February 2017 Case Cedars-Sinai Skip to content Close Select your preferred language English عربى 简体中文 繁體中文 فارسي עִברִית 日本語 한국어 Русский Español Tagalog English English عربى 简体中文 繁體中文 فارسي עִברִית 日本語 한국어 Русский Español Tagalog Translation is unavailable for Internet Explorer Cedars-Sinai Home 1-800-CEDARS-1 1-800-CEDARS-1 Close Find a Doctor Locations Programs & Services Health Library Patient & Visitors Community My CS-Link Education clear Go Close Academics Academics Faculty Development Community Engagement Calendar Research Research Areas Research Labs Departments & Institutes Find Clinical Trials Research Cores Research Administration Basic Science Research Clinical & Translational Research Center (CTRC) Technology & Innovations News & Breakthroughs Education Graduate Medical Education Continuing Medical Education Graduate School of Biomedical Sciences Professional Training Programs Medical Students Campus Life Office of the Dean Simulation Center Medical Library Program in the History of Medicine About Us All Education Programs Departments & Institutes Faculty Directory Anatomic and Clinical Pathology Residency Back to Anatomic and Clinical Pathology Residency Application Information Explore the Residency Training Curriculum Autopsy Pathology Rotation Bone and Soft Tissue Head and Neck Pathology Rotation Breast Pathology Rotation Cardiovascular Pathology Rotation Clinical Chemistry Rotation Coagulation Rotation Cytopathology Rotation Dermatopathology Rotation Forensic Pathology Rotation Frozen Section Rotation Gastrointestinal and Liver Pathology Genitourinary Pathology Rotation Genomic Pathology Rotation Gynecologic Pathology Rotation Hematopathology Rotation Laboratory Management Rotation Microbiology Rotation Neuropathology Rotation Pulmonary and Mediastinal Pathology Rotation Renal Pathology Rotation Transfusion Medicine Rotation Surgical Pathology Pathology Physician Scientist Training Program Residents Graduates Case of the Month Archive Publications Leadership Frequently Asked Questions February 2017 Case Authors 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. Diagnosis Incontinentia pigmenti Discussion 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. References 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 If you have questions or would like to learn more about the Anatomic and Clinical Pathology Residency Program at Cedars-Sinai, please call or send a message to Academic Program Coordinator, LeeTanya Marion-Murray. 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