What causes acneiform eruptions in patients with polycystic ovary syndrome (PCOS)?

Causes of Acneiform Eruptions

Acneiform eruptions are primarily caused by medications (particularly EGFR inhibitors, corticosteroids, androgens, and immunosuppressants), hormonal excess (especially androgens in conditions like PCOS), or drug-induced inflammatory responses affecting sebaceous glands.

Medication-Induced Acneiform Eruptions

EGFR Inhibitors and Targeted Cancer Therapies

• EGFR inhibitors cause acneiform rash in 75-90% of patients (all grades) and 10-20% experience grade 3-4 severity, typically developing within the first days to weeks of therapy 1, 2.
• The mechanism involves dense periadnexal leucohistiocytic inflammatory infiltrate with clustering of macrophages, Langerhans cells, T cells, mast cells and neutrophils 2.
• EGFR inhibitor-induced secretion of chemokines and cytokines by epidermal keratinocytes drives the inflammatory response 2.
• Because EGFRs are highly expressed in sebaceous epithelium, eruptions concentrate in seborrheic areas such as the scalp, face, neck, chest, and upper back, with periorbital region, palms, and soles typically spared 1.
• The acneiform eruption is dose-dependent and begins within 1 week of treatment 1.

MEK Inhibitors

• MEK inhibitors cause papulopustular eruption in 74-85% (all grades) and 5-10% (grade 3-4) of patients 2.

Other Medications

• Corticosteroids, lithium, phenytoin, isoniazid, vitamins B2, B6, and B12, halogens, testosterone, progesterone, and immunosuppressants all cause acneiform eruptions 3, 4, 5.
• Tyrosine kinase inhibitors (TKIs) for chronic myeloid leukemia cause rash in 20-43% of patients, with bosutinib causing rash in 43% (6% grade 3-4) in second-line use 2.

Hormonal Causes (PCOS Context)

Androgen Excess

• Androgens, such as testosterone and dehydroepiandrosterone sulfate, have central roles in the pathogenesis of acne by triggering sebum production and sebaceous growth and differentiation 1, 3.
• Polycystic ovarian syndrome is a common cause of hyperandrogenism, characterized by ovulatory dysfunction or polycystic ovaries on ultrasonography 1.
• Excess production of hormones, specifically androgens, GH, IGF-1, insulin, CRH, and glucocorticoids, is associated with increased rates of acne development 3.

Clinical Indicators for Hormonal Testing

• Patients presenting with acne and clinical signs or symptoms of hyperandrogenism, such as hirsutism, oligomenorrhea or androgenic alopecia, infertility, clitoromegaly, and truncal obesity warrant further endocrine testing 1.
• Tests for serum total and/or free testosterone, dehydroepiandrosterone sulfate, luteinizing hormone, follicle-stimulating hormone may be considered 1.
• Routine endocrinologic testing is not indicated for most patients with acne 1.

Distinguishing Features of Acneiform Eruptions

Key Differentiating Characteristics

• Unlike true acne, acneiform eruptions have sudden onset, widespread involvement, occur in unusual locations, occur beyond typical acne age, consist of monomorphous lesions, and clear after the offending drug has been discontinued 4.
• Comedones are typically absent in drug-induced acneiform eruptions 5.
• Follicular inflammatory papulopustules distributed on the face and trunk are typical of acneiform drug eruptions 5.

Bacterial Superinfection

• Bacterial colonization or superinfection develops in up to 38% of cases, requiring vigilant monitoring 2.
• When infection is suspected (failure to respond to oral antibiotics covering gram-positive organisms, presence of painful skin lesions, pustules in arms, legs and trunk, yellow crusts, discharge), bacterial culture must be obtained 1.

Critical Clinical Pitfalls

• Do not confuse drug-induced rash with life-threatening conditions like Stevens-Johnson syndrome or toxic epidermal necrolysis, which require immediate hospitalization and discontinuation of all suspected agents 2.
• The association between acne severity and androgen levels remains unclear, with some studies showing positive associations while others showed no associations 1.
• Paradoxically, occurrence and severity of rash with EGFR inhibitors correlate positively with therapy response and improved survival 2.