Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Acrokeratosis Verruciformis of Hopf Clinical Presentation

  • Author: Sarah Sweeney Pinney, MD; Chief Editor: William D James, MD  more...
 
Updated: Apr 14, 2016
 

History

Acrokeratosis verruciformis is usually present at birth or manifests in early childhood, but the onset may be delayed until the fifth decade of life. Acrokeratosis verruciformis of Hopf has an autosomal dominant mode of transmission, but sporadic cases also occur.[15, 16]

Next

Physical

Dry, rough, skin-colored or reddish-brown, flat-topped, or warty papules resembling flat warts are observed, particularly on the dorsum of the hands and, at times, on the dorsum of the feet, as shown in the image below.

Papules also may be found on the knees, elbows, forearms, or lower legs. Small groups or isolated papules may develop on other parts of the body. Papules sometimes are more easily felt than seen.

Palmar skin may be thickened and may show punctate keratosis, pits, or punctiform breaks in dermatoglyphics, identical to those observed in persons with Darier disease or Grover disease.[17]

Nail involvement, including longitudinal splitting, striations, and subungual hyperkeratosis, also may be seen.[18]

Variants can also present on the trunk, as is seen in a case following the lines of Blaschko.[19]

This photos shows flat-topped, hyperkeratotic, ski This photos shows flat-topped, hyperkeratotic, skin colored papules on the dorsal hands without palmar involvement. This patient also has dystrophy of the fingernails, which is not easily visible in this photograph. Biopsy demonstrated epidermal acanthosis and papillomatosis with hyperkeratosis. Photo courtesy of Sarah S. Pinney, MD.
Previous
Next

Causes

Acrokeratosis verruciformis of Hopf has an autosomal dominant mode of transmission. This has been suggested since 1962, in a large follow-up series by Niedleman and McKusick that described 24 cases in 4 generations in the same family.[2]

Sporadic cases can also occur.[15]

Acrokeratosis verruciformis and Darier disease are allelic disorders. ATP2A2 encoding the SERCA2 pump has been identified as the defective gene in Darier disease. In 2003, Dhitavat et al identified a heterozygous P602L mutation in the ATP2A2 gene in a family affected with acrokeratosis verruciformis for 6 generations.[11] This mutation predicts a nonconservative amino acid substitution in the ATP-binding domain of the molecule. The mutation segregates with the disease phenotype in the family and was not found in 50 controls. Moreover, functional analysis of the P602L mutant showed that it has lost its ability to transport Ca2+. This result demonstrates loss of function of the SERCA2 mutant in acrokeratosis verruciformis, thus providing evidence that acrokeratosis verruciformis and Darier disease are allelic disorders.

Exceptionally, a similar association with Hailey-Hailey disease has been reported.[20]

Acrokeratosis verruciformis of Hopf has been reported in a patient with nevoid basal cell carcinoma syndrome.[21]

The possible occurrence of squamous cell carcinoma in the context of the lesions of acrokeratosis verruciformis of Hopf has been rarely described, and one case report describes an association with keratoacanthomas.[22, 23]

This condition may also be associated with hypertrophic lichen planus and multiple steatocystomas.[24]

Previous
 
 
Contributor Information and Disclosures
Author

Sarah Sweeney Pinney, MD Assistant Professor, Department of Dermatology, University of Texas Medical School at Houston

Sarah Sweeney Pinney, MD is a member of the following medical societies: American Academy of Dermatology, Texas Dermatological Society, Texas Medical Association, Women's Dermatologic Society

Disclosure: Nothing to disclose.

Coauthor(s)

Ronald P Rapini, MD Professor and Chair, Department of Dermatology, The University of Texas MD Anderson Cancer Center; Distinguished Chernosky Professor and Chair of Dermatology, Professor of Pathology, University of Texas McGovern Medical School at Houston

Ronald P Rapini, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Society for Investigative Dermatology, Texas Medical Association

Disclosure: Received royalty from Elsevier publishers for independent contractor; May receive consulting fee from FDA panel for consulting in future, since I am on one of their committees, but at this time so far have received zero from FDA.

Rashid M Rashid, MD, PhD Director, Mosaic Clinic Hair Transplant Center of Houston

Rashid M Rashid, MD, PhD is a member of the following medical societies: American Academy of Dermatology, Texas Medical Association, Texas Dermatological Society, International Society of Hair Restoration Surgery, Council for Nail Disorders, Houston Dermatological Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Steven R Feldman, MD, PhD Professor, Departments of Dermatology, Pathology and Public Health Sciences, and Molecular Medicine and Translational Science, Wake Forest Baptist Health; Director, Center for Dermatology Research, Director of Industry Relations, Department of Dermatology, Wake Forest University School of Medicine

Steven R Feldman, MD, PhD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, North Carolina Medical Society, Society for Investigative Dermatology

Disclosure: Received honoraria from Amgen for consulting; Received honoraria from Abbvie for consulting; Received honoraria from Galderma for speaking and teaching; Received consulting fee from Lilly for consulting; Received ownership interest from www.DrScore.com for management position; Received ownership interest from Causa Reseasrch for management position; Received grant/research funds from Janssen for consulting; Received honoraria from Pfizer for speaking and teaching; Received consulting fee from No.

Chief Editor

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Arash Taheri, MD Research Fellow, Center for Dermatology Research, Department of Dermatology, Wake Forest University School of Medicine

Disclosure: Nothing to disclose.

Acknowledgements

Mohsin Ali, MBBS, FRCP, MRCP, MRCPI Consulting Staff, Department of Dermatology, Amersham General Hospital, UK

Disclosure: Nothing to disclose.

Doina Ivan, MD Assistant Professor of Pathology, Assistant Professor, Department of Dermatology, Division of Pathology/Lab Medicine, The University of Texas MD Anderson Cancer Center

Doina Ivan, MD is a member of the following medical societies: American Society for Clinical Pathology, American Society of Dermatopathology, College of American Pathologists, International Society of Dermatopathology, and United States and Canadian Academy of Pathology

Disclosure: Nothing to disclose.

References
  1. Hopf G. Ueber eine bisher nicht beschriebene disseminierte keratose (akrokeratose verruciformis). Dermatol Z. 1931. 60:227-50.

  2. Niedleman ML, Mckusick VA. Acrokeratosis verruciformis (Hopf). A follow-up study. Arch Dermatol. 1962 Dec. 86:779-82. [Medline].

  3. Bang CH, Kim HS, Park YM, Kim HO, Lee JY. Non-familial Acrokeratosis Verruciformis of Hopf. Ann Dermatol. 2011 Sep. 23 Suppl 1:S61-3. [Medline]. [Full Text].

  4. Panja RK. Acrokeratosis verruciformis: (Hopf)--A clinical entity?. Br J Dermatol. 1977 Jun. 96(6):643-52. [Medline].

  5. Waisman M. Verruciform manifestations of keratosis follicularis. Arch Dermatol. 1960. 81:1-14.

  6. Bergman R, Sezin T, Indelman M, Helou WA, Avitan-Hersh E. Acrokeratosis verruciformis of Hopf showing P602L mutation in ATP2A2 and overlapping histopathological features with Darier disease. Am J Dermatopathol. 2012 Aug. 34(6):597-601. [Medline].

  7. Robertson L, Sauder MB. Basal Cell Carcinoma in Type 2 Segmental Darier's Disease. J Skin Cancer. 2012. 2012:839561. [Medline]. [Full Text].

  8. Wang Y, Bruce AT, Tu C, Ma K, Zeng L, Zheng P, et al. Protein aggregation of SERCA2 mutants associated with Darier disease elicits ER stress and apoptosis in keratinocytes. J Cell Sci. 2011 Nov 1. 124:3568-80. [Medline]. [Full Text].

  9. Sakuntabhai A, Ruiz-Perez V, Carter S, Jacobsen N, Burge S, Monk S. Mutations in ATP2A2, encoding a Ca2+ pump, cause Darier disease. Nat Genet. 1999 Mar. 21(3):271-7. [Medline].

  10. Bergman R, Sezin T, Indelman M, Helou WA, Avitan-Hersh E. Acrokeratosis verruciformis of Hopf showing P602L mutation in ATP2A2 and overlapping histopathological features with Darier disease. Am J Dermatopathol. 2012 Aug. 34 (6):597-601. [Medline].

  11. Dhitavat J, Macfarlane S, Dode L, et al. Acrokeratosis verruciformis of Hopf is caused by mutation in ATP2A2: evidence that it is allelic to Darier's disease. J Invest Dermatol. 2003 Feb. 120(2):229-32. [Medline].

  12. Liang YH, Zhang QG, Liu QX. Two novel missense mutations of ATP2A2 in two Chinese patients with sporadic Darier Disease. Clin Exp Dermatol. 2014 Oct 4. [Medline].

  13. Wang PG, Gao M, Lin GS, Yang S, Lin D, Liang YH. Genetic heterogeneity in acrokeratosis verruciformis of Hopf. Clin Exp Dermatol. 2006 Jul. 31(4):558-63. [Medline].

  14. Shi BJ, Xue M, Zhu YJ, Wang SP, Du Y, Chen DY, et al. Exon 12 of the ATP2A2 gene in patients with Darier disease: one novel mutation and one previously described. J Eur Acad Dermatol Venereol. 2014 Feb 19. [Medline].

  15. Schueller WA. Acrokeratosis verruciformis of Hopf. Arch Dermatol. 1972 Jul. 106(1):81-3. [Medline].

  16. Bang CH, Kim HS, Park YM, Kim HO, Lee JY. Non-familial Acrokeratosis Verruciformis of Hopf. Ann Dermatol. 2011 Sep. 23 Suppl 1:S61-3. [Medline].

  17. Raff M, Szilvassy J. Specific dermatoglyphic patterns: a characteristic manifestation of acantholytic dyskeratotic dermatoses. J Am Acad Dermatol. 1989 Nov. 21(5 Pt 1):958-60. [Medline].

  18. Herndon J, Wilson J. Acrokeratosis (Hopf) and Darier's disease. Arch Dermatol. 1966. 93:305-10.

  19. Nair PA. Acrokeratosis verruciformis of hopf along lines of blaschko. Indian J Dermatol. 2013 Sep. 58(5):406. [Medline].

  20. Yakis G, Csato M, Kemeny L, Korom I, Morvay M, Dobozy A. Hailey-Hailey disease with acrokeratosis verruciformis Hopf. Acta Derm Venereol. 1996 Mar. 76(2):157. [Medline].

  21. Humbert P, Laurent R, Faivre B, Agache P. Nevoid basal cell carcinoma syndrome and acrokeratosis verruciformis. Occurrence of two rare inherited autosomal dominant conditions in the same patient. Dermatologica. 1990. 180(3):169-70. [Medline].

  22. Dogliotti M, Schmaman A. Acrokeratosis verruciformis: malignant transformation. Dermatologica. 1971. 143(2):95-9. [Medline].

  23. Farro P, Zalaudek I, Ferrara G, et al. Unusual association between acrokeratosis verruciformis of Hopf and multiple keratoacanthomas. Successful therapy with acitretin. J Dtsch Dermatol Ges. 2004 Jun. 2(6):440-2. [Medline].

  24. Verbov J. Acrokeratosis verruciformis of Hopf with steatocystoma multiplex and hypertrophic lichen planus. Br J Dermatol. 1972 Jan. 86(1):91-4. [Medline].

  25. Su WP. Histopathologic varieties of epidermal nevus. A study of 160 cases. Am J Dermatopathol. 1982 Apr. 4(2):161-70. [Medline].

  26. Murayama S, Mizawa M, Takegami Y, Makino T, Shimizu T. Two cases of keratosis follicularis squamosa (Dohi) caused by swimsuit friction. Eur J Dermatol. 2013 Apr 1. 23(2):230-2. [Medline].

  27. Cosulich MT, Norton SA. Dermatographic fixed-drug eruption: another cause of pseudo-Darier's sign. Skinmed. 2013 Nov-Dec. 11(6):368-9. [Medline].

  28. Serarslan G, Balci DD, Homan S. Acitretin treatment in acrokeratosis verruciformis of Hopf. J Dermatolog Treat. 2007. 18(2):123-5. [Medline].

  29. Serarslan G, Balci DD, Homan S. Acitretin treatment in acrokeratosis verruciformis of Hopf. J Dermatolog Treat. 2007. 18 (2):123-5. [Medline].

 
Previous
Next
 
This photos shows flat-topped, hyperkeratotic, skin colored papules on the dorsal hands without palmar involvement. This patient also has dystrophy of the fingernails, which is not easily visible in this photograph. Biopsy demonstrated epidermal acanthosis and papillomatosis with hyperkeratosis. Photo courtesy of Sarah S. Pinney, MD.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.