Classification of polygenic inflammatory diseases distributed along the lines of Blaschko.

gator for over 30 years in the field of the nosology of Blaschko-linear diseases. He recently introduced the concept of ‘superimposed segmental manifestation’ to describe severe segmental involvement in polygenic diseases [5] , since the designation ‘type 2 segmental manifestation’ should be restricted to diseases with monogenic mendelian inheritance. Indeed, it is (yet) not possible in polygenic diseases to distinguish between type 1 segmental manifestations, which reflect heterozygosity for a post-zygotic new mutation occurring in an otherwise healthy individual, and type 2 segmental manifestations. We are currently working on a comprehensive classification of polygenic inflammatory diseases distributed along the lines of Blaschko, and we reviewed the cases that were managed in our department during the past 10 years [6] . We think that Happle’s proposal should be expanded and that 4 conceptually different situations need to be individualized in order to classify polygenic inflammatory diseases along the lines of Blaschko. In type 1 , disease involvement occurs exclusively along the lines of Blaschko. Obviously, this can never be ascertained, since the patient can develop involvement outside the lines of Blaschko in the future. However, in the case of inflammatory diseases exclusively localized along the lines of Blaschko, 2 situations need to be individualized. In this issue of Dermatology , Boente et al. [1] report an 8-year-old boy with juvenile dermatomyositis who developed Blaschko-linear bands of calcification on the left lower limb. We follow up a patient with similar clinical findings. At the age of 12 years he developed Blaschkolinear lines of calcified nodules on the lower limb ( fig. 1 ) for which he consulted. On examination he was found to have typical signs of dermatomyositis ( fig. 2 ). Boente et al. discuss the possibility that loss of heterozygosity could explain this unusual segmental manifestation of dermatomyositis, by analogy to what has been described under the designation of type 2 segmental manifestations in monogenic diseases [2] . In the latter situation, this mechanism has been proven, as for example in Hailey-Hailey disease [3] . The rationale of this assumption is as follows. If the effect of a pathologic gene that would predispose to a specific disease, for instance dermatomyositis, is not balanced by the effect of the normal gene inherited from the other parent, its effect will be increased. Therefore, in cells where only the pathologic gene is present, either homozygous or hemizygous, the disease expression will be enhanced. However, direct evidence of this mechanism in polygenic inflammatory diseases is missing. Mosaicism has been proved only once in a patient with adult-onset blaschkitis [4] . One of Boente’s co-authors, Rudolf Happle, has been the leading investiPublished online: May 14, 2009