Olmsted Syndrome

What Is It, Causes, Signs, and More

Author: Lily Guo, MD

Editor: Alyssa Haag, MD

Editor: Emily Miao, MD, PharmD

Editor: Kelsey LaFayette, DNP, ARNP, FNP-C

Illustrator: Jannat Day

Copyeditor: David G. Walker

Modified: Jan 06, 2025

What is Olmsted syndrome?

Olmsted syndrome, also known as mutilating congenital palmoplantar and perioral keratoderma, is an ultra-rare disorder that results in keratoderma, or marked thickening of the epidermis of the skin on the bilateral palms, soles, and around the mouth with severe pruritus. It was named after H. C. Olmsted, the individual who originally described the condition in 1927. Approximately 73 cases have been reported in the literature worldwide. Olmsted syndrome is a genodermatosis (i.e., hereditary skin disease) that belongs to the heterogeneous group of keratin disorders referred to as palmoplantar keratoderma (PPK). When keratoderma is present around the digits of hands, it can lead to limited mobility, constriction, or spontaneous amputation.

An infographic detailing the background, causes, risk factors, signs and symptoms, diagnosis, and treatment of Olmsted syndrome.

What causes Olmsted syndrome?

Olmsted syndrome is thought to be due to gain-of-function mutations in the transient receptor potential vanilloid-3 (TRPV3), which results in increased keratinocyte apoptosis and hyperkeratosis, or thickening of the stratum corneum. Changes in the membrane-bound transcription factor protease site 2 (MBTPS2) gene and defects in the expression of specific types of mature epidermal keratin, specifically types 1 and 10, have also been implicated in disease; however, exact mechanisms remain unclear. Most cases of Olmsted syndrome occur sporadically (i.e., de novo); however, familial cases with different modes of inheritance have been reported. There has been a familial case that was possibly due to autosomal dominant transmission, a case of X-linked dominant inheritance in two monozygotic male twins, and a case of autosomal recessive inheritance of disease.

What are the signs and symptoms of Olmsted syndrome?

The signs and symptoms of Olmsted syndrome include thickening of the skin around the mouth and the development of perioral and perinasal keratotic plaques; hyperkeratosis of the palms and soles of the feet; and mutilating, constricting bands forming around the digits. The hyperkeratotic plaques are classically sharply marginated, fissured, and yellowish in color with associated subungual hyperkeratosis (i.e., chalky build-up under the nail). Olmsted syndrome can present with severe pruritus and pain in the affected areas that can be debilitating. While these are the most common symptoms and are hallmarks of diagnosis, some individuals may also have macerated keratotic plaques around the eyes, ears, navel, genital and anal regions, and on the thighs, arms, elbows, knees, and intertriginous folds.

Hair and nail abnormalities can also be seen in Olmsted syndrome. For example, onychodystrophy (i.e., nail dystrophy) as well as hypotrichosis (i.e., decreased hair growth) of the scalp, eyebrows, and eyelashes have been reported. Sweating abnormalities, including both hyperhidrosis and anhidrosis of the palms and soles, may be present. Disorders of the eye have been reported as well, including chronic blepharitis (i.e., inflammation of the eyelids), corneal epithelial dysplasia, and corneal opacities. Other findings include oral lesions, abnormal dentition, short stature, bone abnormalities, and high-frequency hearing loss.

The condition is often present at birth or begins in early childhood and has a slow but progressive course. The perioral lesions may improve with age. The keratoderma of the distal extremities typically becomes extremely thick and may interfere with the use of one's hands and walking. Individuals may therefore require assistive devices, such as wheelchairs. Fissuring can also occur around the fingers and toes. As the fissured skin heals, it may leave behind a band of constrictive tissue, resulting in autoamputation of the digits. The compromised skin barrier can predispose the individual to recurrent bacterial or candidal infection. Furthermore, Olmsted syndrome has been linked to increased rates of malignancy in keratotic areas, including verrucous carcinoma, a form of squamous cell carcinoma; epithelioma cuniculatum; and malignant melanoma. The condition affects all sexes; however, it is more common in those assigned male at birth.

How is Olmsted syndrome diagnosed?

Diagnosis of Olmsted syndrome is based on clinical symptoms, including symmetrical keratoderma involvement of the palms and soles and symmetrical periorificial keratotic plaques. In most cases, the clinical presentation is typically sufficient for diagnosis; however, reports have shown there are some individuals with only partial cutaneous expression of Olmsted syndrome, resulting in a mild presentation of the condition. In these cases, genetic testing looking for mutations in TRPV3 or MBTPS2 can be helpful. Unfortunately, histopathology has limited utility for diagnosis as biopsies show nonspecific findings of epidermal hyperplasia, incomplete maturation of keratinocytes (i.e., parakeratosis), and inflammatory infiltration in the upper dermis. Oftentimes, a referral to a dermatologist or a pediatric dermatologist may be necessary to confirm the diagnosis and differentiate Olmsted syndrome from other conditions.

How is Olmsted syndrome treated?

There is no cure for Olmsted syndrome, and therefore, treatment is often focused on managing the symptoms of hyperkeratosis, including pain and itching. Nonsteroidal anti-inflammatory drugs (NSAIDs), topical lidocaine, and soaking of lesions in cold water can help control pain. Other goals of treatment include reducing the likelihood of fissuring and infection and decreasing the thickness of the plaques. Topical treatments, including keratolytic medications, such as urea, salicylic acid, ammonium lactate to decrease skin thickness; corticosteroids to reduce inflammation; retinoids to inhibit keratinocyte proliferation; antimicrobials (e.g., mupirocin) and emollients to decrease loss of moisture from the skin, have all been tried with poor-to-moderate improvement in symptoms.

Using wet dressings to occlude the topical agents and soaking the affected areas in lukewarm water prior to applying topical treatments may increase penetration of the medication. In some cases, a provider may also pare down the affected areas with a sterile instrument, such as a blade, prior to applying topical medication. In addition to topical treatment, oral retinoids and steroids have been used to treat Olmsted syndrome. Oral antihistamines and vitamins E and A, have also been used anecdotally with no consistent benefits. Currently, a medication used for cancer, erlotinib hydrochloride, is being studied at lower doses for the treatment of Olmsted syndrome. Lastly, excisions of PPK have also been performed, but lesions typically recur following initial improvement. The treatment of Olmsted syndrome involves an interdisciplinary team consisting of dermatologists, pain management, geneticist, dentists, ophthalmology, orthopedic surgery, and psychiatry given the clinical variability in presentation.

What are the most important facts to know about Olmsted syndrome?

Olmsted syndrome refers to a rare genodermatosis that is characterized by thickening of the epidermis, or keratoderma, of the bilateral palms, soles, and around the mouth. This can lead to difficulties grasping and walking as well as fissuring of the skin, resulting in autoamputation of digits. Most cases of Olmsted syndrome occur sporadically; however, autosomal dominant, autosomal recessive, and X-linked cases have been reported. Diagnosis can be made based on clinical presentation and is confirmed with genetic testing. Treatment is largely supportive; aims to reduce the symptoms of pruritus and pain; and includes topical emollients, keratolytics, and corticosteroids. Currently, there is no cure; however, oncogenic drugs are undergoing research as a more effective treatment of Olmsted syndrome.

References

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Atherton DJ, Sutton C, Jones BM. Mutilating palmoplantar keratoderma with periorificial keratotic plaques (Olmsted's syndrome). Br J Dermatol. 1990;122:245–52.

Cambiaghi S, Tadini G, Barbareschi M, Caputo R. Olmsted syndrome in twins. Arch Dermatol. 1995;131:738–9.

Kress DW, Seraly MP, Falo L, Kim B, Jegasothy BV, Cohen B. Olmsted syndrome: Case report and identification of a keratin abnormality. Arch Dermatol. 1996;132:797–800

Lin Z, Chen Q, Lee M, Cao X, Zhang J, Ma D, et al. Exome sequencing reveals mutations in TRPV3 as a cause of Olmsted syndrome. Am J Hum Genet. 2012;90:558–64.

Olmsted HC. Keratoderma palmaris et plantaris congenitalis: Report of a case showing associated lesions of unusual location. Am J Dis Child. 1927;33:757–64.

Poulin Y, Perry HO, Muller SA. Olmsted syndrome–congenital palmoplantar and periorificial keratoderma. J Am Acad Dermatol. 1984;10:600–10.

Ruiz-Maldonado R, Lozano-Ferral N. Mutilating palmo-plantar hyperkeratosis with alopecia and erythematous inguinal and perianal lesions. Int J Dermatol. 1972;11:31–5.

Yoshizaki Y, Kanki H, Ueda T, Ichihashi M, Ueda M. A further case of plantar squamous cell carcinoma arising in Olmsted syndrome. Br J Dermatol. 2001;145:685–6.