You are in: eMedicine Specialties > Dermatology > PAPULOSQUAMOUS DISEASES Vohwinkel SyndromeArticle Last Updated: Feb 28, 2007AUTHOR AND EDITOR INFORMATIONSection 1 of 11
  Author: Zoltan Trizna, MD, PhD, Private Practice Zoltan Trizna is a member of the following medical societies: American Academy of Dermatology, American Medical Association, and Texas Medical Association Coauthor(s): Renée R Snyder, MD, Dermatologist, Private Practice; Dayna Diven, MD, Clinical Professor, Department of Dermatology, University of Texas Medical Branch at Galveston Editors: 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; Michael J Wells, MD, Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center; Mary Farley, MD, Dermatologic Surgeon/Mohs Surgeon, Anne Arundel Surgery Center; Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania; Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center Author and Editor Disclosure Synonyms and related keywords: keratoderma hereditaria mutilans, palmoplantar keratoderma mutilans, autoamputation, palmar keratosis, plantar keratosis, pseudo-ainhum, hearing loss INTRODUCTIONSection 2 of 11
  BackgroundIn 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. Pseudo-ainhum 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.
PathophysiologyVohwinkel syndrome belongs to the group of palmoplantar keratodermas. It is considered to have an autosomal dominant inheritance, although sporadic cases have also been described. 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. 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. The other 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. FrequencyInternationalThe syndrome is rare, with fewer than 30 cases reported. Mortality/MorbidityPatients 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. RaceNo racial predominance is noted. SexNo sex predominance is reported. AgeThis syndrome usually manifests between infancy and early childhood. CLINICALSection 3 of 11
History
Physical
Causes
DIFFERENTIALSSection 4 of 11
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| Drug Name | Isotretinoin (Accutane) |
|---|---|
| Description | PO agent that treats serious dermatologic conditions. Synthetic 13-cis isomer of naturally occurring tretinoin (trans-retinoic acid). Both agents are structurally related to vitamin A. Decreases sebaceous gland size and sebum production. May inhibit sebaceous gland differentiation and abnormal keratinization. |
| Adult Dose | 0.6 mg/kg/d PO |
| Pediatric Dose | Not recommended |
| Contraindications | Documented hypersensitivity; breastfeeding; psychiatric disorders, especially depression and/or suicidal tendencies |
| Interactions | Toxicity may occur with vitamin A coadministration; pseudotumor cerebri or papilledema may occur when coadministered with tetracyclines; may reduce plasma levels of carbamazepine Increases toxicity of methotrexate (avoid concomitant use); interferes with effects of microdose progestin minipill; coadministration with alcohol may result in formation of etretinate, which has much longer half-life than acitretin (>120 d); may increase toxicity of phenytoin |
| Pregnancy | X - Contraindicated in pregnancy |
| Precautions | May decrease night vision; inflammatory bowel disease may occur; may be associated with development of hepatitis and pancreatitis; diabetes patients may experience problems in controlling blood glucose while on isotretinoin; avoid exposure to UV light or sunlight until tolerance achieved; discontinue treatment if rectal bleeding, abdominal pain, or severe diarrhea occurs; mood swings or depression may occur; caution in history of depression |
| Drug Name | Tretinoin (Retin-A) |
|---|---|
| Description | Inhibits microcomedo formation and eliminates lesions present. Makes keratinocytes in sebaceous follicles less adherent and easier to remove. Available as 0.025%, 0.05%, and 0.1% creams. Available also as 0.01% and 0.025% gels. |
| Adult Dose | Begin with lowest tretinoin formulation and increase as tolerated; apply hs or qod; lower frequency of application if irritation develops |
| Pediatric Dose | <12 years: Not established >12 years: Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | Toxicity increases with coadministration of benzoyl peroxide, salicylic acid, and resorcinol; avoid topical sulfur, resorcinol, salicylic acid, other keratolytics, abrasives, astringents, spices, and lime |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Photosensitivity may occur with excessive sunlight exposure; caution in eczema; do not apply to mucous membranes, mouth, and angles of nose |
Cause cornified epithelium to swell, soften, macerate, and then desquamate.
| Drug Name | Salicylic acid (Sal-Plant, Salactic film) |
|---|---|
| Description | 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 benefit-to-risk ratio in off-label use in Vohwinkel syndrome. |
| Adult Dose | Apply topically qd/bid |
| Pediatric Dose | Apply as in adults |
| Contraindications | Documented hypersensitivity; prolonged use in infants, patients with diabetes mellitus, and those with impaired circulation; use on moles, birthmarks or warts with hair growing from them, genital or facial warts, warts on mucous membranes, irritated skin, or any area infected or reddened |
| Interactions | None reported |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Avoid contact with mucous membranes, normal skin surrounding warts, and eyes; immediately flush with water for 15 min if contact with eyes or mucous membranes occurs; avoid inhaling vapors |
| Drug Name | Urea (Ureaphil) |
|---|---|
| Description | Promotes hydration and removal of excess keratin in conditions of hyperkeratosis. Use topical preparations of 10-30%. |
| Adult Dose | Apply qd/bid to affected areas |
| Pediatric Dose | Apply as in adults |
| Contraindications | Documented hypersensitivity; severely impaired renal function; active intracranial bleeding; marked dehydration; frank liver failure; infusion into veins of lower extremities in elderly patients (may cause phlebitis and thrombosis) |
| Interactions | May decrease effects of lithium |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Do not use if intracranial bleeding is present, unless prior to surgical intervention to control hemorrhage has been performed (reduction of brain edema by urea may result in reactivation of intracranial bleeding); may increase risk of venous thrombosis and hemoglobinuria in hypothermic patients; caution in renal impairment |
| Media file 1: Starfish-shaped plaques. | |
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| Media file 2: Palmar hyperkeratosis. | |
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| Media file 3: Pseudo-ainhum. | |
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Article Last Updated: Feb 28, 2007
