By definition, the term postinflammatory hyperpigmentation (PIH) refers to discoloration that develops after inflammation associated with a cutaneous event resolves, but there appears to be insufficient appreciation for the fact that PIH and inflammation can coexist, according to the authors of a Viewpoint recently published in JAMA Dermatology.

The authors, led by Jerry K. L. Tan, MD, adjunct professor of dermatology at the University of Western Ontario in London, Ontario, Canada, believe this has important implications when using the term PIH.

By diagnosing a post-inflammatory process, “clinicians may then focus solely on pigment-targeted therapy” rather than the inflammation that is continuing to drive PIH, Tan and his colleagues explained. This results in a missed opportunity to continue anti-inflammatory therapy until this cause of hyperpigmentation is eliminated, they said.

Ongoing Inflammation Should Be Ruled Out

“Clinicians should reserve the term PIH for situations in which inflammatory activity has reasonably resolved and avoid using it when ongoing inflammation is present or strongly suspected,” they added.

The problem caused by a premature diagnosis of PIH is particularly common in patients with inflammatory dermatologic disorders that are chronic or frequently recur, such as acne, and in patients with darker skin tones in which erythema is easy to miss.

“The concern in darker skin is that ongoing inflammation is more difficult to recognize because increased epidermal melanin reduces the visibility of erythema,” Tan told Medscape Medical News. “This makes persistent inflammation more likely to be underrecognized and the lesions more readily labeled incorrectly.”

Of several studies he and his coauthors cited, a prospective evaluation of patients with Fitzpatrick skin types II-VI and acne-associated hyperpigmentation showed persistent erythema with objective colorimetric analyses that confirmed the coexistence of hyperpigmentation and inflammation.

The message from this study is that “visible hyperpigmentation may mask persistent erythema and should not be assumed to indicate resolved inflammation,” Tan and his colleagues wrote.

They also referred to a histologic study performed with skin biopsies obtained 28 days after induction of inflammation. The lesions were classified as PIH, but persistent lymphocytic infiltration was readily observed.

There is evidence that treating inflammation does improve coexisting hyperpigmentation, supporting the principle that all patients with PIH deserve careful evaluation for ongoing inflammation. For example, a phase 3b study of the interleukin-13 inhibitor lebrikizumab in adults and adolescents with atopic dermatitis reduced hyperpigmentation even away from sites of active inflammation, according to Tan.

In another published report, a patient with a relatively dark skin tone and recalcitrant lichen planus pigmentosus experienced a reduction in hyperpigmentation when treated with a topical JAK inhibitor (ruxolitinib, 1.5% cream), which the authors suggested is “consistent with a role for persistent immune signaling in at least some pigmentary change.”

No Special Workup for Inflammation Advised

While Tan and his coauthors are not calling for the use of biopsies, colorimetry, or other specialized testing for detection of ongoing inflammation in a patient with clinical signs of PIH, they counseled clinicians to be alert for signals, including subtle signals of itch, induration, or scale, particularly in patients with darker skin tones.

This is not just because inflammation is harder to detect in patients with darker skin tones but because patients with darker skin appear to be more prone to persistent inflammation after hyperpigmentation develops. “Evidence from imaging studies does show that risk of hyperpigmentation coexisting with ongoing inflammation is greater in patients with darker skin tones,” Tan said in the interview.

Specifying that PIH is a useful term and should not be abandoned, Tan emphasized that there is a risk of applying it as an initial clinical impression. Instead, the diagnosis should be made after considering and evaluating patients for an ongoing inflammatory process. By approaching PIH with a diagnostic bias, it threatens to limit further investigation.

“More precise terminology — recognizing that some hyperpigmentation is inflammation that is not purely postinflammation — is needed,” he said.

Refraining from the term PIH until inflammation has been ruled out may support treatment of the underlying inflammation “to improve outcomes for people with hyperpigmentation in whom persistent inflammation might otherwise be underrecognized,” according to Tan.

Asked to comment, Marissa Joseph, MD, associate professor in the Division of Dermatology, University of Toronto, and medical director of the Ricky Kanee Schacter Dermatology Center at Women’s College Hospital, both in Toronto, Ontario, Canada, called the premise of this Viewpoint “a clinical pearl.”

Senior author of a review of PIH published earlier this year, Joseph called the importance of screening for inflammation in patients with a clinical presentation consistent with PIH “a useful reminder” rather than “an entirely new concept.”

The premise is sound, and the label PIH creates premature diagnostic closure, Joseph explained in an interview, but she suggested that this clinical pearl would be even more compelling with evidence of benefit.

“Further study would help determine whether this more deliberate assessment for persistent inflammation ultimately improves patient outcome,” she said.

Tan reported having financial relationships with Avene, Bausch, Galderma, L'Oréal, and Sanofi, and nonfinancial support from Skinopathy. The other authors also disclosed relationships with several companies; the full list can be found in the publication. Joseph reported having financial relationships with Bausch and L'Oréal.

Ted Bosworth, a career medical writer based in New York City, has been covering advances in clinical medicine, including dermatology, for several decades.