aDouglas C. Wu, MD, PhD; bRichard E. Fitzpatrick, MD; bMitchel P. Goldman, MD aGoldman, Butterwick, Groff, Fabi and Wu Cosmetic Laser Dermatology, San Diego, California; bGoldman, Butterwick, Fitzpatrick, Groff and Fabi: Cosmetic Laser Dermatology, San Diego, California
Disclosure: The authors report no relevant conflicts of interest.
Abstract
Diagnostic uncertainty when a patient presents with melasma-like findings can lead to suboptimal treatment and inaccurate prognostic expectations. In this study, the authors present a unique clinical feature of melasma that they term the “Fitzpatrick macule” and test its utility in establishing diagnostic certainty. The “Fitzpatrick macule” is a confetti-like macule of regularly pigmented skin located within a larger patch of melasma hyperpigmentation. To test its diagnostic utility, the authors compared clinical photography of known cases of melasma with common mimickers, such as poikiloderma of Civatte and solar lentiginosis, and determined the positivity rate of the Fitzpatrick macule in each scenario. Their results show that 89.1 percent of clinical photographs of melasma were positive for the presence of Fitzpatrick macules compared to 1.1 percent that were negative. In contrast, 37.5 and 56.3 percent of clinical photographs of poikiloderma of Civatte were positive and negative for Fitzpatrick macules, respectively. Solar lentiginosis showed a 5.6 percent positivity and a 77.8 percent negativity for Fitzpatrick macules. The sensitivity and specificity of Fitzpatrick macules for melasma was 99 and 83 percent, respectively. In summary, the authors report a highly sensitive and specific clinical feature of melasma. In cases of diagnostic uncertainty, the presence of Fitzpatrick macules may aid in establishing a diagnosis of melasma. (J Clin Aesthet Dermatol. 2016;9(2):48–57.)
Melasma is a common pigmentary disorder often seen in patients with skin phototypes III to IV.[1] Worldwide prevalence is variable. In a study by Werlinger et al,[2] the prevalence of melasma in post-menopausal Latino women living in Texas was reported at 8.8 percent. On the other hand, Southeast Asian populations have had a reported prevalence of melasma as high as 40 percent.[1] The etiology and pathogenesis of melasma remains poorly understood, but is thought to be a combination of various factors, such as ultraviolet (UV) exposure, genetics, and hormonal influences. Clinically, it is typically described as a symmetric, well-demarcated, irregularly shaped, macular hyperpigmentation most often affecting the face with characteristic distribution in various well-recognized patterns (centrofacial, malar, mandibular, mixed). Histologically, the abnormal pigmentation may be found in the epidermis, the dermis, or both. Treatment options include topical bleaching regimens, chemical peels, and light and laser modalities.[3] However, complete clearance of hyperpigmentation can sometimes be difficult to achieve, and recalcitrant cases of melasma are not uncommon, leading to significant patient distress and physician frustration.[4]
Compounding the difficulty in treating melasma is the diagnostic uncertainty that occasionally accompanies the patient presentation. Currently, there are no universally accepted clinical or histopathological diagnostic criteria for melasma. Additionally, the pathogenesis is unknown and often the exact same treatment can result in different outcomes for what is supposedly identical disease. A recent Cochrane review concluded that the largest published reports on melasma in fact had poorly defined patient selection criteria,[5] indicating that even the leading experts were not in agreement as to which patients should be included in a “melasma” study. Taken together, these facts suggest that although diagnostic uncertainty in regards to melasma is rarely publicized, it nonetheless exists.
A common mimicker of melasma is simple accumulated actinic dyschromia. This is the well-known phenomenon of irregular dyspigmentation of the skin that occurs as part of the chronic photoaging process.[6],[7] It typically responds extremely well to various types of laser treatments, whereas those same treatments may be problematic in melasma. Other entities could potentially add to the confusion, such as solar lentigines, poikiloderma of Civatte, postinflammatory hyperpigmentation, drug-induced hyperpigmentation, and less commonly café au lait macules, nevus of Ota, nevus of Ito, and actinic lichen planus. Because each of the above entities present different therapeutic challenges to the treating physician, with varying degrees of response rates and treatment modalities, it is crucial to arrive at an accurate clinical diagnosis of melasma. To that end, the authors test the diagnostic utility of a highly unique feature of melasma—confetti-like areas of sparing within the hyperpigmented patches giving the impression of hypopigmented macules. The authors term these areas “Fitzpatrick macules” and analyze their utility in helping to establish a diagnosis of melasma.
MATERIALS AND METHODS
A pubmed search of the English language literature was conducted. Studies on melasma of the face and neck were reviewed between January 1, 2010, and January 1, 2013. All studies with clinical photography were included for evaluation. No age, gender, skin phototype, or race restrictions were applied. Exclusion criteria included those articles that could not be accessed electronically, those that did not include clinical photography, and those that simultaneously looked at pigmentary disorders other than melasma. The exact same search methodology was then applied to both “poikiloderma of Civatte” (literature reviewed from 1990–2013) and “solar lentigines” (literature reviewed from 1980–2013). A search was attempted for “actinic bronzing,” but due to the paucity of literature on this entity, no analysis could be performed. Clinical photographs were extracted from the included manuscripts and then randomized for evaluation in a blinded fashion. Patients were sorted into the following three groups: 1) positive for Fitzpatrick macules, 2) indeterminate for Fitzpatrick macules, and 3) negative for Fitzpatrick macules. The results were tabulated and analyzed in graphical format. Vascularity of Fitzpatrick macules was assessed on live patients with an established diagnosis of melasma in the authors’ clinic with VISIA Complexion Analysis (Canfield Scientific, Inc., Fairfield, New Jersey) as previously described.[8] Statistical analysis was performed via the Kruskal-Wallis and Mann-Whitney tests.
By non-selectively sampling all published images of melasma (before treatment) in the literature, the authors reduce diagnostic bias and inaccuracy as compared to selecting melasma patients based on a single physician’s or group of physicians’ patient populations. In the absence of perfectly defined diagnostic criteria for melasma, the next gold standard becomes what the collective medical community defines as melasma in the cumulative academic literature. This prevents the authors own selection bias from confounding the results. Regarding ethics approval, institutional review board/human subjects committee approval was waived due to there being no identifiable live patient involvement in this study.
RESULTS
A title keyword search of the English language literature for “melasma” on pubmed revealed 120 articles published between January 1, 2010, and January 1, 2013. Of these, 55 (46%) studies included photographic evidence of known cases of melasma. Similarly, “poikiloderma of Civatte” revealed 19 search responses of which 10 (53%) had clinical photography. Of 51 published articles on “solar lentigines”, 13 (25%) included clinical photography (Table 1 ).
Fitzpatrick macules can be defined as the macular, confetti-like normally pigmented skin measuring approximately 2 to 4mm in diameter within the hyperpigmented patches of melasma that are usually associated with hypervascularity. This distinct clinical feature can be seen in Figure 1. The authors then analyzed the vascular nature underlying the Fitzpatrick macule. As has been previously reported, the hyperpigmentation of melasma is often associated with an underlying hypervascularity.8 Evaluation of the Fitzpatrick macule, however, revealed that it is relatively spared this hypervascularity phenomenon (Figure 2).
Next, the authors determined the utility of the Fitzpatrick macule at aiding in the diagnosis of melasma. Of the 92 clinical photographs of melasma patients included in the articles reviewed within this study, 82 (89.1%) were positive for Fitzpatrick macules. An additional nine (9.8%) were indeterminate for Fitzpatrick macules. This indeterminate state was usually due to the quality of the photograph being insufficient to definitively assess the presence or absence of Fitzpatrick macules. Only one (1.1%) clinical photograph of melasma was rated as not having evidence of Fitzpatrick macules. Analysis of 16 clinical photographs of poikiloderma of Civatte revealed that six (37.5%) displayed Fitzpatrick macules, nine (56.3%) were negative, and one (6.2%) was indeterminate. For solar lentiginosis, a total of 18 clinical photographs were analyzed. One (5.6%) was positive for Fitzpatrick macules, 14 (77.8%) were negative, and three (16.7%) were indeterminate. These data are represented graphically in Figure 2, Figure 3, and Figure 4. Based on these data, the sensitivity and specificity of Fitzpatrick macules in the diagnosis of melasma is 99 and 83 percent, respectively.
DISCUSSION
The results in this study show that Fitzpatrick macules are found in virtually all patients with facial melasma, making them highly sensitive findings for the clinical diagnosis of this condition. Furthermore, the fairly high specificity of these data suggests that the presence of Fitzpatrick macules can be a useful distinguisher between other common mimickers of melasma. Actinic dyschromia could not be formally analyzed by the methodology in this report due to its scarcity in the medical literature. However, the authors’ experience, as shown in Figure 1, suggests that the Fitzpatrick macule can be a useful distinguisher in these subtle cases. This is important from a patient and physician perspective because actinic dyschromia often has a far more predictable and favorable response to laser correction, with a reduced risk for postinflammatory or rebound hyperpigmentation as compared to melasma. Hence, because diagnostic uncertainty can sometimes exist in the patient who presents with melasma-like findings, and because many melasma “mimickers” have different treatment protocols and prognostic expectations, the Fitzpatrick macule would be a useful tool in allowing physicians to deliver appropriate patient care and counseling.
Hypopigmentation in association with melasma has previously been noted. For example, confetti-like hypopigmentation of the face was reported by Chan et al[9] following low fluence laser toning of melasma with the Q-switched 1064nm Nd:YAG.[9] This finding was thought to be secondary to treatment. Many clinicians may also note islands of hypopigmentation within patches of melasma and mistakenly characterize them as previous “scar” from excoriation or inflammatory acne (even though the patient typically denies both vehemently). Additionally, sun exposure can reveal the previously subtle hyperpigmentation of undiagnosed melasma by conversely accentuating the relative sparing of the Fitzpatrick macule. The Melasma Area Severity Index (MASI) proposed in 1994 by Kimbrough-Green et al[10] was based on global assessments of broad anatomic units of the face (forehead, right malar, left malar, and chin).[10] Homogeneity was loosely defined on a scale of “patchinesss.” A recent validation of the MASI, however, determined that the homogeneity score was the least reliable of all MASI metrics and could be completely eliminated without any effect on the validity of the scoring.[11] The unique and characteristic pigmentary sparing as defined by the Fitzpatrick macule is an important refinement of the melasma homogeneity concept due to its high diagnostic sensitivity and specificity as well as its implications on pathogenesis of disease.
The exact etiology and pathogenesis of melasma remains unclear. One hypothesis is that a significant portion of melasma patients also have an underlying hypervascularity that contributes to melanocyte dysfunction. This hypothesis is supported by the fact that melasma appears to respond well to treatment modalities that target both pigment and vessels, such as intense pulsed light (IPL).[8] Furthermore, one study showed an association between pigmented areas of melasma and underlying hypervascularity.[8] The data in this report show that the Fitzpatrick macule is spared this hypervascularity, which may account for its relatively normal pigmentation. Indeed, when Fitzpatrick macules are taken into account, the patches of melasma often assume a marked reticulated or retiform pattern—a morphological descriptor most classically associated with lesions that are due to underlying abnormalities in vascular networks. Further scientific and clinical evaluation of the possible role of vascular dysfunction in the pathogenesis of melasma is warranted.
The clinical significance and diagnostic utility of the Fitzpatrick macule has not previously been reported in the melasma literature. By defining this entity, the authors provide a useful tool by which physicians can establish a diagnosis of melasma
ACKNOWLEDGMENTS
The authors are indebted to the diligent efforts of the clinical, research, and technical staff at Goldman, Butterwick, Fitzpatrick, Groff, & Fabi: Cosmetic Laser Dermatology.
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