Random Dermatology MCQ - Ichthyosis Hystrix

A newborn is noted to have severe, generalized, spiky, hyperkeratotic plaques that are brown-black in color, giving the skin a "porcupine" or "hedgehog" appearance. The plaques are present at birth and are associated with contractures of the limbs. The infant develops rapidly worsening respiratory distress. The most likely diagnosis and the expected inheritance pattern is:

A. Harlequin ichthyosis, autosomal recessive.
B. Lamellar ichthyosis, autosomal recessive.
C. Ichthyosis hystrix of Curth-Macklin, autosomal dominant.
D. Epidermolytic ichthyosis (bullous congenital ichthyosiform erythroderma), autosomal dominant.
E. Netherton syndrome, autosomal recessive.

Correct Answer: C. Ichthyosis hystrix of Curth-Macklin, autosomal dominant.

Answer and Explanation

The correct answer is C. This question describes an extremely severe presentation, most consistent with a form of ichthyosis hystrix, specifically the Curth-Macklin type. The key terms are "spiky," "porcupine-like," and brown-black hyperkeratotic plaques present at birth, which are classic descriptors for this rare disorder. The association with limb contractures (due to severe skin restriction) and the rapid onset of respiratory distress (which can occur from restricted chest wall movement or aspiration) indicates a life-threatening neonatal presentation. Ichthyosis hystrix of Curth-Macklin is caused by mutations in the KRT1 gene and follows an autosomal dominant inheritance pattern, though many cases are due to de novo mutations.

Why the Other Options are Incorrect:

• A. Harlequin ichthyosis: This presents with massive, thick, armor-like plates of scale with deep fissures, severe ectropion, and eclabium. While life-threatening, the scale is described as plate-like rather than spiny or porcupine-like.

• B. Lamellar ichthyosis: This presents as a collodion baby at birth, which then sheds to reveal large, dark, plate-like scales over the entire body. It is not typically described as having a spiny, porcupine appearance.

• D. Epidermolytic ichthyosis (EI): This presents at birth with widespread blistering and erosions (due to epidermolysis) on an erythematous base, which later evolves into a warty, hyperkeratotic pattern. The initial presentation is blistering, not generalized spiky hyperkeratosis without blistering.

• E. Netherton syndrome: This presents with congenital erythroderma and scaling, along with bamboo hair (trichorrhexis invaginata). The scaling is fine and bran-like, not massive and spiky.

Additional High-Yield Information for Exams:

• Pathogenesis & Genetics: Ichthyosis hystrix Curth-Macklin is caused by specific mutations in the KRT1 gene that affect the tail domain of keratin 1. This leads to a unique histopathologic finding: perinuclear shells of abnormal keratin within suprabasal keratinocytes, visible on electron microscopy. It is autosomal dominant.

• Clinical Spectrum: The severity can vary dramatically. The description in the question represents the most severe, life-threatening neonatal form. Milder cases may present later in childhood with milder, verrucous hyperkeratosis.

• Histopathology (Light Microscopy): Shows massive orthohyperkeratosis, acanthosis, and papillomatosis. The distinctive feature is epidermolytic hyperkeratosis confined to the upper stratum spinosum and granulosum (unlike widespread epidermolysis in Epidermolytic Ichthyosis). The basal layer is spared.

• Differential Diagnosis: The main differential is other severe congenital ichthyoses, particularly:

  • Harlequin Ichthyosis: Plate-like armor.

  • Epidermolytic Ichthyosis: Blistering at birth.

  • Ichthyosis Hystrix Gravior (of Lambert): An even rarer, possibly historical variant described as having similar features.

• Associated Conditions & Prognosis:

  • Neonatal Course: The severe neonatal form carries a high mortality risk due to respiratory compromise, sepsis, and electrolyte imbalance from a compromised skin barrier.

  • Long-term: Survivors have a chronic, severe ichthyosis with significant morbidity from contractures, infection, and heat intolerance. The hyperkeratosis can be disfiguring and debilitating.

• Management & Rationale:

  • Rationale: In the neonatal period, management is an intensive care emergency focusing on stabilization of the skin barrier, temperature, hydration, and respiration. Long-term management aims to reduce scale and prevent complications.

  • Neonatal Intensive Care: Admission to a NICU. Management includes:

    • High-humidity incubator.

    • Prophylactic antibiotics (due to high infection risk).

    • Meticulous skin care with frequent application of bland emollients/ointments.

    • Respiratory support as needed.

    • Nutritional support (increased caloric needs).

  • Long-term Dermatologic Care: Systemic retinoids (acitretin, isotretinoin) are often the mainstay of therapy to reduce hyperkeratosis. Must be used with caution due to side effects. Topical keratolytics (urea, lactic acid, salicylic acid) and regular bathing/debridement are essential.