Acquired Dermal Macular Hyperpigmentation

Acquired dermal macular hyperpigmentation (ADMH) encompasses a group of chronic acquired pigmentary dermatoses characterized by the presence of dermal pigmentation.¹ Clinically, ADMH may be asymptomatic or present with mild pruritus, predominantly manifesting as non-scaly macules or patches that range from gray and slate-blue to dark brown (Figure 1). ADMH conditions typically involve the face, neck, and other photo-exposed or friction-prone areas but can also extend to the trunk and proximal extremities.¹ Beyond the classic presentations, rare morphological variants have been identified, including periorbital and follicular variants, which present as localised periocular pigmentation or pinpoint follicular macules, respectively.^2,3

Given that the pigmentation is located within the dermis, the condition is often refractory to standard topical lightening agents. Consequently, ADMH has a substantial impact on quality of life, with a recent systematic review demonstrating a psychosocial burden comparable to that of vitiligo and significantly greater than that of melasma.⁴ Factors such as younger age, female gender, and longer disease duration have been associated with poorer quality-of-life outcomes and higher rates of psychiatric comorbidity.⁴

Figure 1. Gray to slate-blue patches with a surrounding inflammatory border. The peripheral color change may appear more visibly erythematous in lighter skin (A), while in darker skin (B) it may present as a more subtle violaceous, dusky, or hyperpigmented rim.

Consensus Regarding Nomenclature

Historically, the spectrum of dermatoses that fell under the umbrella of ADMH was described as distinct conditions. These included lichen planus pigmentosus (Figure 2), erythema dyschromicum perstans (historically termed "ashy dermatosis", a descriptor that may carry unintended negative social connotations)⁵ (Figure 3), Riehl melanosis, and idiopathic eruptive macular pigmentation (Figure 4).¹ However, there was considerable overlap among these conditions, which often led to diagnostic uncertainty and confusion. To address this, a 2023 global Delphi consensus reached more than 80% expert agreement to consolidate these entities under the unifying term ADMH, which more accurately reflects their shared clinical and histological characteristics.⁵ It has also been proposed to subclassify ADMH into two broad categories, ADMH with contact sensitization and ADMH without contact sensitization.¹ This is relevant as identifying an extrinsic trigger informs management strategies.

Figure 2. Slate-gray to blue-gray patches involving the lateral cheeks, temples, and preauricular areas in a patient with lichen planus pigmentosus (LPP).

Figure 3. Early active erythema dyschromicum perstans (EDP) on the arm, showing faint erythematous (inflammatory) borders surrounding brown patches.

Figure 4: Round-to-oval macules and patches on the extremities, some with an ash-coloured peripheral hue, in a teenage boy with idiopathic eruptive macular pigmentation (IEMP).

Pathogenesis

While the exact pathogenesis of ADMH remains to be fully elucidated, it is widely regarded as a multifactorial process. It likely arises from a complex interplay of genetic susceptibility, systemic autoimmunity, and environmental triggers, culminating in a lichenoid tissue reaction.⁶

Immunological and Genetic Factors

Recent research has established a strong link between ADMH and autoimmunity. Patients may present with concurrent conditions such as autoimmune thyroiditis, frontal fibrosing alopecia (FFA), and connective tissue diseases. A recent case-control study exploring Human Leukocyte Antigen (HLA) allele frequencies identified associations with several alleles, most notably HLA-A*03:01, HLA-B*07:02, HLA-C*07:02, and HLA-DRB1*10:0.⁷ These findings suggest a genetic predisposition toward enhanced CD8+ T-cell–mediated cytotoxicity targeting basal keratinocytes, representing a key step in ADMH pathogenesis.⁸

Environmental Triggers

A subset of ADMH, particularly the Riehl melanosis phenotype, is driven by a Type IV delayed hypersensitivity reaction.9 Commonly implicated triggers include paraphenylenediamine found in hair dyes, as well as henna, fragrances, and cosmetic preservatives.^1,10 Exposure to these allergens, often exacerbated by ultraviolet or visible light, triggers a cytolytic interface dermatitis.¹⁰ This process leads to the leakage of melanin into the dermis, where it is phagocytosed by melanophages, resulting in persistent dermal pigment incontinence.6

Molecular Biomarkers

Emerging evidence has highlighted the role of dermal fibroblasts and neuroendocrine factors in regulating melanogenesis in ADMH. Studies measuring cutaneous biomarkers have shown that Dickkopf 1 (DKK1), a fibroblast-secreted inhibitor of the Wnt signalling pathway, is significantly downregulated in affected skin. Neuregulin 1 (NRG1), an epidermal growth factor that stimulates melanocyte proliferation, has been found to be markedly upregulated in ADMH. The expression levels of these proteins correlate strongly with disease severity, providing a molecular basis for increased pigmentary activity and offering potential novel therapeutic targets.¹¹

Clinical Assessment

A detailed history and examination are essential for navigating the complexities of ADMH, identifying potential triggers, and excluding alternative causes of hyperpigmentation.

Associated Conditions

In addition to other autoimmune conditions, ADMH has a known association with FFA[NE2.1].¹² In many patients, particularly postmenopausal women, macular hyperpigmentation on the face and neck can serve as a herald sign preceding the cicatricial hair loss seen in FFA.¹² The association with other autoimmune conditions is supported by recent HLA genetic profiling, which confirms a shared underlying autoimmune susceptibility.¹

Dermoscopic Findings

Dermoscopy is a useful non-invasive tool that can be used to assist in the diagnosis of ADMH and other hyperpigmentary conditions, and to monitor disease activity. Dermoscopy typically reveals brown, black, or blue-gray dots and/or globules that characteristically spare the eccrine and follicular openings. While specific pigment arrangements correlate with the histopathological severity of pigment incontinence, these patterns are diagnostic aids and not required for diagnosis.¹³

Biopsy

A skin biopsy is not always mandatory to establish a diagnosis of ADMH when clinical and dermoscopic features are classic. However, when performed, histopathology can be confirmatory. It typically demonstrates basal cell vacuolization, a variably dense lymphohistiocytic interface infiltrate, and prominent dermal melanophages indicative of pigment incontinence.1

Further Investigations

As the histological hallmark of ADMH is interface dermatitis, there is significant pathological overlap with connective tissue diseases. Therefore, it is recommended to exclude systemic disorders that may present with similar macular hyperpigmentation through appropriate autoimmune serological testing.

Differential Diagnosis

Differentiating ADMH from other hyperpigmentary disorders requires careful clinical evaluation:^1,14

• Post-inflammatory hyperpigmentation: typically preceded by a history of overt inflammation and lacks the characteristic lichenoid interface changes on biopsy.
• Drug-induced pigmentation: must be excluded by a thorough medication history (eg, minocycline, antimalarials, or nonsteroidal anti-inflammatory agents).
• Melasma: characteristically favors the malar and mandibular regions and is exacerbated by hormonal fluctuations, whereas ADMH  frequently involves the preauricular area and neck.
• Macular amyloidosis: typically involves the upper back and presents with a classic rippled pattern of pigmentation.
• Other differential diagnoses to consider include nevus of Ota, poikiloderma of Civatte, and acanthosis nigricans.

Current Treatment Approach

Management of ADMH remains challenging due to the absence of standardised, high-level evidence-based protocols. A sequential, two-pronged approach is generally required, involving initial stabilization of active disease followed by treatment of residual dermal pigmentation.1

Trigger Avoidance

Before initiating therapy, potential triggers must be identified and eliminated. Patch testing is recommended to rule out pigmented contact dermatitis.1 Strict photoprotection against both ultraviolet and visible light is a cornerstone of management.1 Disease severity should be objectively measured using the Dermal Pigmentation Area and Severity Index (DPASI), a validated scoring system that grades severity based on involved surface area and dermoscopic pigment patterns.¹⁵

Stabilizing Active Disease

ADMH is considered active if new lesions are appearing or existing macules demonstrate progression. To suppress the underlying interface dermatitis, systemic immunosuppressive or immunomodulatory therapies may be required. Options include oral mini-pulse corticosteroids, mycophenolate mofetil, low-dose oral isotretinoin, colchicine, and hydroxychloroquine (plaquneil). Adjunctive topical therapies, including corticosteroids and calcineurin inhibitors, may also be utilized.¹

Clearing Residual Pigmentation

Once the disease is completely stabilized, a process that can take several months, physical modalities can be employed to target dermal melanophages. While laser and chemical peels have been reported as moderately helpful in some cases, both carry paradoxical risk of worsening pigmentation and post-inflammatory hyperpigmentation. Picosecond lasers may be of greater benefit but are yet to be explored in robust clinical trials.¹

Future Directions

Future research in ADMH should address key gaps that currently limit evidence-based care. The existing literature consists largely of small observational studies and case series, highlighting a critical need for well-designed trials to inform treatment choices. Broad adoption of validated outcome measures, such as the DPASI, is essential to allow for meaningful comparisons across studies. In addition, larger multi-center studies with longer follow-up periods are needed to better define treatment durability, relapse rates, and optimal duration of therapy, particularly given the chronic and relapsing nature of the condition.

Further investigation is needed to elucidate the pathogenesis underlying ADMH, particularly the interplay between genetic susceptibility, immune dysregulation, and environmental triggers. The paucity of data regarding treatment efficacy across diverse skin types, particularly in darker phototypes disproportionately affected by ADMH, also needs to be addressed,¹⁶ along with the significant but underexplored psychosocial burden through a patient-centred approach.