Dermatology MCQ - Genetic Disorders - Incontinentia Pigmenti

A newborn female infant presents with linear streaks of vesicles and bullae on the trunk and limbs, arranged in a Blaschkoid pattern. There is peripheral eosinophilia on a complete blood count. The lesions are not pruritic. What is the most likely diagnosis, its inheritance pattern, and the most concerning potential systemic complication?

A. Incontinentia Pigmenti; X-linked dominant, lethal in males; risk of retinal detachment and blindness.
B. Epidermolysis Bullosa; autosomal recessive; risk of sepsis and squamous cell carcinoma.
C. Herpes Simplex Virus infection; acquired; risk of disseminated disease.
D. Linear IgA Disease of Childhood; autoimmune; risk of mucosal scarring.
E. Mastocytosis; sporadic; risk of anaphylaxis.

Correct Answer: A. Incontinentia Pigmenti; X-linked dominant, lethal in males; risk of retinal detachment and blindness.

Answer and Explanation

The correct answer is A. This question describes the classic Stage I (vesiculobullous stage) of Incontinentia Pigmenti (IP). The pathognomonic clues are the linear streaks of vesicles and bullae following the lines of Blaschko in a female newborn, along with peripheral eosinophilia. IP is caused by mutations in the IKBKG/NEMO gene and is X-linked dominant, meaning it is usually lethal in males in utero. Surviving males have Klinefelter syndrome (XXY) or somatic mosaicism. While IP has multi-system involvement, the most concerning and common serious complication is ocular disease, including retinal vascular ischemia and detachment, which can lead to blindness if not detected early.

Why the Other Options are Incorrect:

• B. Epidermolysis Bullosa: Blistering in EB is trauma-induced and not typically arranged in perfect linear Blaschkoid streaks from birth. It does not cause eosinophilia.

• C. Herpes Simplex Virus (HSV) infection: Neonatal HSV can present with vesicles, but they are grouped, not in linear Blaschkoid patterns, and are associated with systemic illness. Eosinophilia is not typical.

• D. Linear IgA Disease of Childhood: This autoimmune blistering disease presents with "cluster of jewels" annular vesicles/bullae, usually in older children, not neonates, and not specifically in a Blaschkoid distribution.

• E. Mastocytosis: Can present with bullae in infants (bullous mastocytosis), but lesions are usually more generalized or plaque-like, not linear and Blaschkoid. Darier's sign (urtication upon rubbing) is positive, and eosinophilia can occur, but the specific pattern is key for IP.

Additional High-Yield Information for Exams:

• Classic Four Stages (may overlap or be incomplete):

  1. Vesiculobullous Stage (Birth - 4 months): Linear, inflammatory vesicles/bullae on limbs/trunk with eosinophilia.

  2. Verrucous Stage (Months 2-6): Linear, warty, keratotic papules and plaques.

  3. Hyperpigmented Stage (Months 6 - Adult): Swirling, marbled, brown-gray hyperpigmentation in Blaschkoid patterns (the "incontinentia pigmenti" refers to pigment "dropped" into the dermis).

  4. Atrophic/Hypopigmented Stage (Adulthood): Faint, hypopigmented, atrophic linear streaks. The hyperpigmentation fades.

• Genetics: X-linked dominant, lethal in most males. Caused by mutations in the IKBKG/NEMO gene on Xq28, which encodes a modulator of the NF-κB pathway crucial for cell survival in response to stress.

• Systemic Involvement:

  • Ocular (30-70%): Retinal vascular abnormalities (avascular periphery, neovascularization), retinal detachment, strabismus, cataracts. Ophthalmologic exams are mandatory.

  • Dental (80%): Peg-shaped or conical teeth, hypodontia.

  • Neurological (30%): Seizures, intellectual disability, spasticity, CNS structural anomalies.

  • Nail: Dystrophy, pitting.

  • Breast: Hypoplasia or supernumerary nipples.

• Differential Diagnosis: The vesicular stage must be distinguished from herpes simplex, epidermolysis bullosa, and mastocytosis. The verrucous stage from linear epidermal nevi. The hyperpigmented stage from post-inflammatory hyperpigmentation and linear and whorled nevoid hypermelanosis.

• Associated Conditions & Prognosis:

  • Prognosis: Depends on systemic involvement. Many patients have only skin findings and lead normal lives. Neurological and severe ocular involvement dictate morbidity.

  • Mortality: High in utero mortality for affected males.

• Management & Rationale:

  • Rationale: Multidisciplinary surveillance from birth to detect and manage systemic complications, particularly sight-threatening retinal disease.

  • First-line/Obligatory Actions:

    1. Ophthalmology: Comprehensive eye exam at diagnosis and every 3-6 months until age 4, then every 6-12 months until puberty. Retinal ablation (laser/cryotherapy) for ischemic retina to prevent detachment.

    2. Neurology: Neurological exam and baseline brain MRI, especially if seizures develop.

    3. Dental: Early pediatric dental evaluation and care.

  • Dermatologic: The skin stages are self-limiting and require no specific treatment. The vesicles should be kept clean to prevent secondary infection.