February 2017 Case


Andrew Siref, MD (Resident) and Wonwoo Shon, DO (Faculty)

Subject: Dermatopathology
Clinical History

The patient is a 6-day old baby girl, born at 40w2d via normal, spontaneous vaginal delivery following an uneventful pregnancy. Microcephaly and skin lesions were noted at birth. The rash appeared as scattered, erythematous, and hyperpigmented (coalescing) macules on the neck, trunk, and extremities, seemingly along the lines of Blashko.

At 30 hours of life, the patient had a witnessed seizure and was transferred to the NICU. Continuous EEG monitoring revealed frequent seizure activity. MRI of the brain demonstrated innumerable, small cortical and subcortical foci of infarction, most with associated hemorrhage.


Incontinentia pigmenti


Incontinentia pigmenti , also known as Bloch-Sulzberger disease, is a rare X-linked dominant genodermatosis caused by mutations in the IKK-γ gene (IKBKG). This condition is generally not seen in males as the trait is typically lethal in utero in the absence of a normal X-chromosome. Skin lesions are typically present in the first few weeks of life and are situated along the lines of Blashko. The linearity of the lesions is attributed to mosaicism caused by lyonization (X-inactivation). Extracutaneous abnormalities involving the teeth, bones, CNS, and eyes are common and sometimes can present as the dominant clinical features of the disorder. Seizures and microcephaly are among the most common findings involving the CNS. Peripheral eosinophilia is also a common finding.

Incontinentia pigmenti is characterized by four stages: vesicular, verrucous, hyperpigmented, and hypopigmented. However, stages may overlap and not all patients express each stage. Subungual tumors can also occur in the late phase of incontinentia pigmenti. These tumors are very painful and frequently involve multiple digits.

Histopathologic Features
Differential Diagnoses

Vesicular stage

Eosinophilic spongiosis and intraepidermal vesicle formation with dyskeratosis and mixed dermal inflammatory infiltrate

Hypersensitivity-type reaction (i.e., drug eruption), erythema toxicum neonatorum, autoimmune blistering disorder

Verrucous stage

Verruciform epidermal hyperplasia and dyskeratosis with mixed dermal inflammatory infiltrate

Epidermal nevus

Hyperpigmented stage

Papillary dermal pigment (melanin) incontinence

Linear and whorled nevoid hypermelanosis, postinflammatory hyperpigmentation

Hypopigmented stage

Epidermal atrophy and papillary dermal pigment (melanin) incontinence with decreased/absence of cutaneous adnexal structures

Hypomelanosis of Ito, postinflammatory hypopigmentation

Subungual tumor

Essentially indistinguishable from subungual keratoacanthoma

Subungual keratoacanthoma

Clinical Wrap-Up

Sequencing of IKBKG in this patient revealed a c.766C>T mutation which was present in some - but not all - cells, consistent with somatic mosaicism. The presence of this variant is consistent with a diagnosis of incontinentia pigmenti.


1. Patterson, James W., MD, FACP, FAAD. Weedon's Skin Pathology, 4th edition. London, UK: Churchill Livingstone (Elsevier Limited); 2016.

2. James, William D., MD, Elston, Dirk M., MD, and Berger, Timothy G., MD. Andrews' Diseases of the Skin, 12th edition. Philadelphia, PA: Elsevier; 2011.

3. Busam, Klaus J., MD and Goldblum, John R., MD, FACP, FASCP, FACG. Dermatopathology, 2nd edition. Philadelphia, PA: Saunders, an imprint of Elsevier Inc.; 2016.

Have Questions or Need Help?

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