Laboratory Studies

Molecular DNA analysis in pachyonychia congenita reveals missense mutations, deletion mutations, substitution mutations, and other mutations of keratin genes K6a, K6b, K16, and K17.

Oral leukokeratosis is to be differentiated from leukoplakia or cancer either by performing an oral biopsy or by recognizing its presence in patients with other symptoms of pachyonychia congenita.

Microscopy or culture of nail clippings or scrapings can help differentiate candidal or fungal onychomycosis from pachyonychia.

Histologic Findings

Histologic examination of plantar hyperkeratotic plaques reveals an acanthotic epidermis with parakeratosis and orthokeratosis compatible with rapid keratinocyte proliferation and differentiation. Cytologic atypia is not seen. Immunostaining shows positive immunostaining of K14, as would be expected along with K6, K16, K17 in the basal cell layer. In the suprabasal layers, K6, K16, K17, and K14 staining persists and K10 staining appears.^{[12, 19, 20]}

Electron microscopy on palmar or plantar plaques shows thickened and clumped intermediate filaments, as well as enlarged keratohyaline granules. In the broadened granular layer, thick masses of tonofilaments and large, irregular keratohyaline granules are present. In the spinous layer, thick masses of tonofilaments are found at the periphery of the cells.

Treatment & Management

Müller C. On the causes of congenital onychogryphosis. Mcn Med Wochenschr. 1904. 49:2180-2.
Wilson AG. Three cases of hereditary hyperkeratosis of the nail bed. Br J Dermatol. 1905. 17:13-14.
Jadassohn J, Lewandowsky F. Pachyonychia congenita. Keratosis disseminata circumscripta (follicularis). Tylomata. Leukokeratosis linguae. Jacob's Ikonographia Dermatologica. Berlin: Urban und Schwarzenberg; 1906. 1: 29-30.
McKusick V. Mendelian Inheritance in Man. 11th ed. Baltimore: J Hopkins University Press; 1994.
Eliason MJ, Leachman SA, Feng BJ, Schwartz ME, Hansen CD. A review of the clinical phenotype of 254 patients with genetically confirmed pachyonychia congenita. J Am Acad Dermatol. 2012 Jan 18. [QxMD MEDLINE Link].
Shah S, Boen M, Kenner-Bell B, Schwartz M, Rademaker A, Paller AS. Pachyonychia congenita in pediatric patients: natural history, features, and impact. JAMA Dermatol. 2014 Feb 1. 150(2):146-53. [QxMD MEDLINE Link].
Liao H, Sayers JM, Wilson NJ, Irvine AD, Mellerio JE, Baselga E. A spectrum of mutations in keratins K6a, K16 and K17 causing pachyonychia congenita. J Dermatol Sci. 2007 Dec. 48(3):199-205. [QxMD MEDLINE Link].
Terrinoni A, Smith FJ, Didona B, et al. Novel and recurrent mutations in the genes encoding keratins K6a, K16 and K17 in 13 cases of pachyonychia congenita. J Invest Dermatol. 2001 Dec. 117(6):1391-6. [QxMD MEDLINE Link].
Smith FJ, Liao H, Cassidy AJ, et al. The genetic basis of pachyonychia congenita. J Investig Dermatol Symp Proc. 2005 Oct. 10(1):21-30. [QxMD MEDLINE Link].
Kaspar RL. Challenges in developing therapies for rare diseases including pachyonychia congenita. J Investig Dermatol Symp Proc. 2005 Oct. 10(1):62-6. [QxMD MEDLINE Link].
Smith FJD, Kaspar RL, Schwartz ME, McLean WHI, Leachman SA. Pachyonychia Congenita. 1993. [QxMD MEDLINE Link].
Leachman SA, Kaspar RL, Fleckman P, et al. Clinical and pathological features of pachyonychia congenita. J Investig Dermatol Symp Proc. 2005 Oct. 10(1):3-17. [QxMD MEDLINE Link].
Wallis T, Poole CD, Hoggart B. Can skin disease cause neuropathic pain? A study in pachyonychia congenita. Clin Exp Dermatol. 2016 Jan. 41(1):26-33. [QxMD MEDLINE Link].
Brill S, Sprecher E, Smith FJD, Geva N, Gruener H, Nahman-Averbuch H, et al. Chronic pain in pachyonychia congenita: evidence for neuropathic origin. Br J Dermatol. 2018 Jul. 179 (1):154-162. [QxMD MEDLINE Link].
Feinstein A, Friedman J, Schewach-Millet M. Pachyonychia congenita. J Am Acad Dermatol. 1988 Oct. 19(4):705-11. [QxMD MEDLINE Link].
Munro CS. Pachyonychia congenita: mutations and clinical presentations. Br J Dermatol. 2001 May. 144(5):929-30. [QxMD MEDLINE Link].
Moon SE, Lee YS, Youn JI. Eruptive vellus hair cyst and steatocystoma multiplex in a patient with pachyonychia congenita. J Am Acad Dermatol. 1994 Feb. 30(2 Pt 1):275-6. [QxMD MEDLINE Link].
Clementi M, Cardin de Stefani E, Dei Rossi C, Avventi V, Tenconi R. Pachyonychia congenita Jackson-Lawler type: a distinct malformation syndrome. Br J Dermatol. 1986 Mar. 114(3):367-70. [QxMD MEDLINE Link].
Su WP, Chun SI, Hammond DE, Gordon H. Pachyonychia congenita: a clinical study of 12 cases and review of the literature. Pediatr Dermatol. 1990 Mar. 7(1):33-8. [QxMD MEDLINE Link].
Wollina U, Schaarschmidt H, Fünfstück V, Knopf B. Pachyonychia congenita. Immunohistologic findings. Zentralbl Pathol. 1991. 137(4):372-5. [QxMD MEDLINE Link].
Milstone LM, Fleckman P, Leachman SA, et al. Treatment of pachyonychia congenita. J Investig Dermatol Symp Proc. 2005 Oct. 10(1):18-20. [QxMD MEDLINE Link].
Tidman MJ, Wells RS. Control of plantar blisters in pachyonychia congenita with topical aluminium chloride. Br J Dermatol. 1988 Mar. 118(3):451-2. [QxMD MEDLINE Link].
Swartling C, Vahlquist A. Treatment of pachyonychia congenita with plantar injections of botulinum toxin. Br J Dermatol. 2006 Apr. 154(4):763-5. [QxMD MEDLINE Link].
González-Ramos J, Sendagorta-Cudós E, González-López G, Mayor-Ibarguren A, Feltes-Ochoa R, Herranz-Pinto P. Efficacy of botulinum toxin in pachyonychia congenita type 1: report of two new cases. Dermatol Ther. 2016 Jan. 29 (1):32-6. [QxMD MEDLINE Link].
Thomas DR, Jorizzo JL, Brysk MM, Tschen JA, Miller J, Tschen EH. Pachyonychia congenita. Electron microscopic and epidermal glycoprotein assessment before and during isotretinoin treatment. Arch Dermatol. 1984 Nov. 120(11):1475-9. [QxMD MEDLINE Link].
Dupre A, Christol B, Bonafe JL, Touron P. [Pachyonychia congenita. Three familial cases. Effects of the treatment by aromatic retinoid (RO 10.9359) (author's transl)]. Ann Dermatol Venereol. 1981. 108(2):145-9. [QxMD MEDLINE Link].
Hickerson RP, Leake D, Pho LN, Leachman SA, Kaspar RL. Rapamycin selectively inhibits expression of an inducible keratin (K6a) in human keratinocytes and improves symptoms in pachyonychia congenita patients. J Dermatol Sci. 2009 Nov. 56(2):82-8. [QxMD MEDLINE Link].
U.S. Food and Drug Administration (FDA). Orphan Drug Designations and Approvals. Sirolimus; treatment of pachyonychia congenita. Available at http://www.accessdata.fda.gov/scripts/opdlisting/oopd/OOPD_Results_2.cfm?Index_Number=391013. Accessed: January 24, 2014.
Teng JMC, Bartholomew FB, Patel V, Sun G. Novel treatment of painful plantar keratoderma in pachyonychia congenita using topical sirolimus. Clin Exp Dermatol. 2018 Dec. 43 (8):968-971. [QxMD MEDLINE Link].
Zhao Y, Gartner U, Smith FJ, McLean WH. Statins downregulate K6a promoter activity: a possible therapeutic avenue for pachyonychia congenita. J Invest Dermatol. 2011 May. 131 (5):1045-52. [QxMD MEDLINE Link].
Abdollahimajd F, Rajabi F, Shahidi-Dadras M, Saket S, Youssefian L, Vahidnezhad H, et al. Pachyonychia congenita: a case report of a successful treatment with rosuvastatin in a patient with a KRT6A mutation. Br J Dermatol. 2018 Oct 11. [QxMD MEDLINE Link].
Leachman SA, Hickerson RP, Schwartz ME, Bullough EE, Hutcherson SL, Boucher KM. First-in-human mutation-targeted siRNA phase Ib trial of an inherited skin disorder. Mol Ther. 2010 Feb. 18(2):442-6. [QxMD MEDLINE Link]. [Full Text].
Trochet D, Prudhon B, Vassilopoulos S, Bitoun M. Therapy for dominant inherited diseases by allele-specific RNA interference: successes and pitfalls. Curr Gene Ther. 2015. 15 (5):503-10. [QxMD MEDLINE Link].
Thomsen RJ, Zuehlke RL, Beckman BI. Pachyonychia congenita: surgical management of the nail changes. J Dermatol Surg Oncol. 1982 Jan. 8(1):24-8. [QxMD MEDLINE Link].
GARB J. Pachyonychia congenita; regression of plantar lesions on patients wearing specially made rubber base foot molds and shoes. Arch Derm Syphilol. 1950 Jul. 62(1):117-24. [QxMD MEDLINE Link].

Media Gallery

The most prominent feature is a substantially thickened, brownish gray nail plate with a rough surface.
Leukokeratosis of the oral mucosa is a prominent sign. Patchy whitish areas may be seen on the back of the tongue; the buccal mucosa; and sometimes, the gingiva.
Hyperkeratotic lesions of the skin may involve acanthosis, hyperkeratosis, and parakeratosis.

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Author

Saira J George, MD Assistant Professor, Department of Dermatology, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center

Saira J George, MD is a member of the following medical societies: American Academy of Dermatology, Houston Dermatological Society

Disclosure: Nothing to disclose.

Specialty Editor Board

David F Butler, MD Former Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Association of Military Dermatologists, Phi Beta Kappa, Texas Dermatological Society

Disclosure: Nothing to disclose.

Lester F Libow, MD Dermatopathologist, South Texas Dermatopathology Laboratory

Lester F Libow, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, Texas Medical Association

Disclosure: Nothing to disclose.

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: Received income in an amount equal to or greater than $250 from: Elsevier; WebMD<br/>Served as a speaker for various universities, dermatology societies, and dermatology departments.

Additional Contributors

Gregory J Raugi, MD, PhD Professor, Department of Internal Medicine, Division of Dermatology, University of Washington at Seattle School of Medicine; Chief, Dermatology Section, Primary and Specialty Care Service, Veterans Administration Medical Center of Seattle

Gregory J Raugi, MD, PhD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author, Aleksej Kansky, MD, PhD, to the development and writing of this article.

Pachyonychia Congenita Workup

Laboratory Studies

Histologic Findings

References

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