalp (Figure 1A, B). There were generalized, confluent, scaly,
purplish erythematous plaques all over the body (Figure 1C, D). A biopsy
obtained from his back revealed epidermal hyperkeratosis accompanied by
focal keratosis, acanthotic cell layer thickening,
liquefaction degeneration of basal cells, a few dyskeratotic cells in
spinous layer, zonal dense lymphocytes, and few eosinophils in the
superficial dermis (Figure 2). These findings are actually consistent
with a diagnosis of lichenoid drug eruption. We then used the Naranjo
adverse drug reaction (ADR) probability scale8 to
assess the likelihood of lichenoid eruption being an ADR to
levothyroxine, and attained a total score of 7, which suggests a
‘probable ADR’ .
1.2 | Progression
At 2 months after withdrawal of the levothyroxine, the skin lesions
regressed without any treatment.
2 | DISCUSSION AND REVIEW
The most commonly seen adverse reactions
of
levothyroxine are symptoms of hyperthyroidism due to overtreatment,
including arrhythmias, dyspnea, and muscle weakness. Some less often
reported special adverse reactions are shown in Table 1. In cases of
adverse skin reactions, patch tests were all positive, suggesting the
involvement of delayed type hypersensitivity (DTH).3-5
As a biological substance, levothyroxine cannot be recognized by the
immune system as antigen. Nevertheless, lymphocytes of patients who had
taken levothyroxine were indeed sensitized to the
drug.16 Similarly, other biological medications
(insulin and heparin) are able to induce
hypersensitivity.17-18 Hence, the following hypotheses
are proposed: (1) levothyroxine serves as a hapten and combines with
carrier protein or adjuvants to become an antigen that recognized by
antigen-presenting cells; (2) the additives or excipients of tablets
causes the hypersensitivity rather than drug ingredient; (3) different
brands of preparations have differences in terms sensitization; or (4)
potential drug-induced immunologic responses of genetically susceptible
individuals may mediate an autoimmune mechanism.
In the case of lichenoid drug eruption, cessation of the offending drug
remains the mainstay treatment. Most authors believe that mild cases can
be managed with topical steroids and systemic anti-histamines. In severe
cases, administration of systemic corticosteroids is often required. In
our case, the eruption resolves after discontinuation of levothyroxine.
3 | CONCLUSION
This case report presents a rare adverse effect of levothyroxine.
Nevertheless, the detailed immunological and molecular mechanisms remain
unknown, and further clinical observation and research are need.