An Bras Dermatol. 2014;89(3):486-9.
Incontinentia pigmenti or Bloch-Sulzberger syndrome: a rareX-linked genodermatosis*
Gabriela Franco Marques1 Claudio Sampieri Tonello1
Juliana Martins Prazeres Sousa1
Abstract: Incontinentia pigmenti is a rare X-linked genodermatosis that affects mainly female neonates. The firstmanifestation occurs in the early neonatal period and progresses through four stages: vesicular, verruciform,hyperpigmented and hypopigmented. Clinical features also manifest themselves through changes in the teeth,eyes, hair, central nervous system, bone structures, skeletal musculature and immune system. The authors reportthe case of a patient with cutaneous lesions and histological findings that are compatible with the vesicular stage,emphasizing the importance of early diagnosis and appropriate therapeutic management.Keywords: Genetic diseases, X-linked; Incontinentia pigmenti; Pigmentation disorders
Received on 09.07.2013.Approved by the Advisory Board and accepted for publication on 08.08.2013.* Work performed at Instituto Lauro de Souza Lima (ILSL) Bauru (SP), Brazil.
Financial Support: noneConflict of Interests: none
1 Instituto Lauro de Souza Lima (ILSL) Bauru (SP), Brazil.
2014 by Anais Brasileiros de Dermatologia
INTRODUCTIONIncontinentia pigmenti or Bloch-Sulzberger
syndrome is a rare genodermatosis, linked to X chro-mosome, of autosomal dominant character, whichaffects ectodermal and mesodermal tissues, such asskin, eyes, teeth and central nervous system.1-4 Thereare around 800 registered cases worldwide and theestimated incidence is about 1 to every 40.000 chil-dren.5
It is a disease of difficult diagnosis, which man-ifests itself during the first months of life and affectsmainly female neonates, being lethal, in most cases,when it occurs in males.4 It was described for the firsttime by Garrod in 1903, and Sulzberger was the onewho recognized the pathogenesis involved in the syn-drome, in 1926.5
The authors report a case of typical clinicalmanifestations and histopathological findings com-patible with incontinentia pigmenti in the vesicular-bullous stage, emphasizing the importance of recog-nizing this disease due to great possibility of extracu-taneous manifestations, which must be treated earlyto avoid sequelae.
CASE REPORTFemale patient, one month-old, with onset of
small papules, vesicles and linear crusts on upper andlower limbs since birth. Prenatal and deliveryoccurred without complications and the child did notpresent comorbidities.
During the dermatological exam vesiculobul-lous injuries and crusts were found in a linear dispo-sition along the lines of Blaschko, grouped, located onflexural surfaces of the upper limbs, lateral face of theright lower limb and posterior face of the left lowerlimb (Figures 1 and 2).
The anatomopathological exam revealed spon-giosis and intraepidermal vesicles containing numer-ous eosinophils (Figures 3, 4 and 5). The Tzanck testidentified no viral inclusions or bacterial colonies.
Physical exam findings and the result of com-plementary exams were compatible with the diagno-sis of Bloch-Sulzberger syndrome in the vesicular-bul-lous stage. The cutaneous lesions were treated withlow-potency topical corticoid and emollients; thechild was referred to neurological, ophthalmologicaland pediatric evaluation, which were within normal
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standards. Relatives were oriented regarding the evo-lution phases of the disease and the need of multidis-ciplinary follow-up.
After six months there was an onset of linearhypochromic lesions on the locations previouslyaffected by vesiculobullous lesions, corresponding tothe hypopigmentation stage of Bloch-Sulzberger syn-drome (Figure 6).
DISCUSSIONIncontinentia pigmenti is caused by a mutation
on the NEMO gene, located on the q28 portion of Xchromosome. It affects the skin and several systemicorgans with variable clinical expression.6
The first manifestations occur in the neonatalperiod and progress through several well-definedsteps, possibly occurring concomitantly or sequential-ly. The first stage is named vesicular or vesicular-bul-lous, characterized by vesicles and linear inflammato-ry bubbles that appear at birth or during the first twomonths and can last from weeks to months. The sec-ond stage is the verrucous, when linear verrucous
Incontinentia pigmenti or Bloch-Sulzberger syndrome: a rare X-linked genodermatosis 487
FIGURE 1: A)Vesicular-Bullous linearlesions of flexural surfa-ces of upperlimbs B)Vesicular-Bullouslesions andcrusts on lateral side oflower rightlimb
FIGURE 2: A) Vesicular-Bullous lesions on posterior face of lowerleft limb B) Lesions on lateral face of lower right limb
FIGURE 3: Anatomopathological exam: Intraepidermal vesicles(H&E, 40x)
FIGURE 4: Anatomopathological exam: Spongiosis and numerouseosinophils inside of the intraepidermal vesicle (H&E, 100x)
FIGURE 5: Anatomopathological exam: In the detail, eosinophilsinside of intraepidermal vesicle (H&E, 200x)
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hyperkeratotic plaques appear with variable dura-tion. Next the hyperpigmentation stage occurs, withthe onset of brown or bluish-gray pigmentation, dis-tributed in Blaschko lines, starting in infancy andslowly fading until it disappears in adulthood. Thelast stage is the hypopigmentation, when linearhypopigmented macules appear, with absence ofcutaneous appendixes on trunk and limbs duringadult age.4,7
In the case reported, there was the predomi-nance of vesiculobullous lesions, which allowed theclinical picture classification as vesicular-bullousstage. However, some lesions presented with a verru-cous aspect and the onset of crusts, suggesting thestart of the second stage of the disease, correspondingto the verrucous stage.
In up to 80% of the cases of incontinentia pig-menti there are associated extracutaneous manifesta-tions.2,4,5 The following structures may be affected:teeth, manifesting as anodontia, delayed dentitionand malformed teeth; retinal and corneal, microph-thalmia, cataract, iris hypoplasia, uveitis, nystagmus,strabismus and myopia changes indicate ocularinvolvement; baldness may represent hair involve-ment; central nervous system involvement may havevariable clinical presentation with convulsions,seizures, mental retardation, ischemic strokes, hydro-cephalus and anatomical abnormalities; bone struc-tures and skeletal musculature may have their devel-opment compromised and the child evolves with syn-dactyly, cranial deformities, dwarfism, supernumer-
ary ribs, hemiatrophy and shortening the legs andarms. 8,9 There may be immunological changes due todefective neutrophil chemotaxis and lymphocytefunction. Since it is a genodermatosis, there is also thepossibility of association with malignancies, such ashematological neoplasms, Wilms tumor andretinoblastoma.2,4,5
The patient in question underwent multidisci-plinary evaluation by a team composed of pediatri-cians, neurologists and ophthalmologists and up tonow no extracutaneous manifestation was identified.It is known, however, that extracutaneous involve-ment may appear late, which justifies the continuousfollow-up of these patients even after the vesicular-bullous lesions have disappeared.
Histopathology varies according to the evolution-ary stage of the disease. In the first stages it shows anincrease of eosinophils and formation of intraepidermalvesicules. In the verrucous phase hyperkeratosis, dysker-atosis, acanthosis and papillomatosis can be identified.Later, melanine deposits on the dermis withmelanophages are found in the hyperpigmentation stage.Finally, in the hypopigmentation stage discreet epider-mal atrophy and absence of annexes may be seen.4,10
Histopathological findings associated withphysical characteristics are enough to define the diag-nosis. Recently diagnostic criteria were proposed forthe syndrome, the major criterium being the typicalcutaneous alterations of one of the evolutionary phas-es of the disease. The minor criteria correspond todental, ocular, neurological, osseous and immunolog-ical alterations, as well as compatible anatomopatho-logical exam. Genetic alteration and presence of fami-ly members also affected by the disease should also betaken into consideration.10
The cutaneous manifestations do not need spe-cific treatment; spontaneous resolution of lesionsoccurs normally. Emollients and topical corticoidscan be used in the first stages of the disease.Secondary bacterial infections may occur and must betreated with antibiotics. The management of extracu-taneous manifestations must be done by a multidisci-plinary team and varies according to the affectedorgan. Furthermore, genetic counseling is also impor-tant since the disorder is of autosomal dominanttransmission.1,2,4,5
Therefore, in spite of the rarity of this patholo-gy, one must be alert for early diagnosis, recognizingthe typical cutaneous manifestations of each evolu-tionary phase of the disease, for adequate geneticcounseling and better management of extracutaneousmanifestations when these are present. q
FIGURE 6: A)Absence oflesions onupper limbsB) Residuallinearhypochromiclesions onposterior faceof left lowerlimb C)Linearhypochromiclesions onposterior faceof right lowerlimb
488 Marques GF, Tonello CS, Sousa JMP
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How to cite this article: Borges J, Cuzzi T, Mandarim-de-Lacerda CA, Manela-Azulay M. Incontinentia pigmenti orBloch-Sulzberger syndrome: a rare X-linked genodermatosis. An Bras Dermatol. 2014;89(3):486-9.
REFERENCESMhlenstdt E, Eigelshoven S, Hoff NP, Reifenberger J, Homey B, Bruch-Gerharz D.1.
Bloch-Sulzberger syndrome. Hautarzt. 2010;61:831-3.
Ehrenreich M, Tarlow MM, Godlewska-Janusz E, Schwartz RA. Incontinentia pigmen-2.
ti (Bloch-Sulzberger syndrome): a systemic disorder. Cutis. 2007;79:355-62.
Motamedi MH, Lotfi A, Azizi T, Moshref M, Farhadi S. Incontinentia pigmenti. Indian J3.
Pathol Microbiol. 2010;53:302-4.
Pereira MAC, Mesquita LAF, Budel AR, Cabral CSP, Feltrim AS. X-linked incontinentia4.
pigmenti or Bloch-Sulzberger syndrome: a case report. An Bras Dermatol.
Buinauskiene J, Buinauskaite E, Valiukeviciene S. Incontinentia pigmenti (Bloch-5.
Sulzberger syndrome) in neonates. Medicina (Kaunas). 2005;41:496-9.
Lee Y, Kim S, Kim K, Chang M. Incontinentia pigmenti in a newborn with NEMO muta-6.
tion. J Korean Med Sci. 2011;26:308-11.
Llano-Rivas I, Soler-Snchez T, Mlaga-Diguez I, Fernndez-Toral J. Incontinentia pig-7.
menti. Four patients with different clinical manifestations. An Pediatr (Barc).
Mini S, Trpinac D, Gabriel H, Gencik M, Obradovi M. Dental and oral anomalies in8.
incontinentia pigmenti: a systematic review. Clin Oral Investig. 2013;17:1-8.
Mini S, Trpinac D, Obradovi M. Systematic review of central nervous system ano-9.
malies in incontinentia pigmenti. Orphanet J Rare Dis. 2013;8:25.
Mini S, Trpinac D, Obradovi M. Incontinentia pigmenti: diagnostic criteria update.10.
Clin Genet. 2013 Jun 26.
MAILING ADDRESS:Gabriela Franco Marques Rua Alves Guimares n 518 apto. 136Pinheiros05410-000 So Paulo, SPE-mail: email@example.com
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