incontinentia pigmenti

What Are These Streaks and Swirls on an Infant Girl’s Limbs?

Alexander K. C. Leung, MD—Series Editor, and Benjamin Barankin, MD

A 5-month-old girl was born to 28-year-old gravida 4 para 1 mother at 38 weeks’ gestation, following an uncomplicated pregnancy and a normal vaginal delivery. Her father was a 30-year-old healthy man, and the parents were nonconsanguineous. The girl’s birth weight was 3.1 kg, and her length was 50 cm. As reported by her mother, erythematous papules and vesicles were noted on the child’s upper and lower limbs in the immediate neonatal period. The rash transformed into verrucous streaks in a linear and swirling pattern at 2 months of age. Subsequently, at 4 months of age, hyperpigmented streaks and swirls were noted. There was no family history of similar skin lesions. Ten days prior to presentation, the infant had a seizure unassociated with fever.

On physical examination, vital signs were normal. There were streaks and swirls of brown pigmentation along the lines of Blaschko on the upper limbs (Figure 1) and lower limbs (Figure 2). Patchy alopecia on the vertex was also noted. The rest of the examination was unremarkable.  


What’s your diagnosis? 

(Answer and discussion are on the next page.)

ANSWER: Incontinentia pigmenti 

Incontinentia pigmenti, also known as Bloch-Sulzberger syndrome, is an X-linked dominant neurocutaneous genodermatosis characterized by linear cutaneous lesions along the lines of Blaschko and often accompanied by neurologic, ocular, dental, and skeletal abnormalities.1 The condition was first described in 1908 by Garrod.2 Subsequently, Bloch3 and Sulzberger4 delineated the condition in 1926 and 1928, respectively, and the condition now also bears their names. The term “incontinentia pigmenti” was coined by Bloch based on the observation of accumulation of melanin in the deep dermis as a free pigment or melanophages with resultant incontinence of epidermal pigment.3


The prevalence of incontinentia pigmenti is estimated at 0.7 per 100,000 live births.5 Approximately 98% of affected patients are females.6 The majority of affected males die in utero.1 The condition can occur in living males in the setting of postzygotic mosaicism, hypomorphic mutations, or in association with Klinefelter syndrome (47, XXY).5,7-10 Most cases of incontinentia pigmenti are sporadic.5 The condition is familial in approximately 20% of cases; there is no ethnic predominance.11 Incontinentia pigmenti usually presents in the neonatal period with approximately 50% of cases presenting at birth.12 Approximately 96% of cases present by 6 weeks of age.13


Incontinentia pigmenti is inherited as an X-linked dominant trait. The condition is caused by mutations in the IKBKG/NEMO gene (inhibitor of kB light polypeptide gene enhancer in B cells, kinase gamma/nuclear factor kB essential modulator) that has been mapped to Xq28.5,14 The gene is crucial for the regulation of tumor necrosis factor-induced apoptosis; mutation of the gene results in cells susceptible to apoptosis from intrinsic factors.14 Lyonization of the X chromosome accounts for the reticular or whorled cutaneous pattern pathognomonic for incontinentia pigmenti.


Histopathology of the lesion shows epidermal spongiosis, intraepidermal vesicles filled with eosinophils, and dyskeratotic keratinocytes during the vesicular stage; hyperkeratosis, acanthosis, and papillomatosis in the verrucous stage; melanin deposits in the dermis as free pigment or in aggregates of melanophages and incontinence of epidermal pigment during the hyperpigmented stage; and discreet epidermal atrophy and lack of eccrine glands in the hypopigmented or atrophic stage.12,13,15,16

Clinical Manifestations

In general, clinical manifestations are more exuberant in sporadic than in familial cases.14 The cutaneous manifestations of incontinentia pigmenti usually progress through 4 successive but often overlapping stages; the lesions are distributed along the lines of Blaschko.1,9 Sites of predilection include the lower limbs, followed by the upper limbs, and trunk.14 The face is usually spared.8 

The first stage (the vesicular stage) presents with papules and vesicles on an erythematous base appearing in crops beginning at birth or within the first few weeks of life, with each crop lasting 1 to 2 weeks.12 The vesicles can become pustular and bullous.13 

The second stage (the verrucous/hyperkeratotic stage) presents with verrucous streaks consisting of hyperkeratotic warty papules or plaques in linear or swirling pattern.12 This phase usually appears within 2 to 6 weeks and disappears by 6 months of age.13,16 

The third stage (the hyperpigmented stage) presents with slate grey or brown hyperpigmented streaks, flecks, swirls, or whorls in a “marble cake pattern,” lending to the name of this disorder.12 The location of these lesions does not always correspond to areas of prior cutaneous involvement during earlier stages.6,16 The hyperpigmented stage is the most characteristic stage for incontinentia pigmenti and is present in approximately 98% of patients. The hyperpigmented stage usually fades by adolescence.1,16 

The fourth stage (the hypopigmented/atrophic stage) presents with hypopigmentation, hairless anhidrotic patches, atrophy, and scarring. This stage typically takes many years to develop.1,9 Only 28% of patients have lesions in the fourth stage, and these are lesions that might persist into adulthood.16 It is important to note that some of the stages might develop in utero.1 Also, not all patients experience all 4 stages, and overlapping of stages is common.1,17 Thus, absence of certain stages does not exclude the diagnosis of incontinentia pigmenti.9

Other cutaneous abnormalities include patchy alopecia, thin and sparse hair, nail dystrophy, onychogryphosis, subungual fibroma, and woolly-hair nevus.12,14,17 In approximately 80% of cases, there are associated extracutaneous manifestations.15 These include central nervous system abnormalities (eg, spastic paralysis, cerebral atrophy, microcephaly, hydrocephaly, psychomotor retardation, cerebellar ataxia),5,10 ocular abnormalities (eg, strabismus, cataracts, nystagmus, microphthalmia, iris hypoplasia, optic nerve atrophy, retinal neovascularization, retinal detachment),10,14 dental abnormalities (eg, delayed primary/permanent dentition, hypodontia/anodontia, microdentia, pegged/conical teeth, impaction),1,14,17 skeletal abnormalities (eg, microcephaly, supernumerary ribs, syndactyly, hemiatrophy, shortening of limbs),13 and breast abnormalities (eg, supernumerary nipples, nipple/breast hypoplasia/aplasia).14 


The diagnosis is usually clinical based on the characteristic cutaneous alterations of one or more of the evolutionary stages of the disease (major criteria) as well as other extracutaneous manifestations (minor criteria). With a positive family history, the presence of any major criterion strongly supports the diagnosis.14 In the absence of a family history, the presence of at least one major criterion is required while the presence of minor criteria supports the diagnosis.14 Referral to a dermatologist should be considered if the diagnosis is in doubt. Molecular-based diagnosis can be achieved by demonstrating mutations in the IKBKG/NEMO gene that occur in 85% of affected patients.12 

Differential Diagnosis 

The main differential diagnosis includes linear and whorled nevoid hypermelanosis, hypomelanosis of Ito, and linear epidermal nevus. Linear and whorled nevoid hypermelanosis is characterized by linear streaks and swirls of macular hyperpigmentation in a reticulate pattern along the lines of Blaschko without any preceding inflammatory or verruciform lesions.18 Sites of predilection include the trunk and extremities. The hyperpigmentation usually appears within a few weeks of birth. The lesion tends to progress for 1 to 2 years before stabilizing and usually persists indefinitely. 

In hypomelanosis of Ito, the skin lesion consists of seemingly bizarre, macular, hypopigmented streaks, stripes, whorls, and patches that conform to the lines of Blaschko.19 The lesions always involve more than 2 body segments. 

Linear epidermal nevus typically presents as an asymptomatic, linear plaque consisting of well-circumscribed, discrete or confluent, pebbly, skin-colored, yellow or brown, closely-set or coalescing, noninflammatory papules.20 The lesion usually occurs on the trunk, neck, and extremity and follows Blaschko lines. The condition is often present at birth but might arise during the first year of life. The nevus may have a white and macerated appearance at birth. The lesion tends to become thicker, verrucous, and hyperpigmented over time, particularly around the time of puberty.20 The lesion grows slowly during childhood, but by adolescence it usually stops growing and does not extend any further. 

Depending on the stage, other differential diagnoses include erythema toxicum neonatorum, zosteriform herpes simplex, varicella, bullous impetigo, allergic contact dermatitis, mastocytosis, epidermolysis bullosa, lichen striatus, inflammatory linear verrucous epidermal nevus, linear lichen planus, linear psoriasis, phytophotodermatitis, erythema ab igne, nevus sebaceous, molluscum contagiosum, verruca vulgaris, and vitiligo.21


The lesion can be aesthetically unappealing. Children with incontinentia pigmenti are at increased risk of pulmonary arterial hypertension,22 seizures,6 ischemic cerebrovascular accidents,6 recurrent infections,5 autoimmune diseases,14 and malignancies (eg, chronic myelogenous leukemia, Wilms tumor, retinoblastoma).1 Affected women have an increased risk of spontaneous abortion.17


In general, the prognosis is good with poor outcomes related to any underlying neurologic, ophthalmologic, dental, or skeletal complications.23


There is no effective treatment for this condition. Therapy is mainly symptomatic and supportive. Management requires a multidisciplinary approach and may require care from a pediatrician, dermatologist, dentist, geneticist, ophthalmologist, orthopedic surgeon, neurologist, and neurosurgeon depending on the specific manifestations that need to be addressed.  

Alexander K. C. Leung, MD, is a clinical professor of pediatrics at the University of Calgary and a pediatric consultant at the Alberta Children’s Hospital in Calgary, Alberta, Canada. 

Benjamin Barankin, MD, is a dermatologist and the medical director and founder of the Toronto Dermatology Centre in Toronto, Ontario, Canada.


1. Leung AKC, Kao CP, Robson WL. Incontinentia pigmenti in an infant.

J Pediatr. 2006;149(1):138.

2. Garrod AE. Peculiar pigmentation of the skin in an infant. Trans Clin Soc London. 1906;39:216.

3. Bloch B. Krunkendemonstrationen aus der Dermatologischen Klinik Zurich. 1. Eigentumliche bisher nicht beschriebene Pigmentaffektion (Incontinentia pigmenti). Schweiz Med Wschr. 1926;7:404-405.

4. Sulzberger MB. Uber eine bisher nicht beschriebene congenital Pigmentanomalie (incontinentia pigmenti). Arch Dermatol Syphil. 1928;154:19-32.

5. Fusco F, Paciolla M, Conte MI, et al. Incontinentia pigmenti: report on data from 2000 to 2013. Orphanet J Rare Dis. 2014;9:93.

6. Poziomczyk CS, Recuero JK, Bringhenti L, et al. Incontinentia pigmenti. An Bras Dermatol. 2014;89(1):26-36.

7. Afshar H, Daneshpazhooh A, Kiani A, Aref P, Baniameri Z. Abnormal dentition in a boy with incontinentia pigmenti: case report. J Dent. (Tehran) 2012;9(3):267-270.

8. Gonzalez EM, DeKlotz CC, Eichenfield LF. A 6-day-old male infant with linear band of skin-colored papules. JAMA Pediatr. 2014;168(9):859-860. 

9. Mullan E, Barbarian M, Trakadis Y, Moroz B. Incontinentia pigmenti in an XY boy: case report and review of the literature. J Cutan Med Surg. 2014;18(2):119-122.

10. Wright TS. The genodermatosis. UpToDate. Updated February 22, 2016. Accessed July 24, 2016.

11. Welch JL, Jimenez HL, Allen SE. Pediatric rash: dermatologic manifestations of incontinentia pigmenti. J Emerg Med. 2013;45(2):e41-e43.

12. Pielop JA. Vesiculobullous and pustular lesions in the newborn. UpToDate. Updated March 16, 2016. Accessed July 24, 2016.

13. Poliak N, Le A, Rainey A. Reticulated, hyperchromic rash in a striated pattern mimicking atopic dermatitis and fungal infection in a 2-month-old female: a case of incontinentia pigmenti. Case Rep Pediatr. 2016;2016:9512627. doi:10.1155/2016/9512627.

14. Poziomczyk CS, Bonamigo RR, Maria FDS, Zen PRG, Kiszewski AE. Clinical study of 20 patients with incontinentia pigmenti. Int J Dermatol. 2016;55(2):e87-e93.

15. Marques GF, Tonello CS, Sousa JMP. Incontinentia pigmenti or Bloch-Sulzberger syndrome: a rare X-linked genodermatosis. An Bras Dermatol. 2014;89(3):486-489.

16. Jessup CJ, Morgan SC, Cohen LM. Incontinentia pigmenti: treatment of IP with topical tacrolimus. J Drugs Dermatol. 2009;8(10):944-946.

17. Fryssira H, Kakourou T, Valari M, Stefanaki K, Amenta S, Kanavakis E. Incontinentia pigmenti revisited. A novel nonsense mutation of IKBKG gene. Acta Paediatr. 2011;1001(1):128-133.

18. Leung AKC, Adams SP. Hyperpigmented lesion following Blaschko lines. Consultant Pediatrician. 2012;11:373-374.

19. Leung AKC, Robson WL. Index of suspicion: hypomelanosis of Ito. Pediatr Rev. 2007;28(5):193-197.

20. Leung AKC, Barankin B. What is this asymptomatic linear eruption behind a girl’s right ear? Consultant Pediatrician. 2016;15(3):117-121.

21. Kruse LL. Differential diagnosis of linear eruptions in children. Pediatr Ann. 2015;44(8):e194-e198.

22. Yasuda K, Minami N, Yoshikawa Y, Fukuda S, Yamaguchi S. Fatal pulmonary arterial hypertension in an infant girl with incontinentia pigmenti. Pediatr Int. 2016;58(5):394-396.

23. Shah L, Balakumar G. A persistent newborn rash. Pediatr Rev. 2007;28(11):429-432.