Answer
Rash secondary to erlotinib (epidermal growth factor inhibitor): Given the patient's history and the physical findings of an acneiform rash, an erlotinib-induced rash was diagnosed. Erlotinib is an epidermal growth factor receptor (EGFR) inhibitor, a class of drug that includes cetuximab and gefitinib. This reaction is typically not associated with symptoms such as fever, myalgia, or arthralgia and occurs in 55-78% of patients taking EGFR inhibitor. The rash is often on the face (82% of patients), shoulders, and trunk (64%). The eruption always spares the palmar surfaces.
The pathology of erlotinib-induced rash involves a dense monomorphic infiltrate of neutrophils that cause a florid, suppurative folliculitis. Advanced lesions lead to the destruction of follicles, with perifollicular granuloma formation, dermal edema, and vasodilation with progression, which is often dose dependent. Treatment includes stopping the medication and providing supportive dermatologic care.
The differential diagnosis of skin lesions in a patient with a history of clear-cell RCC currently undergoing chemotherapy includes not only a drug-induced rash, as in the case, but also the possibility of relatively severe forms of the drug-induced rash, namely, Stevens-Johnson syndrome (SJS). Other considerations are fungal infection, reactivated herpes zoster (shingles), and, in rare cases, a manifestation of RCC metastasizing to the skin.
Patients with a reactivation of herpes zoster (shingles) infection typically have a prodrome of fever, malaise, and headache that precedes the vesicular dermatomal eruption by several days. In addition, their chief complaint is often pain, which is frequently described as a deep, burning sensation. The condition is usually limited to one dermatome in an otherwise healthy host, but it can also involve several dermatomes or progress to systemic involvement in immunocompromised individuals.
Drug-induced SJS is an immunocomplex-mediated hypersensitivity reaction that is a severe expression of erythema multiforme (also referred to as erythema multiforme major). This reaction usually begins 1-3 weeks after the causative agent is first taken. The condition is often accompanied by a prodrome of fever and flulike symptoms, followed by the appearance of a typically nonpruritic rash characterized by poorly defined macules with purpuric centers. The lesions are usually symmetrically distributed on the face and the trunk, with the scalp often spared. The rash usually progresses from the initial macules to blisters and can eventually lead to extensive epidermal detachment. The skin lesions are painful and associated with edema, skin necrosis, and erosions of the mucous membranes. Specific drugs implicated in the development of SJS include penicillins and sulfa antibiotics, barbiturates, and anticonvulsants (eg, phenytoin, carbamazepine, valproic acid, lamotrigine).
The prevalence of cutaneous metastases due to clear-cell RCC is approximately 3%. The most common presentation is a macular rash or urticaria. The diagnosis is confirmed with biopsy. Patients with cutaneous metastases have often a short disease-specific survival of several months. Overall, cutaneous metastases from carcinomas are relatively uncommon. The breast, stomach, lung, uterus, large intestine, and kidneys the organs that most frequently produce cutaneous metastases.
This patient's lesions resolved over 3 weeks with supportive treatment. EGFR inhibitor is now approved for use in patients with colon cancer, lung cancer, or head and neck cancer. Because this drug is increasingly used, this specific drug reaction is important to recognize, and, in general, clinicians must be aware of drug-induced adverse effects, specifically skin manifestations.
For more information on drug rashes, see the eMedicine article Drug Eruptions (within the Dermatology specialty).
References - Chan HL, Stern RS, Ardt KA, et al. The incidence of erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis. A population based study with particular reference to reactions caused by drugs among outpatients. Arch Dermatol 1990;126;43-77.
- Jacot W, Bessis D, Jorda E et al. Acneiform eruption induced by epidermal growth factor receptor Inhibitors in patients with solid tumors. Br J Dermatol 2004;151:238-41.
- Mueller TJ, Hong W, Greenberg E, et al. Cutaneous metastases from genitourinary malignancies. Urology 2004;63:1021-6.
- Schmader K. Herpes zoster in older adults. Clin Infect Dis 2001;32:1481-6.
- Van Doorn R, Kirtschig G, Scheffer E, et al. Follicular and epidermal alterations in patients treated with (ZD1839) Iressa, an inhibitor of the epidermal growth factor receptor. Br J Dermatol 2002;147:598-601.
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BACKGROUND
A 69-year-old woman with metastatic clear-cell renal cell carcinoma (RCC) presents with a maculopustular, acne-like rash on her scalp, face, and posterior aspect of her trunk. The rash has lasted 9 days. The patient's history is significant for treatment with erlotinib, an epidermal growth factor inhibitor, which was started approximately 2 weeks ago to treat persistent growth of a metastatic lesion in her pancreas despite therapy with bevacizumab, a vascular endothelial factor inhibitor. Surgical resection for kidney cancer was attempted several years ago.
Over the past few days, the rash has become pustular with notable crusting. Treatment with a topical antibiotic cream and an oral antibiotic has proved ineffective. The rash has spread to the back and is now involving an increasing area of the scalp (see Images).
What is the diagnosis?
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Hint
A drug-induced condition
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Author:
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Joyce M. Siler, RN , Oncology Nurse, Mayo Clinic, Jacksonville, Fla
Winston W. Tan, MD, FACP, Assistant Professor of Medicine, Division of Hematology/Oncology, Mayo Clinic College of Medicine, Jacksonville, Fla
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eMedicine Editor:
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Rick G. Kulkarni, MD, Assistant Professor, Yale School of Medicine, Section of Emergency Medicine, Department of Surgery, Attending Physician, Medical Director, Department of Emergency Services, Yale-New Haven Hospital, Conn
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