A 10-year-old African American boy presented with a chief concern of severe hyperkeratosis of the hands and feet, along with mild hyperkeratosis of the perioral area and the groin.
Physical examination revealed thick, yellow, hyperkeratotic plaques encompassing the boy’s hands and feet, with constriction of the digits. Thick hyperkeratotic plaques protruded from his elbows and knees, and linear hyperpigmented plaques extended from the lower abdomen to the inguinal, scrotal, and perianal regions.
Hyperkeratosis also was present in the ear canals, the perioral area, and the base of the neck. Additionally, the boy had diffuse thinning of the scalp hair, as well as hypermobile shoulder and hip joints.
A 10-year-old boy presented with severe hyperkeratosis of the hands and feet and mild hyperkeratosis of the perioral area and groin. The child had been born prematurely at 32 weeks of gestation and had experienced poor weight gain and growth since then. The skin lesions had begun as a “diaper rash” at approximately 6 months of age, then had rapidly spread to involve the ears, neck, hands, and feet. The lesions were severely pruritic. The boy had no family history of similar skin findings.
Physical examination revealed thick, yellow, hyperkeratotic plaques encompassing the boy’s hands and feet, with constriction of the digits. Thick hyperkeratotic plaques protruded from his elbows and knees, and linear hyperpigmented plaques extended from the lower abdomen to the inguinal, scrotal, and perianal regions. Hyperkeratosis also was present in the ear canals, the perioral area, and the base of the neck. Additionally, the boy had diffuse thinning of the scalp hair and hypermobile shoulder and hip joints. The boy received a diagnosis of Olmsted syndrome.
Olmsted syndrome is a rare congenital disorder characterized by the combination of mutilating, symmetric palmoplantar keratoderma (PPK) of the palms and soles along with periorificial keratotic plaques. The keratoderma often is transgredient, with lesions extending from the palms and soles onto the dorsa of the hands and feet. Lesions often are severely pruritic, and the associated pain is variable. Other findings can include linear hyperkeratosis and other nonperiorifical keratotic lesions, onychodystrophy, diffuse alopecia or hypotrichosis, leukokeratosis, joint laxity, ocular abnormalities, ichthyotic lesions, congenital deaf-mutism, and retarded physical development.1-3
Etiology and Pathogenesis
This disorder was first described in 1927 by Harry C. Olmsted, MD.4 Approximately 73 cases have been documented since then.3 Cases have been largely sporadic, although a few familial cases have been reported with proposed autosomal dominant, autosomal recessive, or X-linked dominant inheritance patterns.5-7 There appears to be a much higher male prevalence.8,9
Previously, very little had been known about the genetics of Olmsted syndrome; gene sequencing of an affected person revealed no mutations in the genes implicated in other PPKs (including KRT1, GJB2, SLURP1, and LOR).1,7 More recently, various de novo heterozygous dominant and homozygous recessive mutations in the transient receptor potential cation channel, subfamily V, member 3 (TRPV3) gene have been identified in persons with Olmsted syndrome.10-12 Additionally, the membrane-bound transcription factor peptidase, site 2 (MBTPS2) gene has been implicated in the X-linked recessive form of the syndrome.13 The proposed pathogenesis remains unclear, but it may involve a defect in mature epidermal keratin 1 and 10 expression and the persistence of basal keratin 5 and 14, thereby resulting in excessive epithelial proliferation.3,14
Diagnosis, Prognosis, and Management
The cutaneous manifestations of Olmsted syndrome typically allow for a clinical diagnosis. Other genodermatoses featuring PPK (eg, Vohwinkel syndrome, Meleda disease, type II tyrosinemia, pachyonychia congenita, Papillon-Lefévre syndrome) should be considered in the differential, as should psoriasis inversa, chronic mucocutaneous candidiasis, and acrodermatitis enteropathica.1,5 Skin biopsy is not necessary, since results often reveal nonspecific orthohyperkeratosis, acanthosis, hypogranulosis, and chronic inflammatory dermal infiltrate.1,5,9
The clinical manifestations of Olmsted syndrome typically present in the neonatal or childhood period, with variability in disease severity.2 The course is progressive and disabling, and the mutilating nature of the PPK can progress to constriction of the digits or even autoamputation of the fingers and toes. Additionally, these patients have been found to be at increased risk for various epidermal tumors, including squamous cell cancer and malignant melanoma of involved keratotic skin.15-17
The use of various topical and oral treatments have been described in the literature, but with few consistent improvements. Topically, solution of potassium permanganate, salicylic acid, boric acid, urea, tar, retinoic acid, shale oil, corticosteroids, and prolonged soaking or wet dressings have been used with varying success.1,5 Oral retinoids, as well as systemic antihistamines, vitamin E, vitamin A, antimicrobials, and corticosteroids, have been shown to be partially effective in managing the symptoms and progression of the disease.1,18,19 In severe cases, surgical removal of the keratotic plaques with subsequent skin grafting has been attempted in order to reduce pain and improve function; however, the condition recurred in the majority of these cases after initial improvement.20
Olivia L. Quach, AB, is a student at the University of Virginia School of Medicine in Charlottesville, Virginia.
Barbara B. Wilson, MD, is an associate professor and chair of the Department of Dermatology at the University of Virginia School of Medicine in Charlottesville, Virginia.