Minocycline-Induced Hyperpigmentation in a Patient Treated with Erlotinib for Non-Small Cell Lung Adenocarcinoma

Abstract

Introduction: While epidermal growth factor receptor (EGFR) inhibitors have improved progression-free survival in patients with non-small cell lung cancer (NSCLC), one of the most common adverse effects is papulopustular skin eruption, which is frequently severe enough to be treated with oral minocycline or doxycycline. Case: We present a case of an 87-year-old man who developed a severe papulopustular skin eruption secondary to erlotinib therapy for NSCLC. Control of the eruption with 100 mg of minocycline twice daily for 8 months eventually led to blue-gray skin hyperpigmentation. After 30 months, this side effect was recognized as minocycline drug deposition, which was confirmed with skin biopsy. Discussion: Compliance with EGFR inhibitor therapy in NSCLC is often challenging due to common side effects, most notably cutaneous skin eruptions. Treatment of cutaneous toxicities is important to preserve patient compliance with targeted cancer therapy. Use of minocycline to treat the most common cutaneous side effect (papulopustular eruption) can in turn cause blue-black skin, eye, or tooth discoloration that can nullify its benefits, resulting in suboptimal patient adherence to cancer therapy. Although this adverse effect is well known in dermatology literature as a risk when using minocycline to treat acne, rosacea, or blistering disorders, it is less well documented in oncology literature. We present this case to highlight the need for greater consideration of unique patient characteristics in selecting an oral antibiotic as a treatment modality for EGFR inhibitor skin toxicities.

Differential diagnosis of melasma and hyperpigmentation

“…A number of different medications have been associated with skin pigmentation, including neurological medications (chlorpromazine, amitriptyline), cytotoxic agents (bleomycin, anthracycline), analgesics, anticoagulants, antimicrobials (chloroquine, minocycline), antiretrovirals, metals, and antiarrhythmics (amiodarone). 21 Drug-induced hyperpigmentation can occur at any age and often presents as a slate-gray coloration affecting the face and other areas of the body. shins, scar sites) assisting clinicians in their diagnosis (Table 2).…”

“…Some medications cause the synthesis of new pigment (lipofuscin) or the accumulation of iron and lysis of red blood cells (minocycline). 21,22 Diagnosing drug-induced hyperpigmentation can prove difficult and clinicians should be vigilant in examining a patient's complete medical history to determine the specific culprit and rule out other conditions that may be leading to skin findings.…”

“…A number of different medications have been associated with skin pigmentation, including neurological medications (chlorpromazine, amitriptyline), cytotoxic agents (bleomycin, anthracycline), analgesics, anticoagulants, antimicrobials (chloroquine, minocycline), antiretrovirals, metals, and antiarrhythmics (amiodarone) 21 …”

“…Some medications trigger an accumulation of melanin (antimalarials) which is often found to be worse in sun‐exposed areas, while other medications accumulate within dermal macrophages and cause pigmentation itself. Some medications cause the synthesis of new pigment (lipofuscin) or the accumulation of iron and lysis of red blood cells (minocycline) 21,22 . Diagnosing drug‐induced hyperpigmentation can prove difficult and clinicians should be vigilant in examining a patient's complete medical history to determine the specific culprit and rule out other conditions that may be leading to skin findings.…”