Background
In 1929, Vohwinkel first described this syndrome in a 24-year-old woman who, since age 2 years, had a diffuse honeycombed palmar and plantar keratosis, in addition to distal interphalangeal creases. The constrictions ultimately led to autoamputation. The daughter of this patient experienced similar clinical lesions.
Pseudoainhum is the autoamputation of any digit secondary to keratodermas and other causes. In contrast, ainhum is the posttraumatic or postinfectious development of constricting bands of the digits resulting in autoamputation. Several categories can be distinguished, as follows:
Ainhum (dactylolysis spontanea): Ainhum is spontaneous autoamputation of the fifth toe, predominantly affecting blacks in tropical climates. This form most likely is posttraumatic or postinfectious in nature and is uncommon in the United States.
Congenital annular constricting bands
Autoamputation of traumatic origin, including self-mutilation and mechanical factors, frostbite, and burns
Pathophysiology
Vohwinkel syndrome belongs to the group of palmoplantar keratodermas. It is considered to have an autosomal dominant inheritance, although sporadic cases[1, 2] and a case of probable autosomal recessive inheritance[3] have also been described.
Connexins 26, 30, 30.3, 31, and 43 are related to cutaneous diseases associated with multiple organ involvement. Mutations in connexin 26 are linked to Vohwinkel syndrome, keratitis-ichthyosis deafness and hystrixlike ichthyosis deafness syndromes, palmoplantar keratoderma with deafness, deafness with Clouston-like phenotype, and Bart-Pumphrey syndrome.[4]
Two mutations of the epidermal differentiation complex have been identified in Vohwinkel syndrome.
One is a missense mutation of the GJB2 gene coding connexin-26, a gap junction protein.[5, 6, 7] This mutation on chromosome 13 is associated with the classic (hearing loss–associated) Vohwinkel syndrome. Connexins are building blocks of gap junctions that are plasma membrane complexes facilitating and regulating the passage of small molecules between cells. Several other rare mutations have also been described.
Another mutation is an insertional mutation of the loricrin gene on the epidermal differentiation complex on 1q21. This protein plays a major function in the formation of the cornified cell envelope. Sequential deposition of altered loricrin during terminal differentiation of keratinocytes and other components causes an increase in envelope thickness and rigidity. A phenotype associated with ichthyosis and not deafness is observed.
An ichthyotic variant has been described with a 730insG mutation.[8]
Etiology
Causes of the two types are as follows:
Epidemiology
Frequency
The syndrome is rare, with fewer than 30 cases reported.
Race
No racial predominance is noted.
Sex
No sex predominance is reported.
Age
This syndrome usually manifests between infancy and early childhood.
Prognosis
The prognosis is good as long as medications are used. Patients with this syndrome may have a normal life span, persistent keratoderma, potential loss of digits, and hearing loss in the classic variant. Prenatal diagnosis by DNA analysis is possible if the gene defect is known.[9]
Patient Education
Tailor patient education to the course and complications.
History
The classic skin lesions develop at an early age. Explore the family history for abnormalities suggestive of Vohwinkel syndrome.
Physical Examination
The classic triad is as follows:
Diffuse palmoplantar keratoderma in a honeycombed pattern
Constricting bands of the digits with autoamputation (pseudoainhum)
Starfish-shaped hyperkeratotic plaques on the dorsum of the hands and feet, elbows, and knees (In addition, linear hyperkeratoses may be observed on the elbows and knees.)
Note the images below:
View Image | Starfish-shaped plaques. |
View Image | Palmar hyperkeratosis. |
View Image | Pseudoainhum. |
Rare associated findings include scarring alopecia and nonprogressive sensorineural hearing loss at high frequencies (classic variant).
A case report of two siblings described a probable new variant of Vohwinkel syndrome with congenital hypotrichosis.[10] Cases with mental retardation[11] and an ichthyosiform presentation[12] have also been described.
Complications
Complications can include loss of digit(s) with functional impairment of the limb and hearing loss.
Imaging Studies
Obtain radiographs of the hands and feet to detect abnormalities of the underlying bones. Use craniofacial imaging studies if clinical findings justify them.
Other Tests
Audiometry is suggested to evaluate the nature and extent of hearing loss and for eventual follow-up.
Procedures
No invasive diagnostic procedures are routinely indicated.
Histologic Findings
Histologic findings are nonspecific. The constricting bands consist of fibrous connective tissue resembling scars.
Medical Care
Tailor medical care to individual defects or functional impairment of the limbs or hearing.
Surgical Care
Surgical release of the constriction bands is used to preserve the digits (eg, Z-plasty, other methods for relaxing scars).
Consultations
Consultation with the following specialists may be needed:
Surgeon - If any deformities of the fingers or craniofacial features are present
Audiologist and speech therapist - If hearing loss is noted
Other specialists - As indicated by clinical abnormalities
Genetic counselor - Advisable to discuss risk of the offspring being affected by the syndrome
Diet
No dietary interventions are indicated for treatment. Oral bioavailability of retinoids is enhanced with food intake.
Activity
Activity is unrestricted.
Long-Term Monitoring
Regular follow-up by a dermatologist is recommended. Refer the patient to a surgeon if pseudoainhum develops. Further care and laboratory testing or radiography depend on the treatment selected, course, and complications. Audiologists and speech therapists may be referred on an individual basis.
Medication Summary
Because of the rarity of this syndrome, all treatment options are based on sporadic experience and are off-label uses. Topical treatment is usually inadequate, although keratolytics (ie, salicylates, urea) and retinoids can alleviate keratoderma. Systemic retinoids can reverse both the keratoderma and pseudoainhum; however, relapse is the rule upon discontinuation of treatment.[13] If topical retinoids are used in women with childbearing potential, inform patients about teratogenicity and apply current guidelines. Low-dose tretinoin was reported to prevent digital amputation.[14]
Isotretinoin (Accutane)
Clinical Context:
Isotretinoin is an oral agent that treats serious dermatologic conditions. It is a synthetic 13-cis isomer of naturally occurring tretinoin (trans-retinoic acid). Both agents are structurally related to vitamin A. It decreases sebaceous gland size and sebum production and may inhibit sebaceous gland differentiation and abnormal keratinization.
An FDA–mandated registry is now in place for all individuals prescribing, dispensing, or taking isotretinoin. For more information, see iPLEDGE. The registry aims to further decrease the risks of pregnancy and other unwanted and potentially dangerous adverse effects during a course of isotretinoin therapy.
Tretinoin topical (Retin-A)
Clinical Context:
Tretinoin topical inhibits microcomedo formation and eliminates the lesions present. It makes keratinocytes in sebaceous follicles less adherent and easier to remove. It is available as 0.025%, 0.05%, and 0.1% creams. It is also available as 0.01% and 0.025% gels.
Class Summary
Retinoids decrease the cohesiveness of abnormal hyperproliferative keratinocytes and may reduce the potential for malignant degeneration. They modulate keratinocyte differentiation and have been shown to reduce the risk of skin cancer formation in patients who have undergone renal transplantation.
Salicylic acid topical (Sal-Plant, Salactic film)
Clinical Context:
By dissolving the intercellular cement substance, salicylic acid produces desquamation of the horny layer of skin, while not affecting the structure of viable epidermis (concentrations of 12-17.6%). Consider the benefit-to-risk ratio in off-label use in Vohwinkel syndrome.
Urea (Ureaphil)
Clinical Context:
Urea promotes hydration and removal of excess keratin in conditions of hyperkeratosis. Use topical preparations of 10-30%.
Class Summary
Keratolytics cause cornified epithelium to swell, soften, macerate, and then desquamate.
Author
Zoltan Trizna, MD, PhD, Private Practice
Disclosure: Nothing to disclose.
Coauthor(s)
Dayna Diven, MD, Professor, Department of Dermatology, University of Texas Southwestern Austin Programs
Disclosure: Nothing to disclose.
Renée R Snyder, MD, Dermatologist, Private Practice
Disclosure: Nothing to disclose.
Specialty Editors
Michael J Wells, MD, FAAD, Dermatologic/Mohs Surgeon, The Surgery Center at Plano Dermatology
Disclosure: Nothing to disclose.
Chief Editor
Dirk M Elston, MD, Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine
Disclosure: Nothing to disclose.
Additional Contributors
Abby S Van Voorhees, MD, Assistant Professor, Director of Psoriasis Services and Phototherapy Units, Department of Dermatology, University of Pennsylvania School of Medicine, Hospital of the University of Pennsylvania
Disclosure: Received honoraria from Amgen for consulting; Received honoraria from Abbott for consulting; Partner received salary from Merck for management position; Received honoraria from Abbott for speaking and teaching; Received honoraria from Amgen for review panel membership; Received honoraria from Centocor for consulting; Received honoraria from Leo for consulting; Received none from Merck for other.
Acknowledgements
Mary Farley, MD Dermatologic Surgeon/Mohs Surgeon, Anne Arundel Surgery Center
Disclosure: Nothing to disclose.
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