Segmental Pigmentation Disorder

M. Hogeling; I.J. Frieden

Disclosures

The British Journal of Dermatology. 2010;162(6):1337-1341. 

In This Article

Discussion

Our case series, together with the series described more than 25 years ago by Metzker et al.,[1] emphasizes the clinical characteristics of SegPD. SegPD may or may not be evident at the time of birth, but most cases have an early age of onset (median 0·25 months in our study) suggesting a developmental origin which is evident at birth or shortly thereafter. Some authors propose that the reason SegPD may be noted later during infancy is that newborn skin tends to be hypopigmented and sun protected.[7,8]

The patterns of distribution, with sharp demarcation at the midline, also suggest that the condition is most probably due to a somatic mutation reflecting disparate pigmentation properties. The pattern of SegPD most resembles the 'checkerboard' pattern described by Happle as a form of presumed somatic mosaicism seen in several birthmarks, most notably port-wine stains and speckled lentiginous naevus[6] (Fig. 1). Typically it is not dermatomal, nor does it follow the lines of Blaschko. Solitary lesions are probably due to the spectrum of a mosaic condition. As reported previously, the most common location is the torso (Fig. 2), followed by the extremities, face and neck.[1,7–9] Along the midline most patients have a ventral delineation, but some have dorsal delineation. Occasionally SegPD may cross the midline, and we suggest that the lesion may cross the midline a few centimetres before excluding SegPD. Metzker et al.[1] observed that the lateral border of SegPD is often less distinct and we also observed this in our patients. They also reported that the pigmentary differences may fade over time in some patients; although we do not have long-term follow-up on our patients, the presence of two adults in our series suggests that SegPD may persist into adulthood at least in some cases.

Figure 1.

A 4-month-old girl with a 'checkerboard' pattern of segmental pigmentation disorder (SegPD) characterized by alternating squares of hyperpigmentation with midline demarcation, demonstrating that SegPD sometimes involves both sides of the body.

Figure 2.

A 6-month-old boy with segmental pigmentation disorder. In this case well-demarcated, unilateral block-like hyperpigmentation is seen crossing the midline ventrally and extending to his back.

We found a low risk of extracutaneous abnormalities (three of 39) and in no case could we be confident that the abnormalities noted (ASD, strabismus with retinal hypopigmentation and bronchogenic cyst) were truly associated, although both ASD and strabismus have been noted as extracutaneous features in mosaic pigmentary disorders.[10] There are rare reports of naevus depigmentosus (ND) being associated with central nervous system findings, but in a large majority of cases, there are no systemic or neurological abnormalities.[8–11] Kim et al.[8] reported one patient with localized ND and seizures out of 60 patients studied. Nehal et al.[12] found one out of nine patients with segmental ND had systemic findings. Our series combined with that of Metzker et al. suggests that the risk of associated abnormalities in SegPD is quite low.

The histopathological correlates of SegPD depend upon whether hyper- or hypopigmentation is present. We did not biopsy any of our patients, but the case of hyperpigmented SegPD biopsied by Metzker et al.[1] showed increased melanin present in the basal layer, suggesting increased melanin production, similar to a café-au-lait macule. Somewhat more is known about the pathology of segmental hypopigmentation. Melanin content has been found to be slightly decreased by silver stain and electron microscopy, but the number of melanocytes is reportedly normal or decreased.[7–9] Kim et al.[8] biopsied 60 patients with ND, 32 of whom probably had SegPD, and found that melanocytes were decreased with MART-1 stain, but not with S-100. It is hypothesized that ND is caused by a functional alteration of melanocytes, such as decreased transfer of melanosomes to keratinocytes.[7,9,13]

The differential diagnosis of segmental hyperpigmentation includes large and giant café-au-lait macules, McCune–Albright syndrome, speckled lentiginous naevus, naevoid hyperpigmentation and segmental neurofibromatosis. SegPD may be called giant café-au-lait macules, but café-au-lait macules have different features. Most café-au-lait macules do not have sharp midline demarcation and tend to be more oval or round without fading at their lateral border, but they can have virtually identical histopathology.[1,2,14]

Hyperpigmented macules are also a feature of McCune–Albright syndrome, but the pattern in McCune–Albright syndrome most often follows the so-called broad lines of Blaschko and the pigmentation may be darker in colour than that typical of SegPD. The presence of other findings of this condition, including precocious puberty and polyostotic fibrous dysplasia, helps distinguish it from SegPD, but these findings may lag behind the pigmentary changes.[15–17]

Speckled lentiginous naevi may take several years for the characteristic spotted lesions within a hyperpigmented patch to become evident. As in SegPD, speckled lentiginous naevi may have sharp demarcation at the midline, and early speckled lentiginous naevi can be difficult to exclude in young infants.[18] In our study, several patients were excluded because of the suspicion they had or were evolving toward speckled lentiginous naevi. In older children speckled lentiginous naevi can be distinguished from SegPD by the presence of multiple naevi within the lighter brown patch. Dermoscopy can be a helpful tool to reveal evidence of a true pigment network which would not be a feature of SegPD. Naevoid hyperpigmentation involves hyperpigmentation along the lines of Blaschko, and the narrower, sometimes whorled pattern, differs from the block-like pattern of SegPD. There may be rare patients with overlapping features. Segmental neurofibromatosis can manifest as a large segmental café-au-lait macule, but the presence of multiple smaller café-au-lait macules within the area (analogous to axillary or inguinal 'freckling') either with or without neurofibromas is helpful in distinguishing this condition from SegPD. A dermatomal, rather than a segmental pattern, is more often evident.[19] In evaluating very young infants with segmental hyperpigmentation, parents should be advised to return if more changes such as new café-au-lait macules develop to exclude the possibility of evolving neurofibromatosis.

The differential diagnosis of segmental hypopigmentation (Fig. 3) includes tuberous sclerosus, segmental vitiligo and naevus anaemicus. Tuberous sclerosis does not usually have a segmental pattern, and typically consists of multiple hypopigmented oval, ash-leaf or polygonal macules in children with associated angiofibromas, seizures or developmental delay. Cases of segmental tuberous sclerosis have rarely been described but the cutaneous finding reported is typically segmental angiofibromas and to our knowledge cases presenting as segmental hypopigmentation have not been reported.[20]

Figure 3.

A 4-year-old boy with segmental pigmentation disorder since birth, consisting of a hypopigmented, localized, block-like patch involving his right chest and axilla.

SegPD can usually be distinguished from segmental vitiligo by clinical differences, e.g. the affected skin is hypopigmented rather than truly depigmented, the borders of vitiligo are more sharply demarcated, and the age of onset (typically vitiligo occurs in somewhat older children or adults). Naevus anaemicus is caused by differences in local circulation rather than a disorder of hypopigmentation. Although not segmental in distribution, it may occasionally be confused with SegPD; however, it disappears with diascopy and is accentuated by stroking adjacent skin.[21] Naevoid hypopigmentation along the lines of Blaschko is usually relatively easy to distinguish clinically from SegPD, but some authors clearly lump SegPD within the general diagnosis of 'naevoid' pigmentary disorders. As discussed above, we have chosen to separate these conditions because of their distinct clinical patterns.[10,22]

SegPD is usually a sporadic condition but occasionally there is a positive family history, present in two of the patients in the study by Metzker et al.[1] (who were siblings) and two unrelated patients in our series, giving a rate of 6%. The pattern of SegPD suggests postzygotic somatic mosaicism, but the evidence for this is circumstantial and has not been proven. Those cases with a positive family history suggest paradominant inheritance as a possible mechanism.[6]

This condition is not a rare one. As mentioned, we saw at least 18 patients in the year preceding this retrospective analysis and possibly others were missed due to lack of clinical photographs as this was our method of patient ascertainment. The disparate terminology used to describe this condition has made it more difficult to study and characterize. Some have argued that the term 'segmental pigmentation disorder' is either linguistically imprecise or that this condition along with macular pigmentation following the lines of Blaschko should be subsumed under the umbrella term 'naevoid pigmentary abnormalities'. We disagree as the patterns of SegPD are nearly always clinically distinct from those following the lines of Blaschko and may ultimately prove to have differing mechanisms or genes involved. The term 'segmental' is well established in medicine (i.e. segmental vitiligo, segmental neurofibromatosis, etc.), nearly always referring to checkerboard or dermatomal patterning. 'Segmental pigmentation disorder' is a better term than 'naevus achromians' or similar terms used previously and we propose that until specific genes or mechanisms are identified which can explain these pigmentary changes, the term 'segmental pigmentation disorder' first proposed by Metzker et al. be used as the best name to describe the segmental hypo- and hyperpigmentation described herein.

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