Facial dyspigmentation is a frustrating disorder to patients, particularly in Asian countries (12). Topical agents inhibiting synthesis or transfer of melanin, as well as enhancing exfoliation of preexisting melanin pigment have been used as the first-line treatment (34567). Lasers and light-based devices working on pigment have been used with variable success (8). However, certain type of acquired facial hyperpigmentation shows different clinical features and unexpected responses to conventional treatment (9). Multiple laser treatments combined with topical whitening agent may not be effective, with clinical aggravation even after the multiple treatments (3).

Recently, we have experienced patients with distinctive bilateral or symmetric hyperpigmentation often extending to neck, which failed to respond conventional treatment for hyperpigmentation. To provide clarification, clinical characteristics, histopathological features, and other diagnostic examination as well as responses to treatments were evaluated in this study.

All 31 patients presented with distinctive bilateral or symmetric bizarre hyperpigmentation of face and/or neck. Most of the patients were elderly with female preponderance, along with chronic or refractory course of disease (mean duration; over 2 years). Pigmentation generally manifested as brown to slate-grey color with ill-defined margin. The lateral face (forehead and both cheeks) was uniquely involved and hyperpigmentation affected both sun-exposed and non-exposed area in neck. Perioral accentuation of pigmentation was another noticeable finding.

All enrolled patients were initially diagnosed as melasma at other clinics and most underwent multiple laser treatments before visiting our clinic. Melasma is usually pronounced in mid face, as a malar prominence or peri-ocular in middle aged women (6). Also it is associated with pregnancy, ultraviolet exposure, oral contraceptives and endocrine dysfunctions (11), which were not found in our patients. Histopathologically, melasma shows increased epidermal melanin, rather than dermal melanin (12). Distinctive liquefactive degeneration of basal laser is not a common finding in the lesion of melasma. These clinical and histopathological findings of our patients suggest a disease entity other than melasma.

Lichen planus pigmentosus (LPP) or Ashy dermatosis (AD: erythema dyschromicum perstans) should be taken into account for this clinical condition. LPP and AD commonly presented as ill-defined oval, greyish brown pigmentation on the face and neck or trunk and limbs without an inflammatory phase. Clinical manifestation of our patients was different from LPP and AD. No patients showed any truncal involvement. Lichenoid lympho-histiocytic infiltration or colloidal body in the epidermis was not prominent in the histopathological examination, which is the characteristic feature of two similar pigmentary disorders of LPP and AD (13).

The vacuolar change of basal layer without spongiosis accompanying dermal melanin deposition, implies the possibility of similar underlying pathomechanism as seen in pigmented contact dermatitis (PCD), also known as Riehl’s melanosis (14). PCD is a rare variant of non-eczematous contact dermatitis, which is believed to be caused by repetitive contacts with very small amounts of allergens, such as washing powder, fragrance or cosmetics (1516). The small amount of allergen induces spongiosis in epidermis, rather than the classical symptoms of contact dermatitis that include erythema, edema and vesicle formation. On the contrary, as subclinical damage persists, vacuolar change of basal layer results in pigmentary incontinence. Clinically, melanin pigment in upper dermis is so slowly absorbed that the hyperpigmentation appears to persist or worsen over time if consistent contact of possible allergens happens (17). Riehl’s melanosis, first described by Riehl as “war melanosis” in 1917, similarly affects the face, and is related with nutritional factors and sensitizing chemicals in cosmetics (181920). Riehl’s melanosis is considered synonymous with PCD, with the common allergen being fragrances and chemicals in cosmetics (19). Clinical and histological manifestation of our patients looked similar to that of PCD. Presently, 19 patients were presumed to involve personnel causative allergens including hair dyes (63.2%, 12/19 cases) and cosmetics (36.8%, 7/19 cases); however, no patient showed positive in the “as is” test with suspected product. Some patients (17 out of 25 patients) demonstrated positive result in T.R.U.E test, but their clinical relevance is doubtful due to lack of prolonged use of personnel cosmetics or fragrances based on their personal history. None of patients recalled any preceding erythema or itching which can be a possible sign of contact dermatitis. We did not perform photopatch test on these patients. For patients who presented with skin lesion especially on sun exposed area, photopatch test can be helpful for the exact diagnosis (21). However, patients in this analysis did not show definite photo-related skin lesion. Photos from Fig. 1 demonstrated prominent pigmentary disturbance on perioral and lateral face rather than on the central area. The central neck area especially right under the chin is usually spared in photo-related disease unlike our patients who showed whole neck involvement of skin lesion. Laboratory tests, such as IgE or eosinophil cationic protein (ECP), which reflect allergic tendency, were not increased except one patient (22). The histological findings of our patients, which included basal layer disruption without spongiosis, suggest underlying subclinical inflammatory process as seen in PCD, which are not preceded by an obvious inflammatory injury. Therefore, the most plausible diagnosis would be PCD in our patients, although there was no definite relation of causative allergens with skin lesion found through all examination.

Considering that most of our patients had tried repetitive laser treatments, it is possible that basal layer disruption is caused by unknown inflammatory causes as well as subclinical wounding incurred during laser treatments. The clinical course in which dyspigmentation worsens in many patients after the application of multiple laser treatments supports the possibility that repetitive laser treatments might play a role in disease progression. This hypothesis needs more study.

The bizarre pigmentation in our patients was primarily due to dermal melanin deposition, mainly in dermal melanophages. Melanophages are primarily the result of cutaneous inflammatory process that affects the dermo-epidermal interface leading to deposition of pigment within dermis (23). Thus, the control of cutaneous inflammatory process should be prioritized in this condition, especially before laser treatment, which can cause superimposed subclinical inflammation, leading to secondary hyperpigmentation or pigmentary worsening. The triggering factors of inflammation are usually deducted by knowledge of a patient’s history and location of inflammation. But, for some diseases like PCD, which feature barely distinguishable inflammation, thorough history-taking and patch test should be done to identify any possible causative allergen. Histologic evaluation of pigmented lesion (skin biopsy) provides a diagnostic clue and valuable information of depth of pigment location and distribution as well as dermal nature which requires for optimal treatments. Punch biopsy of pigmentary lesion (2 to 3 mm) is sufficient with minimal risk of scarring. Concurrent evaluation of peri-lesional normal skin can provide better precise information in interpreting pathologic change of dyspigmentation (12). However, facial hyperpigmentation of women, especially middle aged Asians, are frequently considered as melasma, whether it is or not. Sometimes, active laser therapy is tried based on this tentative diagnosis without suspicion of other disorders. However, this approach is unsatisfactory as there are many pigmentary disorders that clinically mimic melasma and the distinction between them invariably requires astute histopathological evaluation and subsequent clinical correlation (3).

When it comes to the optimal treatment modalities in these patients, laser therapy for hyperpigmentation should not be the first choice if there is a severe basal layer disruption and solar elastosis. Presence of liquefactive degeneration of basal layer and dense inflammatory cell infiltration in dermis suggests accumulative inflammatory damage (16), therefore topical agents of anti-inflammatory activity, not depigmenting or whitening agents should be used first. According to this well-defined step-by-step approach, among 12 patients who suffered with refractory, long-lasting dyspigmentation was considerably improved (Figs. 4 and 5). This approach is summarized in Fig. 6. Two of 7 patients who used only topical anti-inflammatory agents and moisturizers achieved excellent clinical improvement.

The histopathologic findings and the prolonged course of the hyperpigmentation in our cases were both suggestive of a preceding causative subclinical inflammatory process. The underlying cause remains uncertain and multiple factors may have produced this clinical feature. When approaching to this long-lasting or refractory facial dyspigmentation, clinicians should consider a step-by step approach. Step 1 involves checking the underlying allergic tendency with thorough history taking and/or blood lab. Step 2 involves determining the degree of inflammation and resiliency of dermis whether it could be properly restored after laser treatments. Step 3 is the application of a topical agent capable of reducing inflammation for at least months. Step 4 should consider possible adequate methods for removal of remnant pigments as the last step of treatment.

We present 31 patients with peculiar clinical feature and long-lasting course hyperpigmentation on the face and neck. The use of a systematic step-by-step approach with appropriate therapeutic modality can provide clinical benefit.