What causes hypopigmentation?

Causes of Hypopigmentation

Hypopigmentation results from reduced melanin production or melanocyte loss, with causes ranging from genetic disorders to acquired conditions including autoimmune disease, post-inflammatory changes, infections, and rare immunodeficiency syndromes.

Genetic and Immunodeficiency Causes

Rare genetic syndromes with hypopigmentation should be suspected when accompanied by specific systemic features:

Chédiak-Higashi Syndrome (CHS)

• Oculocutaneous albinism with recurrent pyogenic infections, bleeding tendency, and giant lysosomal granules in all granulated cells including melanocytes 1
• Mutations in LYST gene cause abnormal lysosomal trafficking affecting melanosomes, platelet-dense bodies, and cytolytic granules 1
• Peripheral blood smear showing giant azurophilic granules is pathognomonic and should be the first diagnostic test 1
• Most patients develop hemophagocytic lymphohistiocytosis (HLH) "accelerated phase" with fever, hepatosplenomegaly, pancytopenia, and neurological deterioration that is fatal without aggressive treatment 1

Griscelli Syndrome (GS)

• Three subtypes exist, with GS2 presenting as oculocutaneous hypopigmentation, silvery grey hair, recurrent pyogenic infections, and risk of fatal HLH 1
• GS1: hypopigmentation with neurological abnormalities (seizures, ataxia), minimal infections, MYO5A mutations 1
• GS2: hypopigmentation with infections and HLH risk, RAB27A mutations 1
• GS3: isolated hypopigmentation without infections or neurological signs, MLPH mutations 1
• Hair shows large melanin clumps in shaft; skin shows melanosome retention in melanocytes 1
• Pigmentary changes present from birth, with infections and hepatosplenomegaly beginning in infancy 1

Hermansky-Pudlak Syndrome (HPS)

• Oculocutaneous albinism with severe thrombocytopenia/thrombasthenia; HPS2 specifically presents with neutropenia and recurrent infections 1
• Nine distinct gene defects (HPS1-9) cause abnormal cellular granules similar to CHS and GS2 1
• HPS2 is important cause of idiopathic pulmonary fibrosis, though less frequent than other HPS subtypes 1

Autoimmune Causes

Vitiligo

• Progressive loss of functioning epidermal melanocytes causing depigmented patches, strongly associated with autoimmune thyroid disease in 34% of adults 2, 3
• Non-segmental vitiligo: symmetrical patches that increase over time, average onset age 20 years 2
• Segmental vitiligo: unilateral distribution following dermatomes or Blaschko's lines, suggesting neural basis 2, 3
• Common sites include fingers, wrists, axillae, groins, and body orifices (mouth, eyes, genitalia) 2, 3
• Thyroid function and thyroid autoantibodies should be checked in all vitiligo patients 2
• Wood's light examination delineates pigment loss, particularly useful in lighter skin types 2, 3

Scleroderma-Associated Depigmentation

• Screen for Raynaud phenomenon, digital ulcers, interstitial lung disease, and pulmonary arterial hypertension when encountering unexplained depigmentation with suspected connective tissue disease 4
• Immunosuppressive treatment of underlying scleroderma may benefit depigmentation, though no established evidence-based treatments exist specifically for the depigmentation 4

Lichen Sclerosus

• Presents as hypopigmented patches with inflammation, particularly in genital area 1
• Can be differentiated from vitiligo by associated inflammation, texture changes, and anatomic distribution 1

Post-Inflammatory Hypopigmentation

Inflammation or trauma to skin can result in temporary or permanent melanocyte dysfunction:

• Sequelae of inflammatory dermatoses (eczema, psoriasis), infections, or therapeutic interventions including photodynamic therapy 1, 5, 6
• More prominent in darker skin types with greater cosmetic and psychosocial impact 6
• Most cases resolve spontaneously over time, though duration varies 5, 6
• Individual "chromatic tendency" based on melanocyte response patterns may determine whether hypopigmentation or hyperpigmentation develops after inflammation 5
• PDT-induced hypopigmentation is dose-dependent, occurs 48-72 hours post-treatment, and is generally mild 1

Infectious Causes

Pityriasis Alba

• Localized hypopigmented disorder of childhood, more detected in darker complexions but occurs in all skin types 7
• Associated with atopy, xerosis, and mineral deficiencies 7
• Poor cutaneous hydration appears central to pathogenesis, resulting in inappropriate melanosis 7
• Sun exposure exacerbates contrast between normal and lesional skin 7

Pityriasis Versicolor Alba

• Must be differentiated from vitiligo, nevus depigmentosus, and nevus anemicus 7

Common Diagnostic Pitfalls

• Failing to screen for thyroid disease in vitiligo patients misses treatable autoimmune condition affecting one-third of adults 2
• Not recognizing systemic features (infections, bleeding, neurological signs) that distinguish genetic immunodeficiency syndromes from isolated pigmentary disorders 1
• Overlooking psychological impact of visible depigmentation on quality of life regardless of underlying cause 2, 6
• Missing underlying connective tissue disease when depigmentation occurs with other systemic symptoms 4