SKIN 
 

May 2020    Volume 4 Issue 3 
 

Copyright 2020 The National Society for Cutaneous Medicine 300 

SHORT COMMUNICATIONS 
 

 

Imiquimod-Induced Cutaneous Lupus-Like Reaction: A Potential Histologic 
Pitfall Highlighting the Importance of Clinicopathologic Correlation 
 
Brian J Simmons, MD1, M Shane Chapman, MD MBA1, Konstantinos Linos, MD2 

 
1Dartmouth-Hitchcock Medical Center, Section of Dermatology, Department of Surgery, Lebanon, NH 
2Dartmouth-Hitchcock Medical Center, Department of Pathology, Lebanon, NH 
 

 
 

Although controversial, the use of imiquimod 
for the treatment of primary melanoma in-situ 
(MIS) and residual MIS after surgical 
excisions has become more common. This is 
especially true in patients with multiple 
medical comorbidities, treatment of 
cosmetically sensitive areas and when 
surgical intervention would lead to significant 
functional impairment.1 Recognizing 
imiquimod-induced lupus-like reactions on 
histology is important and necessitates good 
clinicopathologic correlation given the 
potential ramifications of unnecessary 
laboratory workup and the need for systemic 
medications can be avoided. We report a 
case of lupus erythematous-like reaction in a 
patient being treated with imiquimod for 
residual MIS of the face. 
 
An 84-year-old woman with a history of 
multiple skin cancers and dementia was 
found to have an invasive melanoma of the 
right nasal side wall with a Breslow depth of 
2.3mm. The patient underwent wide local 
excision with 2cm margins, sentinel lymph 
node biopsy negative and repair with a full 
thickness graft. The final clinical staging of 
melanoma was IIA. However, margins were 
positive for MIS. The patient was 
subsequently treated with topical 0.1% 
tretinoin daily for two weeks followed by 
imiquimod 5% cream 5 days a week for 12 

weeks. Thereafter, the patient developed a 
pink erythematous patch with overlying scale 
(Figure 1). A scouting biopsy for residual MIS 
at the edge of the graft at 12 weeks showed 
a lichenoid interface dermatitis with features 
resembling a mixed connective tissue 
disease (Figure 2a & 2b) without residual 
MIS, which resolved after completion of 
topical imiquimod.  
 
Figure 1. Faint pink erythematous patch with 
overlying scale after 2-week pretreatment with 
tretinoin 0.1% cream and 12-week field treatment 
with imiquimod 5% cream. 

 
 



SKIN 
 

May 2020    Volume 4 Issue 3 
 

Copyright 2020 The National Society for Cutaneous Medicine 301 

Figure 2. (A) Vacuolar interface dermatitis with lichenoid infiltrate (10x, Hematoxylin and Eosin). (B) Scattered 
vacuolar interface with necrotic keratinocytes involving the dermoepidermal junction (20x, Hematoxylin and Eosin) 

 

Imiquimod is a toll-like receptor 7 agonist 
approved for superficial basal cell carcinoma, 
actinic keratosis and external genital warts. 
Common cutaneous reactions expected from 
treatment include erythema, pain, and 
erosions. In some instances, patients can 
have flu-like symptoms of fatigue and fever 
most pronounced when treating mucosal 
surfaces.  
 
On histologic examination, our patient’s 
imiquimod therapy induced a lupus-like 
interface reaction with adnexal vacuolar 
change, periadnexal lymphocytic infiltrates 
and colloid bodies that mimics cutaneous 
lupus.2 However, cutaneous lupus 
demonstrates dermal mucin deposition and 
increased thickness of the basement 
membrane, which distinguishes the two 
diagnoses on histologic examination. 
 
Overall, imiquimod is thought to induce lupus 
erythematous-like microscopic findings via 
local upregulation of interferon alpha and/or 
direct pro-apoptotic activity via B-cell 
lymphoma 2(Bcl-2) with subsequent 
activation of caspases.2  To date, there are 3 
cases in the literature addressing this 
phenomenon in patients aged 75 to 91 years 
old for the treatment of actinic keratosis and 
lentigo maligna.2,3 However, with better long 
term efficacy data the use of imiquimod for 

the treatment of residual MIS will continue to 
increase making the potential prevalence of 
a lupus-erythematous like reaction more 
common. Hence, this case highlights the 
importance of clinicopathologic correlation 
and good communication between the 
dermatologist and dermatopathologist to 
arrive at the correct diagnosis. 
 
Conflict of Interest Disclosures: None 
 
Funding: None 
 
Corresponding Author: 
M. Shane Chapman 
One Medical Center Dr. Lebanon, NH 03756 
Phone: (603) 650-3156 
Fax: (603) 650-3174 
Email: brian.j.simmons@hitchcock.org 

References: 
1. Park AJ, Paul J, Chapman MS, Samie FH. 

Long-Term Outcomes of Melanoma In Situ 
Treated With Topical 5% Imiquimod Cream: A 
Retrospective Review. Dermatol Surg. 
2017;43(8):1017-1022. 

2. Barr KL, Konia TH, Fung MA. Lupus 
erythematosus-like imiquimod reaction: a 
diagnostic pitfall. J Cutan Pathol. 
2011;38(4):346-350. 

3. Chan MP, Zimarowski MJ. Lupus 
erythematosus-like reaction in imiquimod-
treated skin: a report of 2 cases. Am J 
Dermatopathol. 2011;33(5):523-527. 

 

mailto:brian.j.simmons@hitchcock.org