Updated Review of Genetic Reticulate Pigmentary Disorders

J. Zhang; M. Li; Z. Yao


The British Journal of Dermatology. 2017;177(4):945-959. 

In This Article

Reticulate Acropigmentation of Kitamura

RAK was first reported in Japanese patients, but has now been found in every ethnic group worldwide.[50] RAK clinically manifests as reticulate, slightly depressed, sharply demarcated brown macules without hypopigmentation that mainly affect the dorsa of the hands and feet (Figure 7). In some cases, the pigmentation may also spread to the limbs, neck and forehead. The onset age for RAK ranges from 5 to 12 years.[20] Histopathologically, the hyperpigmented macules show pigmentation in the tips of the rete ridges with thinning of the epidermis, elongation and thinning of the rete ridges and slight hyperkeratosis without parakeratosis.[20] Under electron microscopy, an increased number of melanosomes can be observed in the cytoplasm of keratinocytes in the area of the hyperpigmented macules.

Figure 7.

Clinical features of reticulate acropigmentation of Kitamura in a patient: reticular pigmentation predominantly on the dorsa of the hands and feet.

In 2013, mutations in the ADAM metallopeptidase domain 10 (ADAM10) gene were found to cause RAK (Table S4; see Supporting Information).[50] The encoded protein, a disintegrin and metalloproteinase domain-containing protein (ADAM)10, is another key protein in the Notch signalling pathway and is required for activation of NOTCH1 through a proteolytic mechanism initiated by ligand binding, which may modulate the distribution patterns or transport processes of melanosomes in keratinocytes.[51]

Differential Diagnosis

Age of onset, the distribution of lesions, lack of hypopigmented macules, as well as the particular histological and genetic findings help to distinguish RAK from similar reticulate pigmentary disorders, such as DDD.[20]

Clinical Management

Treatment options for the hyperpigmented lesions are similar to those for DDD. One patient was reported to be treated with 20% azelaic acid ointment, and improvement of the pigmentation following treatment was observed within several weeks,[52] suggesting a potential treatment option.