What is the most likely diagnosis and appropriate management for a 42‑year‑old patient with lifelong genetically determined mottled hyperpigmentation that began at age 7 and is now most prominent on the face?

Dyschromatosis Universalis Hereditaria: Diagnosis and Management

Most Likely Diagnosis

The clinical presentation of genetically determined mottled hyperpigmentation beginning at age 7 and progressing to involve the face in a 42-year-old patient is most consistent with Dyschromatosis Universalis Hereditaria (DUH). 1

Clinical Features Supporting This Diagnosis

• DUH characteristically presents with multiple irregular hyperpigmented macules interspersed with hypopigmented macules in a mottled pattern over the trunk and extremities 1
• Facial involvement occurs in approximately 50% of individuals with DUH 1
• Skin lesions typically appear in infancy or early childhood (consistent with onset at age 7) and cease to progress beyond adolescence 1
• The condition follows an autosomal dominant inheritance pattern in most cases (DUH types 1 and 3), with DUH type 2 showing autosomal recessive inheritance 1

Genetic Basis

• The most common gene involved in DUH is ABCB6, while other implicated genes include SASH1, PER3, and KITLG (in DUH type 2) 1
• Targeted gene sequencing can confirm the diagnosis when clinical presentation is uncertain 1

Differential Diagnosis to Exclude

The following conditions should be considered and ruled out:

• Dyschromatosis Symmetrica Hereditaria (DSH/Reticulate acropigmentation of Dohi) - differs in distribution pattern 1
• Unilateral dermatomal pigmentary dermatosis - presents with unilateral rather than generalized involvement 1
• Vitiligo with hyperpigmentation - would show complete depigmentation rather than mottled pattern 2
• Postinflammatory pigmentary changes - would have history of preceding inflammation 2

Diagnostic Workup

A systematic diagnostic approach should include:

• Dermoscopy to characterize the pigmentary pattern and distribution 1
• Histopathology showing variation in melanin content between hyperpigmented and hypopigmented areas 1
• Electron microscopy can reveal differences in melanosome size and number, though this is rarely necessary 1
• Targeted gene sequencing for ABCB6, SASH1, PER3, and KITLG mutations to confirm diagnosis and determine subtype 1

Screening for Associated Conditions

DUH has been reported in association with various cutaneous and systemic diseases, requiring vigilance for:

• Hepatocellular carcinoma 1
• Solitary keratoacanthoma 1
• Other cutaneous and systemic manifestations 1

Regular dermatologic surveillance is recommended, though specific screening intervals are not established in the literature 1

Management Approach

Realistic Expectations

No treatment modality has proven consistently effective for DUH, and patients should be counseled accordingly. 1

Treatment Options That Have Been Attempted

• Narrowband UVB (NB-UVB) phototherapy has been tried but shows limited efficacy 1
• Laser treatments have been attempted without promising results 1
• Topical depigmenting agents like hydroquinone are not recommended for this condition, as they are designed for localized hyperpigmentation rather than the mixed mottled pattern of DUH 3

Photoprotection

Sun exposure should be minimized on affected areas, as UV radiation can exacerbate pigmentary changes:

• Application of broad-spectrum sunscreen (SPF 15 or greater) to prevent further pigmentary alterations 3
• Use of protective clothing and sun avoidance during peak hours 2

Cosmetic Camouflage

Camouflage cosmetics represent the most practical management approach for patients concerned about appearance:

• Professional instruction in camouflage techniques can significantly improve quality of life 2
• This approach is particularly important for facial involvement, which affects 50% of patients 1

Psychological Support

Given the visible nature of facial involvement and the chronic, progressive course during childhood:

• Psychological counseling should be offered to address coping mechanisms and potential psychosocial impact 2, 4
• This is particularly important as pigmentary disorders can cause low self-esteem, social anxiety, and stigmatization 2

Important Clinical Caveats

• The condition typically stabilizes after adolescence, so patients should be reassured that progression will likely cease 1
• Avoid aggressive treatments with significant side-effect profiles, as the condition is benign and primarily cosmetic 1
• Document the distribution and characteristics with serial photographs to monitor for any atypical changes that might suggest associated conditions 4
• Family screening may be appropriate given the autosomal dominant inheritance pattern in most cases 1