Lithium is a foundational medication used primarily as a mood stabilizer for individuals with bipolar disorder and major depressive disorder. While highly effective for managing severe mood changes, it is associated with a range of side effects, including dermatological reactions. Acneiform eruption, an acne-like rash, is recognized as one of the most common skin-related adverse effects of this medication. The prevalence of acne in patients taking lithium can be as high as 45% in some studies, highlighting the need to understand its underlying cause.
Lithium’s Impact on Inflammatory Pathways in the Skin
The development of acne while taking lithium involves the skin’s inflammatory and cellular regulation systems. The drug’s mechanism of action in the brain is theorized to be connected to its effects on cellular signaling pathways throughout the body, including the skin. Lithium is known to influence the production of inflammatory chemicals called cytokines, which are small proteins that regulate immune responses.
Lithium is proposed to increase the production of these inflammatory chemicals, triggering inflammation in the skin. This inflammation often involves the migration of white blood cells known as neutrophils into the skin. Their increased activity in the skin’s follicle suggests a simulated inflammatory state, leading to the formation of acne-like lesions.
Lithium also appears to interfere with the normal life cycle of skin cells within the hair follicle. The drug’s effect on cellular messengers can lead to a lack of proper differentiation and increased proliferation of keratinocytes, the cells that line the hair follicle. This excessive cell growth contributes to follicular plugging, which is the initial step in acne formation.
Another pathway implicated is the mammalian target of rapamycin (mTOR) signaling pathway, which controls cell growth and metabolism. Activation of the mTOR pathway by lithium is hypothesized to increase both cell proliferation and the production of sebum, or skin oil. Excessive sebum production combined with follicular plugging and inflammation creates the ideal environment for the development of acne lesions.
Clinical Presentation of the Acne
Lithium-induced acne often presents differently from the common acne vulgaris seen in adolescence. The lesions are typically described as an acneiform eruption, characterized by a uniform appearance of persistent, red, inflammatory bumps and pus-filled pimples (monomorphic papules and pustules). Unlike typical acne, this drug-induced form frequently lacks the presence of blackheads and whiteheads, or comedones.
The distribution of the lesions is also a distinguishing factor, as the acne often appears on the limbs and trunk, including the chest and back, rather than being concentrated solely on the face. In more severe cases, the inflammation can progress to deeper, painful nodules or cysts, occasionally leading to conditions like acne conglobata. Folliculitis, the inflammation of the hair follicles, can also occur, presenting as tender red pustules, often on the forearms and legs.
The onset of the skin condition can vary significantly among patients, but it usually appears several weeks to a few months after starting lithium treatment or after a dosage increase. While the severity does not always correlate with the patient’s lithium blood levels, a past or family history of acne may predispose an individual to a more pronounced eruption. The condition may also represent an exacerbation of pre-existing acne.
Dermatological Management Strategies
Managing lithium-induced acne requires balancing treatment of the skin condition with maintaining necessary mental health treatment. Patients should never discontinue or adjust their lithium dosage without first consulting with their prescribing physician due to the risk of destabilizing their mood disorder. In many cases, the benefits of the medication outweigh the discomfort of the skin condition, and treatment focuses on managing the dermatological symptoms while continuing the drug.
Topical treatments are the first line of defense and include standard acne medications: retinoids, benzoyl peroxide, and topical antibiotics. Topical retinoids, such as tretinoin, work to unclog pores and promote skin peeling, effective against the follicular plugging component. Combining these topical agents often provides a multi-pronged approach to address inflammation and cell turnover.
For severe or widespread cases, systemic treatments, such as oral antibiotics, may be necessary. However, physicians must be mindful of potential drug interactions; for example, some antibiotics, like tetracyclines, can affect lithium excretion, potentially leading to toxic lithium levels. Oral isotretinoin, a highly effective systemic retinoid, is reserved for the most severe, unresponsive cases and requires careful monitoring when used alongside lithium.
In consultation with the psychiatric team, a dose adjustment may be considered if the acne is severe and unresponsive to conventional dermatological treatment. Monitoring serum lithium levels is necessary, and sometimes a slight reduction in dosage, if medically appropriate, can help alleviate the skin side effects. In rare instances where the acne is severe and resistant to treatment, the prescribing doctor may consider switching the patient to an alternative mood stabilizer.