Baylor University Medical Center Proceedings July 2017 - 333

Acute exacerbation of myasthenia gravis with topical
imiquimod use
Saadeddine Saad, BS, Bobbak Mansouri, MD, and Chad Housewright, MD

Imiquimod activates the immune system when applied to a local area. We
report a patient with a history of well-controlled myasthenia gravis who was
prescribed imiquimod for lentigo maligna. Treatment was halted after 2 weeks
when the patient reported itching and irritating sensations in his throat, consistent with previous myasthenia exacerbations. The symptoms improved
once imiquimod use was discontinued. We advise clinicians to be cautious
when prescribing imiquimod to a patient with a history of myasthenia gravis.

miquimod is an immune response modiﬁer used as a topical therapy for a variety of skin conditions, including actinic
keratoses, superﬁcial basal cell carcinomas, and viral infections such as condyloma (1). It has several other documented
oﬀ-label dermatologic uses, including Kaposi's sarcoma, scar
management, and lentigo maligna (2). Myasthenia gravis (MG)
is an autoimmune disorder that targets acetylcholine receptors
at the neuromuscular junction, resulting in varying degrees of
muscle weakness (3). Common presenting symptoms of MG
include manifestations of ocular muscle weakness (ptosis and
diplopia) and bulbar weakness (dysarthria and dysphagia). Bulbar
muscle weakness can eventually spread to include the muscles of
respiration, leading to life-threatening respiratory collapse. We
describe a patient with MG with an exacerbation of his symptoms
secondary to topical imiquimod use for a lentigo maligna.
CASE DESCRIPTION
A 72-year-old white man with a history of MG controlled with
pyridostigmine and azathioprine presented with a brown patch on
his left nasal ala measuring 2.0 cm × 1.5 cm. A biopsy revealed
melanoma in situ, lentigo maligna type. Due to the size and location of the lesion, he opted for imiquimod 5% cream applied once
daily for 8 to 12 weeks to reduce the lesion's size prior to surgical
excision. Following 2 weeks of imiquimod use, the patient reported
an itching and irritating sensation in his throat, similar to that of
his typical MG exacerbations. The patient discontinued the use of
topical imiquimod immediately. Three weeks later, he reported a
return to his baseline status with regards to MG symptoms.
DISCUSSION
This case represents the second report of MG exacerbation
with topical imiquimod use. Wolfe et al described an 80-year-old
Proc (Bayl Univ Med Cent) 2017;30(3):333

woman with MG controlled without medication who was
treated with topical imiquimod for multiple squamous cell
carcinomas of the legs (4). She experienced a resurgence of
her MG symptoms, which included diﬃculty chewing, mild
diplopia, dysphagia, dysphonia, and facial muscle weakness
within 1 week of imiquimod initiation. Her symptoms resolved
with pyridostigmine use during the course of her imiquimod
therapy. In contrast, our patient was already on longstanding
immunosuppressive therapy and used imiquimod on a much
smaller surface area. Yet, he still experienced an exacerbation of
MG symptoms after only 2 weeks of use. Similarly, our patient's
symptoms resolved after discontinuation of topical imiquimod.
Although the exact mechanism of action is unknown, imiquimod is a toll-like receptor-7 agonist that triggers activation of the
immune system (5). This activation leads to the production of
various interleukins, interferon-gamma, and tissue necrosis factoralpha, all of which contribute to an immune-mediated response
(5). The immune response can lead to increased production of
immunoglobulins. This immunoglobulin production leads to a
chronic autoimmune state, which may present with varying levels
of muscle weakness. Based on these ﬁndings, and considering the
increasing use of topical imiquimod, clinicians should proceed
with caution when prescribing topical imiquimod to patients with
MG, as the severity of these adverse eﬀects has not been well documented. Patients should be counseled on these possible adverse
eﬀects and should discontinue use of the medication immediately
if they have any symptomatic manifestations of their disease.
1.
2.
3.
4.
5.

AldaraTM [package insert]. 3M Health Care Limited, October 2010.
David CV, Nguyen H, Goldenberg G. Imiquimod: a review of oﬀ-label
clinical applications. J Drugs Dermatol 2011;10(11):1300-1306.
Gwathmey KG, Burns TM. Myasthenia gravis. Semin Neurol 2015;35(4):
327-339.
Wolfe CM, Tafuri N, Hatﬁeld K. Exacerbation of myasthenia gravis during
imiquimod treatment. J Drugs Dermatol 2007;6(7):745-746.
Schön MP, Schön M. Imiquimod: mode of action. Br J Dermatol
2007;157(Suppl 2):8-13.

From Texas A&M College of Medicine Health Science Center (Saad, Mansouri,
Housewright) and the Department of Dermatology, Scott and White Hospital
(Mansouri, Housewright), Temple, Texas.
Corresponding author: Chad Housewright, MD, Department of Dermatology,
Scott and White Hospital, 409 W Adams Avenue, Temple, TX 76501 (e-mail:
chad.housewright@bswhealth.org).
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