A Case of Severe Skin Adverse Reactions Caused by Cetuximab

Summary

This case report describes severe cetuximab-induced skin toxicity in a rectal cancer patient, outlining diagnosis, management, and recovery. The paper provides a reproducible protocol, including dermatologic evaluation, biopsy, immunosuppressive therapy, and follow-up, demonstrating successful treatment and transition to alternative chemotherapy.

Abstract

Cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor (EGFR), is associated with various adverse reactions, among which skin-related adverse events (AEs) are common. This case report details a patient who developed severe skin AEs after cetuximab administration and outlines a reproducible management protocol. The patient, a 44-year-old man with KRAS wild-type metastatic rectal cancer, was undergoing cetuximab-based chemotherapy. Approximately 10 days after initiating a cetuximab monotherapy cycle following prior combination regimens, he developed severe Grade 3-4 acneiform rash and erythema multiforme-like lesions with ulceration, exudation, crusting, scaling, and hyperpigmentation on the face and anterior chest. Evaluation included physical examination, dermatology consultation, skin biopsy for histopathology and direct immunofluorescence, and laboratory tests (including serum IgE, eosinophil count, C-reactive protein, HLA-A*31:01 genotyping, viral serologies, and bacterial cultures). Management involved permanent discontinuation of cetuximab, high-dose intravenous methylprednisolone (1.5 mg∙kg^-1∙day^-1), cyclosporine (3 mg∙kg^-1∙day^-1), supportive wound care in a burn unit, and topical ocular/oral care. Symptoms improved significantly within 72 h, with a 90% reduction in lesion severity by day 14. Therapy was successfully transitioned to bevacizumab plus FOLFOX after dermatologic recovery, with no rash recurrence during follow-up. This case highlights the importance of early recognition, multidisciplinary management, and protocol-driven intervention for severe cetuximab-induced skin toxicity to ensure patient safety and treatment continuity.

Introduction

Cetuximab, a chimeric immunoglobulin G1 monoclonal antibody, has significantly advanced the treatment landscape for several malignancies, particularly metastatic colorectal cancer (mCRC) and head and neck cancers, especially those with RAS wild-type status¹. By specifically targeting the epidermal growth factor receptor (EGFR), it inhibits ligand-induced receptor phosphorylation, thereby curbing downstream signaling pathways involved in tumor cell proliferation, angiogenesis, and metastasis^2,3.

Despite its therapeutic efficacy, cetuximab treatment is frequent....

Protocol

Prior to the collection of clinical data (including but not limited to medical history, laboratory test results, and imaging findings) and the acquisition of skin lesion photographs (Figure 3), the participant was provided with a detailed informed consent form that explicitly stated the purpose, scope, and manner of using his personal medical information and images (i.e., for academic research, manuscript publication in peer-reviewed journals, and non-commercial academic communication). The form clearly distinguished between "de-identified data/image use" (all personal identifiers, such as name, hospital ID, and facial features in....

Results

The patient's baseline CTCAE v5.0 skin toxicity score was 0 before the reaction onset. The severe cutaneous adverse reaction manifested acutely 10 days post cetuximab infusion (cycle 14). Key findings included:

Development of Grade 3 acneiform rash and erythema multiforme-like lesions, progressing to diffuse desquamation and erosive lesions involving >30% of BSA

Discussion

This case illustrates a severe SCAR likely induced by cetuximab monotherapy, successfully managed using a structured multidisciplinary protocol. Cetuximab inhibits EGFR signaling, leading to impaired keratinocyte differentiation, increased apoptosis, abnormal keratin secretion, and subsequent release of pro-inflammatory mediators (e.g., cytokines, chemokines), provoking intense local inflammation and acneiform rashes^{1,3,5,<.......}

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
10% neutral buffered formalin	Sigma-Aldrich	#HT501128	Used for fixation of skin biopsy specimens (24 h at room temperature); equivalent neutral buffered formalin products from other manufacturers are acceptable
Canon EOS Rebel T7i	Canon Inc.		Digital camera; used for standardized photographic documentation of skin lesions (consistent lighting, white background, and 1 cm scale reference); any digital camera with ≥24.1 megapixels and manual exposure mode is suitable
Cobas 8000	Roche Diagnostics		Standard automated analyzer; used for complete blood count (CBC), liver function tests (LFTs), renal function tests (RFTs), and C-reactive protein (CRP) detection; other clinical-grade automated analyzers meeting ISO 15189 standards can be substituted
eosin	Sigma-Aldrich	#HT110232	Used for counterstaining of paraffin-embedded skin sections; compatible with hematoxylin #HHS32; equivalent eosin solutions (0.5%–1% concentration) from other suppliers are applicable
FITC-Conjugated Anti-Human C3 Antibody	Agilent	#ZA004	Used for DIF detection in skin biopsy specimens; dilution: 1:40 in PBS; specificity: human complement C3; other FITC-conjugated anti-human C3 antibodies with validated reactivity are applicable
FITC-Conjugated Anti-Human Fibrinogen Antibody	Agilent	#ZA005	Used for DIF detection in skin biopsy specimens; dilution: 1:50 in PBS; specificity: human fibrinogen; equivalent antibodies from other brands (e.g., Dako) can be used if they meet DIF experimental requirements
FITC-Conjugated Anti-Human IgA Antibody	Agilent	#ZA002	Used for DIF detection in skin biopsy specimens; dilution: 1:30 in PBS; specificity: human IgA; other FITC-conjugated anti-human IgA antibodies with cross-adsorption to avoid species interference are acceptable
FITC-Conjugated Anti-Human IgG Antibody	Agilent	#ZA001	Used for direct immunofluorescence (DIF) detection in skin biopsy specimens; dilution: 1:20 in PBS; specificity: human IgG; equivalent FITC-conjugated anti-human IgG antibodies from other brands (e.g., Jackson ImmunoResearch) are suitable
FITC-Conjugated Anti-Human IgM Antibody	Agilent	#ZA003	Used for DIF detection in skin biopsy specimens; dilution: 1:25 in PBS; specificity: human IgM; equivalent antibodies from other suppliers (e.g., Abcam) meeting DIF-grade standards can be substituted
hematoxylin	Sigma-Aldrich	#HHS32	Used for nuclear staining of paraffin-embedded skin sections; compatible with eosin #HT110232; Mayer's or Harris' hematoxylin solutions from other manufacturers are acceptable
HHV-6 IgG IFA Kit	Zeus Scientific	#Z-2200	Used for detection of human herpesvirus-6 (HHV-6) IgG antibodies; indirect immunofluorescence assay; positive control: HHV-6-infected T cells; equivalent IFA kits from other suppliers are suitable
HLA-A*31:01 Genotyping Kit	Thermo Fisher Scientific	#4488393	Used for PCR-based sequence-specific oligonucleotide probing (SSOP) of HLA-A31:01 allele; includes primers, probes, and reaction buffers; other FDA-approved HLA-A31:01 genotyping kits with equivalent accuracy can be substituted
HSV IgM/IgG ELISA Kit	Siemens Healthineers	#09606790	Used for detection of herpes simplex virus (HSV) IgM and IgG antibodies; sensitivity: ≥98%, specificity: ≥97%; other ELISA kits meeting CE IVDR standards are acceptable
ImmunoCAP, Phadia, Thermo Fisher Scientific	Phadia (Thermo Fisher Scientific)		Used for quantification of serum IgE; detects total IgE concentration (detection range: 0.1–5000 IU/mL); other certified immunoassay kits with equivalent sensitivity and specificity can be used
Nikon Eclipse Ni-U	Nikon Instruments		Fluorescence microscope; used for observation of direct immunofluorescence (DIF) slides; equipped with FITC filter (excitation wavelength: 490 nm, emission wavelength: 525 nm); any fluorescence microscope with ≥1000× magnification and FITC-compatible filters is suitable
optimal cutting temperature (OCT) compound	Tissue-Tek	#4583	Used for snap-freezing of skin biopsy specimens (stored at -80 °C); ensures tissue integrity during cryosectioning; equivalent OCT compounds from other brands (e.g., Sakura Finetek) are acceptable
Pain relief pump system	REHN(I)/REHH(11)-256	C14230120200002117850000005	Sterile, disposable; used for postoperative pain management; complies with ISO 13485 medical device standards; other sterile disposable pain relief pump systems with the same flow rate (2 mL/h) are applicable
Pre flushing syringe	Bidi Medical Equipment (Shanghai) Co., Ltd	C14281803900001071870000016	Sterile; used for pre-flushing of intravenous catheters; volume: 10 mL; other sterile syringes meeting GB 15810-2019 (China) or ISO 7886-1 standards can be substituted
Primary Antibody: Anti-HER2 (rabbit monoclonal)	Dako	#4B5	Used for IHC detection of HER2 protein in colorectal cancer tissue; dilution: 1:100; positive control: HER2-positive breast cancer tissue; equivalent anti-HER2 antibodies (clone: SP3) from other suppliers are acceptable
Primary Antibody: Anti-Ki-67 (mouse monoclonal)	Dako	#MIB-1	Used for IHC detection of Ki-67 proliferation index in colorectal cancer tissue; dilution: 1:200; positive control: tonsil tissue; other anti-Ki-67 antibodies (clone: MM1) with validated sensitivity can be substituted
Primary Antibody: Anti-MLH1 (mouse monoclonal)	Dako	#M7359	Used for immunohistochemistry (IHC) detection of MLH1 protein in colorectal cancer tissue; dilution: 1:100; specificity verified by positive control (normal colorectal mucosa); equivalent anti-MLH1 antibodies (clone: ES05) from other suppliers are acceptable
Primary Antibody: Anti-MSH2 (mouse monoclonal)	Dako	#M7324	Used for IHC detection of MSH2 protein in colorectal cancer tissue; dilution: 1:200; positive control: normal colorectal mucosa; equivalent anti-MSH2 antibodies (clone: FE11) from other brands are suitable
Primary Antibody: Anti-MSH6 (mouse monoclonal)	Dako	#M7457	Used for IHC detection of MSH6 protein in colorectal cancer tissue; dilution: 1:150; positive control: normal colorectal mucosa; other anti-MSH6 antibodies (clone: EP49) with validated specificity can be substituted
Primary Antibody: Anti-PMS2 (mouse monoclonal)	Dako	#M7437	Used for IHC detection of PMS2 protein in colorectal cancer tissue; dilution: 1:50; positive control: normal colorectal mucosa; equivalent anti-PMS2 antibodies (clone: A16-4) from other manufacturers are applicable