Primary immunodeficiency associated with hypopigmentation: A differential diagnosis approach

Allergol Immunopathol (Madr). 2021 Mar 1;49(2):178-190. doi: 10.15586/aei.v49i2.61. eCollection 2021.


Primary immunodeficiency diseases (PIDs) are a group of more than 400 disorders representing aberrant functioning or development of immune system. Hypopigmentation syndromes also characterize a distinguished cluster of diseases. However, hypopigmentation may also signify a feature of genetic diseases associated with immunodeficiency, such as Chediak-Higashi syndrome, Griscelli syndrome type 2, Hermansky-Pudlak syndrome type 2 and type 10, Vici syndrome, and P14/LAMTOR2 deficiency, all of which are linked with dysfunction in vesicular/endosomal trafficking. Regarding the highly overlapping features, these disorders need a comprehensive examination for prompt diagnosis and effective management. As an aid to clinician, distinguishing the pathophysiology, clinical phenotype, and diagnosis as well as treatment options of the six mentioned PID disorders associated with hypopigmentation are described and discussed in this review.

Keywords: Chediak–Higashi syndrome; Griscelli syndrome type 2; Hermansky–Pudlak syndrome; P14 deficiency; Vici syndrome; differential diagnosis; hypopigmentation syndromes; inborn errors of immunity; primary immunodeficiency.

Publication types

  • Review

MeSH terms

  • Diagnosis, Differential
  • Genetic Testing*
  • Humans
  • Hypopigmentation / diagnosis*
  • Hypopigmentation / genetics
  • Hypopigmentation / immunology
  • Hypopigmentation / therapy
  • Primary Immunodeficiency Diseases / diagnosis*
  • Primary Immunodeficiency Diseases / genetics
  • Primary Immunodeficiency Diseases / immunology
  • Primary Immunodeficiency Diseases / therapy
  • Skin Pigmentation / genetics
  • Skin Pigmentation / immunology