10.5826/dpc.1203a130
Introduction: Incontinentia pigmenti (IP) is a rare X-linked geno-dermatosis characterized by numerous findings. Skin biopsy and histopathological analysis are considered as minor criteria for the diagnosis of IP. We assume that dermoscopy can assist the earlier diagnosis of IP.
Objectives: To gain experience in earlier diagnosis of IP by observing dermoscopic findings of cutaneous changes.
Methods: We revised confirmed cases of IP and examined them using dermoscopy, comparing histopathological and dermoscopic results. 
Results: Stage I presented solitary and grouped vesicles in linear arrangement on erythematous skin. Early stage II presented star-shaped verrucous lesions on erythematous or pigmented skin. In well-developed lesions, dotted vessels surround keratotic part, some with thrombosed capillaries, resembling a viral wart. Stage III presented linear brown dots on the pigmented areas. Dermoscopic image was uniform in all the examined pigmented Blaschko linear changes. Stage IV presented numerous dotted vessels on the hypopigmented skin. Terminal hair was scarce or absent in all four stages. The surrounding normal skin had perifollicular depigmentations in stages III and IV.
Conclusions: Dermoscopy of all four stages is very specific compared to the dermoscopy of inflammatory dermatoses and pigmentations. Stage III has very close clinical, histological and dermoscopic mimickers and needs to be carefully examined with obligatory genetic testing. Dermoscopy of the stage IV closely corresponds to histopathological findings and may be crucial as a quick tool in revealing potential IP gene carriers. Dermoscopy should be used in addition to clinical examination since the two methods are complementary.
text/xml
2160-9381
2011
en
Dusan Trpinac
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
dermoscopy
Dermatoscopy in the Diagnostics of Incontinentia Pigmenti Skin Lesions
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Original Article
2022-07-28
2021-09-08
2022-07-28
2022-09-14
e2022130
Dermatol Pract Concept
Introduction: Incontinentia pigmenti (IP) is a rare X-linked geno-dermatosis characterized by numerous findings. Skin biopsy and histopathological analysis are considered as minor criteria for the diagnosis of IP. We assume that dermoscopy can assist the earlier diagnosis of IP.
Objectives: To gain experience in earlier diagnosis of IP by observing dermoscopic findings of cutaneous changes.
Methods: We revised confirmed cases of IP and examined them using dermoscopy, comparing histopathological and dermoscopic results. 
Results: Stage I presented solitary and grouped vesicles in linear arrangement on erythematous skin. Early stage II presented star-shaped verrucous lesions on erythematous or pigmented skin. In well-developed lesions, dotted vessels surround keratotic part, some with thrombosed capillaries, resembling a viral wart. Stage III presented linear brown dots on the pigmented areas. Dermoscopic image was uniform in all the examined pigmented Blaschko linear changes. Stage IV presented numerous dotted vessels on the hypopigmented skin. Terminal hair was scarce or absent in all four stages. The surrounding normal skin had perifollicular depigmentations in stages III and IV.
Conclusions: Dermoscopy of all four stages is very specific compared to the dermoscopy of inflammatory dermatoses and pigmentations. Stage III has very close clinical, histological and dermoscopic mimickers and needs to be carefully examined with obligatory genetic testing. Dermoscopy of the stage IV closely corresponds to histopathological findings and may be crucial as a quick tool in revealing potential IP gene carriers. Dermoscopy should be used in addition to clinical examination since the two methods are complementary.
Dusan Trpinac
2022/07/28
10.5826/dpc.1203a130
e2022130
Institute of Histopathology, Faculty of Medicine, University of Belgrade, Serbia
2160-9381
dermoscopy
en
e2022130
Al-Refu K. Dermoscopy is a new diagnostic tool in diagnosis of common hypopigmented macular disease: A descriptive study. Dermatol Reports. 2018;11(1):7916. DOI: 10.4081/dr.2018.7916. PMID: 31119026.
Dermatoscopy in the Diagnostics of Incontinentia Pigmenti Skin Lesions
https://dpcj.org/index.php/dpc/article/download/2011/1684
                    Dermatology Practical & Conceptual


     Dermoscopy in the Diagnostics of Incontinentia
                Pigmenti Skin Lesions
          Snezana Minic1,2, Danijela Dobrosavljevic1,2, Jovan Lalosevic1,2, Dusan Trpinac2,3


1 Clinic of Dermatovenerology, University Clinical Center of Serbia, Belgrade, Serbia
2 Faculty of Medicine, University of Belgrade, Belgrade, Serbia
3 Institute of Histology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia



Key words: Incontinentia pigmenti, skin stages, skin histopathology, Blaschko lines, dermoscopy
Citation: Minic S, Dobrosavljevic D, Lalosevic J, Trpinac D. Dermoscopy in the Diagnostics of Incontinentia Pigmenti Skin Lesions.
Dermatol Pract Concept. 2022;12(3):e2022130. DOI: https://doi.org/10.5826/dpc.1203a130
Accepted: December 17, 2021; Published: July 2022
Copyright: ©2022 Minic et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-
NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use,
distribution, and reproduction in any medium, provided the original authors and source are credited.
Funding: None.
Competing interests: None.
Authorship: All authors have contributed significantly to this publication.
Corresponding author: Danijela Dobrosavljevic, PhD, Pasterova 2, Phone numbers: +38164 1649422, Fax: +381 11 2642648 E-mail
address: danijela_dobrosavljevic@yahoo.co.uk




  ABSTRACT              Introduction: Incontinentia pigmenti (IP) is a rare X-linked geno-dermatosis characterized by nu-
                        merous findings. Skin biopsy and histopathological analysis are considered as minor criteria for the
                        diagnosis of IP. We assume that dermoscopy can assist the earlier diagnosis of IP.
                        Objectives: To gain experience in earlier diagnosis of IP by observing dermoscopic findings of cuta-
                        neous changes.
                        Methods: We revised confirmed cases of IP and examined them using dermoscopy, comparing histo-
                        pathological and dermoscopic results.
                        Results: Stage I presented solitary and grouped vesicles in linear arrangement on erythematous skin.
                        Early stage II presented star-shaped verrucous lesions on erythematous or pigmented skin. In well-
                        developed lesions, dotted vessels surround keratotic part, some with thrombosed capillaries, resembling
                        a viral wart. Stage III presented linear brown dots on the pigmented areas. Dermoscopic image was
                        uniform in all the examined pigmented Blaschko linear changes. Stage IV presented numerous dotted
                        vessels on the hypopigmented skin. Terminal hair was scarce or absent in all four stages. The surround-
                        ing normal skin had perifollicular depigmentations in stages III and IV.
                        Conclusions: Dermoscopy of all four stages is very specific compared to the dermoscopy of inflam-
                        matory dermatoses and pigmentations. Stage III has very close clinical, histological and dermoscopic
                        mimickers and needs to be carefully examined with obligatory genetic testing. Dermoscopy of the
                        stage IV closely corresponds to histopathological findings and may be crucial as a quick tool in reveal-
                        ing potential IP gene carriers. Dermoscopy should be used in addition to clinical examination since the
                        two methods are complementary.




Original Article | Dermatol Pract Concept. 2022;12(3):e2022130                                                                       1
Introduction                                                     and grouped vesicles in a linear arrangement with yellowish
                                                                 content and serocrusts on an erythematous skin. Skin hair
Incontinentia pigmenti (IP; Bloch-Sulzberger syndrome) is a      was significantly reduced on the affected area. In stage II,
rare X-linked genetic disorder with an estimated prevalence      early verrucoid lesions are star-shaped, yellowish or whit-
of 1.2/100.000 [1,2]. It appears almost exclusively in females   ish on an erythematous and a slightly pigmented skin. In
and is usually lethal in males [3]. It is caused by a mutation   well-developed lesions, dotted vessels surround a central ker-
of the IKBKG gene localized on the X chromosome locus            atotic part, or can be distributed on the lesion, with throm-
Xq28, which is the only gene known to be associated with         bosed capillaries, strikingly resembling a viral wart.
IP [2]. The most prominent clinical manifestations of IP are
considered to be skin changes, which constitute major IP         Case 2
diagnostic criteria [4,5]. Skin changes in IP occur along the
                                                                 The proband was one and a half months old at the initial
lines of Blaschko throughout four stages: vesiculobullous
                                                                 visit, phototype IV, presented with hyperpigmented maculas
(I), verrucous (II), hyperpigmented (III), and atrophic or hy-
                                                                 following Blaschko lines as well as a few verrucous papules.
popigmented (IV) [2,4].
                                                                 Two biopsies were performed depicting stage II and III of IP
                                                                 (Figure 2, B and C). Clinical and dermoscopic examinations
                                                                 were performed at the age of 6 months, at stage III (Figure 2,
Objectives
                                                                 A and D). As in previous stages, the affected area is devoid
Beside clinical examination, skin biopsy and IKBKG gene          of terminal hair. We observed striking linear brown to gray-
analysis are the methods used in diagnosing IP. Since these      brown dots on the light brown pigmented areas. That der-
methods are time consuming and invasive, we suggest that         moscopic image was uniform in all the examined pigmented
there is also a need for a faster and easier method as an ad-    Blaschko linear changes.
junct to clinical diagnosis.
                                                                 Case 3
                                                                 The case 1 proband mother, phototype II, presented a slightly
Methods
                                                                 visible hypopigmented 6 cm macula on the lower extremity
We clinically examined 2 female probands and one proband         (Figure 3A). Anamnesis revealed a transitory skin eruption
mother with signs of IP on the skin, which were confirmed        in childhood. The skin lesion was confirmed by biopsy as
by biopsy, and genetical examination –exons 4–10 deletion        stage IV skin finding in IP (Figure 3B). Dermoscopy revealed
on the IKBKG gene. We have used a DermLite Hybrid M              numerous very small dotted vessels present on the sur-
Dermatoscope (3 GEN) with immersion fluid and initial 10x        rounding hypo- and normally pigmented skin (Figure 3C).
magnification in a polarized mode coupled with a Nikon J3        Terminal hair was very scarce or absent on the hypopig-
camera (Nikon corporation). The study was conducted in ac-       mented skin. The surrounding normal skin had perifollicular
cordance with the Declaration of Helsinki, and approved by       depigmentation.
the Ethics Committee of University Clinical Center of Serbia        Clinical summary data for all the patients are presented
(protocol code 251/4 and date of approval May 21, 2021).         in Table 1.
Informed consent was obtained from all subjects involved in
the study.
                                                                 Conclusions
Results                                                          Since some of the stages occur in utero, the diagnosis of IP
                                                                 may be delayed or overlooked. Clinical differential diagnosis
Case 1                                                           should exclude other linear dermatoses along Blaschko lines:
The proband was 2 weeks old at the initial visit, phototype      linear and whorled nevoid hypermelanosis (both familial
II, presented with vesiculobullous lesions grouped in stripe-    and sporadic forms), hypomelanosis of Ito and lichen planus
like shapes following the lines of Blaschko (Figure 1A).         pigmentosus with Blaschkoid presentation [4,6-9].
Three months later, the proband had several verrucous               By stages, the clinical differential diagnosis of IP in the
changes (Figure 1B)], hyperpigmented maculas, and very           stage I should exclude (ie congenital herpes simplex, vari-
few vesicles. When six-months-old, there were Blaschko lin-      cella, bacterial infections, epidermolysis bullosa and bullous
ear, slightly erythematous and pigmented changes forming         pemphigoid) [4,10,11]. In the stage II of IP, dermatologists
atrophic lines with a verrucous part (Figure 1C). Biopsy was     should exclude verrucae vulgares, X-linked-dominant chon-
performed at the first and dermoscopy at all 3 clinical visits   drodysplasia punctata, linear verrucous epidermal nevus and
of the patient (Figure 1, D-H). In stage I we found solitary     lichen striatus [4,12]. Darier disease and prurigo nodularis



2                                                                    Original Article | Dermatol Pract Concept. 2022;12(3):e2022130
             Figure 1. Case 1. (A) Blaschko lines distributed lesions (2-weeks-old). (B) verrucous formation on the middle digit
             (3-months-old). Verrucous lesions were present at the same time with scarce vesicles. (C) Blaschko linear, erythem-
             atous and pigmented atrophic line with a verrucous part (6-months-old). (D) Histology: spongiosis, vesicles with
             eosinophiles, and individual apoptotic keratinocytes in the epidermis. Lymphocytes and eosinophiles were present
             focally in the superficial dermis (H&E, x 20). (E) Dermoscopy: (magnification x10) Stage I, 2-weeks-old: new
             vesicles have yellowish center and erythematous halo (arrows), while the older lesions have yellowish serocrusts
             (star) surrounded by polycyclic scalling. The vesicle in the blue circle has been biopsied. (F) Stages I and II, 2-weeks-
             old: grouped vesicles with the yellowish content (0.5-2 mm in diameter) (star) and small verrucous lesion (star).
             (G) Stage II, 3-months-old (middle digit): well developed verrucoid lesion with scarce, tiny thrombosed dotted ves-
             sels (arrows) and slightly pigmented edge. Inset: star shaped early verrucous lesion. (H) Stage II-III, 6-months-old:
             verrucous lesion with thrombosed capillaries on an erythematous and slightly pigmented background. Atrophic part
             had shiny-white linear or polygonal streaks resembling chrysalis. Note: perifollicular depigmentation (black arrows).



Original Article | Dermatol Pract Concept. 2022;12(3):e2022130                                                                           3
    Figure 2. Case 2. (A) Stage III, 6-months-old: pigmented Blaschko lines on the trunk and extremities (inset). (B) Stage
    II histology: compact hyperkeratosis, hyper-granulosis and prominent acanthosis with papillomatosis. Dyskeratotic
    cells were present in the epidermis as well as apoptotic like keratinocytes individually and in groups. Dilated blood
    vessels were visible in the dermal papillae, and lymphocytes and individual eosinophiles were present peri-vascularly.
    (H&E, x 20). (C) Stage III histology: individual cytoid bodies, and mild degree spongiosis focally in the epidermis.
    Proliferation of capillaries was visible in the papillary and superficial reticular dermis with eosinophiles as well as indi-
    vidual melanophages and free pigment. Homogenization of collagen was initiated focally in the papillary dermis (hae-
    matoxylin and eosin, x 20). (D) Stage III dermoscopy- linear gray- to gray-brown dots on the light brown pigmented
    background. The pigmentations were intermingled with normal skin and perifollicular depigmentation (stars).




                                                                     Figure 3. Case 3. (A) Stage IV, 28-years-old: the only skin
                                                                     lesion was hypopigmented macule on the lower extremity.
                                                                     (B) Stage IV histology: mildly sparse melanocytes present
                                                                     focally in the atrophic epidermis, apoptotic bodies persisted.
                                                                     Absence of pilosebaceous units, eccrine glands and melano-
                                                                     phages in the dermis. Homogenization of collagen was visible
                                                                     in the papillary dermis. Dilated capillary vessel(s) at the top of
                                                                     dermal papillae (H&E, x 20). (C) Stage IV dermoscopy (mag-
                                                                     nification 10x): perilesional and hypopigmented part had tiny
                                                                     dotted vessels, and scarce short linear vessels. Discrete, ill-
                                                                     defined white areas (stars) were observed. Inset: Note the per-
                                                                     ifollicular depigmentation of the hair in the surrounding skin.

4                                                                         Original Article | Dermatol Pract Concept. 2022;12(3):e2022130
  Table 1. Basic subject data when establishing Incontinentia pigmenti diagnosis and key laboratory
                                         and clinical findings
                                                                          Clinical findings                  IKBKG
                            Age of                                                                            exon
               Age at      proband     IP stage Skin stage(s)                                                 4-10            Skin
 Subject       onset      at 1st exam at I exam dermoscopy                        Eye            CNS        deletion     histopathology
Case 1       At birth     2 weeks        I stage       I, II, III stage     Retinopathia           -             +       Stage I
                                                                            praematuri
Case 2       At birth     1.5 months II, III stage III stage                Retinopathia Hypertonio              +       Stage II and III
                                                                            ishemica        discreta
                                                                            prolipherativa
                                                                            oculus sinister
Case 3       Unknown 28 years            IV stage      IV stage                    -               -             +       Stage IV
(mother)


may also be included. The stage III, as the hallmark stage                 changes dermoscopically observed. The reticular dermis is
of IP, one should distinguish from linear and whorled nev-                 dense, fibrous and totally devoid of pilosebaceous units and
oid hyper-melanosis and lichen planus pigmentosus with                     sweat glands, and correlates with the absence of terminal
blaschkoid presentation [6,9,13]. The stage IV should be dis-              hair observed on dermoscopy.
tinguished from hypo-melanosis of Ito, vitiligo with local-                   In dermoscopy of IP stage III, the main dermoscopic dif-
ized alopecia, different types of ectodermal dysplasia, nevus              ferential diagnosis is presented in Table 2. Linear brown to
anemicus, nevus depigmentosus, extragenital guttate lichen                 gray-brown dots are in accordance with previous 2 reports
sclerosus, achromic pityriasis versicolor, idiopathic guttate              of IP dermoscopy of pigment stage [16,17]. Perifollicular
hypomelanosis and postinflammatory hypopigmentations                       depigmentation and disruptions in the normal reticular pig-
[4,13,14]. This stage may be difficult to detect in women                  mentation of the surrounding skin have been observed. They
with light skin, the most important reason why IP diagnosis                have not been noted in any of the aforementioned conditions.
is not made until adulthood in 52% of patients [15].                       Histopathological findings of this IP stage in our study also
    There have been only 2 cases of IP dermoscopy published                correspond to literature data and dermoscopy findings. Large
so far: one with positive genetic findings, lacking a histology            deposits of free or intra-macrophagic melanin in the papillary
analysis, the other on dermoscopy on IP whorled alopecia                   dermis correspond to the gray-brown dots found on dermos-
and with no report on IKBKG gene analysis [16,17].                         copy which is suggestive for pigment incontinence [9,15,22].
    Recently, the case of 13-month-old girl with linear and                   In dermoscopy of IP stage IV, the main dermoscopic dif-
whorled hyperpigmentation preceded by vesicular lesions                    ferential diagnosis is presented in Table 2. Histopathological
(anamnestic data) on the trunk and extremities at birth was                findings of this IP stage correspond to our findings and litera-
published [18]. Genetic analysis was not performed, histology              ture data [15,23]. Homogenization of collagen in the papillary
images were not provided. In our view, this was a typical case             dermis corresponds to the white areas on the hypopigmented
of blaschkoid lichen planus pigmentosus, but not IP [19].                  skin. Numerous dotted vessels seen on dermoscopy correspond
    In dermoscopy of IP stage I, it was very easy to find a suit-          to dilated capillary vessel(s) at the top of dermal papillae.
able, small lesions for biopsy. They are clinically presented as              According to the presented findings and literature data,
seropapules and dermoscopically as yellowish seropapules                   the greatest clinical, dermoscopic and histological mimics of
with an erythematous halo. The main dermoscopic differ-                    IP are blaschkoid lichen planus pigmentosus, and more lo-
ential diagnosis is eczematous dermatitis and herpes simplex               calized, blashkoid lichen striatus [9,12,22]. Dermoscopically,
(Table 2) [20]. Tzanck smear searching for giant multinu-                  the first condition has bluish-gray dots, globules, blotches
clear cells should be performed to eliminate the suspicion on              and white lines or gray-brown dots arranged in a linear and
neonatal herpes simplex [21]. Histological inflammation cor-               reticular pattern [9,20]. The second condition has gray gran-
responds to dermoscopic erythema. Vesiculobullous forma-                   ular pigmentations arranged in a linear manner and white
tion was presented as either yellowish structures surrounded               lines [12]. Bluish gray pigmentations in both conditions cor-
by an erythematous halo or grouped vesicles or serocrusts.                 respond to melanin incontinence in the papillary dermis [9].
    In dermoscopy of IP stage II, histologically, verrucous                Furthermore, both conditions have apoptotic keratinocytes
hyperplasia, compact hyperkeratosis, acanthosis and pap-                   presented as colloid bodies and increased melanin and mela-
illomatosis correspond to the central verrucous part on                    nophages in the superficial dermis [9,12].
dermoscopy are presented in table 2. Dilated blood vessels                    This report addresses all four IP skin stages, and fol-
visible in the dermal papillae may correlate to the vessels                lows up different consecutive IP stages presented in a single

Original Article | Dermatol Pract Concept. 2022;12(3):e2022130                                                                              5
                       Table 2. Dermoscopic differential diagnosis of Incontinentia pigmenti
 Stage            Clinical diagnosis                                       Dermoscopy findings
 I          Eczematous dermatitis            Dotted vessels are distributed in clusters with yellow scales and serocrusts [20]
            Herpes simplex                   Whitish, vesicles with brown dots/globules and peripheral erythema [21]
 II         Verruca vulgaris                 Thrombosed vessels and/or hemorrhagic dots on the verrucoid part [24], but no
                                             additional findings on the surrounding skin
            Darier disease                   Central, star-like, yellowish area surrounded by a peripheral white halo [20]
            Prurigo nodularis                The “white starburst” pattern (peripheral radial white striae over a reddish-
                                             brownish background) is present; a central yellow crust is also present [20]
            Inflammatory linear verrucous    Yellow to brown “cerebriform” pattern with moderate scales and dotted
            epidermal nevus                  vessels [12]
            Lichen striatus                  Gray granular pigmentation and a white scar-like line with mild scales [12]
 III        Linear and whorled nevoid        -Numerous brownish rings, curved and streak-like lines. Also, focally distributed
            hypermelanosis                   hypopigmmented dots corresponding to perifollicular areas were found [8]
                                             - Linear or circular arrangement of streak-like pigmentations arranged in a
                                             “parallel manner” following the lines of Blaschko [25]
            Lichen planus pigmentosus        Fine/coarse, gray-blue/brown dots over a brownish background [26]
            Lichen planus pigmentosus        Discrete bluish‐gray dots, globules, blotches and rods against a brownish
            with Blaschkoid presentation     background [9]
 IV         Vitiligo                         Well-demarcated dense/glowing white area with perifollicular depigmentation
                                             (stable vitiligo) or perifollicular pigmentation (active vitiligo) [27]. Terminal hair
                                             is present with leucotrichia [28]
            Nevus depigmentosus              Reticulate pigmented spots along with the border of the normal skin were in
                                             accordance with the serrated and irregular border of nevus depigmentosus
                                             [14,28].
            Extragenital lichen sclerosus    White-yellowish structurless areas. White chrysalis-like structures, fine whitish
                                             scales [28].
            Achromic pityriasis versicolor   Diffuse hypopigmented blotches, satellite lesions. Fine scales localized in the
                                             skin furrows [28].
            Idiopathic guttate               Cloudy sky-like’’ or ‘‘cloudy’’ pattern [26]
            hypomelanosis
            Postinflammatory                 Dermoscopic findings typical of the original lesions [26].
            hypopigmentations
            Pityriasis alba                  Fairly ill-demarcated hypopigmented macules with fine scales [28].




patient. In all IP skin stages dermoscopic findings appear         References
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Original Article | Dermatol Pract Concept. 2022;12(3):e2022130                                                                               7
