A study in the August Journal of Drugs in Dermatology addressed the burden of melasma – the populations most prone to melasma and the comorbidities associated with it. According to the study’s authors, a deeper understanding of the associations of race, ethnicity and comorbidities can help dermatologists determine which patients are at risk of developing melasma and as well as potential new pathways for treatment.
I interviewed author Ajay Nair Sharma, MD, MBA, a dermatology resident at the University of California, Irvine, Department of Dermatology.
What led you to want to investigate the burden of melasma?
Melasma is one of the most frustrating dermatologic conditions to treat for both patients and providers, with a classic predominance in those of skin of color. Despite its prevalence, there is a dire need for advanced understanding of its etiopathology to develop efficacious and targeted therapies. By using large scale data, we sought to identify significant factors for developing melasma to allow for better stratification of and intervention in those at risk.
You utilized a large global health research network database to look at the associations of race, ethnicity and comorbidities with melasma prevalence. What did you discover?
Utilizing a global database allowed for the analysis of over 40,000 patients with melasma, leading to high statistical significance of our findings. Interestingly, the most strongly associated comorbidities included rosacea (odds ratio=5.1), atopic dermatitis (OR=3.3), lupus (OR=2.5), history of skin cancer (OR=2.5), history of internal malignancy (OR=2.1) and hormonal contraception use (OR=2.1) With respect to race and ethnicity, there exists significant associations for melasma in Asian or Other/Unknown races (OR=2.0 and OR=1.7), as well as Hispanic ethnicity (OR=1.3).
Were any of the results surprising?
Our latest global update on the association of skin of color and comorbidities of melasma identifies a preference in melanized phenotypes (Fitzpatrick skin type III-V), but less so in extreme skin types (I, II, VI). Additionally, associations with a history of skin cancer and internal malignancy have not been previously reported, and it was fascinating to see these strong odds ratios in a predominantly female and middle-aged population.
How are these results helpful in understanding and treating melasma?
An enhanced understanding of the risk factors associated with melasma allows for speculation of therapeutic pathways.
The melasma cohort had a higher association with atopic dermatitis, possibly related to overactive mast cells present in both conditions. Biologic targeting of mast cell degranulation or its downstream effects may thus be an area with future therapeutic potential.
With higher rates of cutaneous malignancy, melasma patients may share pathophysiology in the form of higher sun exposure, hormonal stimuli, altered oxidative status and/or impaired skin barrier. Associations between a history of internal malignancy and melasma are more difficult to explain, possibly related to higher inflammatory states or hormonal milieu changes, whether disease-specific or iatrogenic.
What should dermatology clinicians do differently in light of this study?
Increased associations with rosacea, atopic dermatitis and history of cancer may emphasize the importance of treating concurrent inflammatory environments and the consideration of more frequent malignancy surveillance.
What are other important takeaways from this study?
Systemic hormonal contraception (i.e. oral birth control pills) and anticonvulsants also revealed significant positive odds ratios, emphasizing need for early recognition and timely modification of therapy for appropriate patients with hyperpigmentation. In the melasma cohort, topiramate (2418, 26%), lamotrigine (907, 10%) and levetiracetam (424, 5%) were the most implicated anticonvulsants, with the latter two established as two of the safest during pregnancy. A consistent association between autoimmune hypothyroidism, hyper-estrogen states and melasma has been previously reported and is supported in our study.
Do you plan to conduct any additional research into the burden of melasma and, if so, what factors will you investigate?
Our titular conclusion remains: The global burden of melasma is vast. With new associations with cutaneous and internal malignancy, further study into a casual or correlative relationship is warranted. Furthermore, with a prominent vascular component in many presentations of melasma, as well as a robust overlap with rosacea, interventions targeting blood flow (i.e. pulsed dye laser) may serve as a useful adjunct.
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