Granular Parakeratosis

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Granular Parakeratosis

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Granular parakeratosis, a benign condition, was first described in 1991 as a skin disease manifesting with erythematous hyperpigmented and hyperkeratotic papules and plaques of the cutaneous folds. [1] Granular parakeratosis is sometimes associated with pruritus. Granular parakeratosis has been associated with excessive use of topical preparations, in particular antiperspirants and deodorants; however, it has been found in persons who have not used such agents.

Granular parakeratosis is also associated with an occlusive environment, increased sweating, and, sometimes, local irritation. Some have linked it to obesity. New cases of granular parakeratosis continue to be reported involving different body regions. [2] Some suggest that granular parakeratosis has congenital links, [3] and others have considered if granular parakeratosis is a disease or a reactive process. [4] New cases are reported every year, and the disease is likely underdiagnosed. [5]

Note the image below.

The etiology of granular parakeratosis is uncertain, but Metze and Rütten [6] defended the hypothesis, first proposed by Northcutt et al, [1] that a basic defect exists in the processing of profilaggrin to filaggrin, which maintains the keratohyaline granules in the stratum corneum during cornification. Because granular parakeratosis has been associated with excessive use of topical preparations, an occlusive environment, increased sweating, and, sometimes, local irritation, some suggest that it is an allergic contact or irritant reaction. [7] Some patients who have manifested granular parakeratosis have not used topical preparations, and, thus, the causal linkage of granular parakeratosis to topical substances is unclear.

An interesting finding that mice that are deficient in caspase-14, an important protease necessary for the proper formation of a totally functional skin barrier, are more likely to develop parakeratosis may help elucidate the etiology of granular parakeratosis. [8]

In any case, the primary cause for granular parakeratosis remains unknown.

United States

Only approximately 40 case reports of granular parakeratosis have been published, but it is likely more common than the number of case reports suggests. Scheinfeld and Mones [9] reviewed the diagnoses of 363,343 specimens submitted to the Ackerman Institute of Dermatopathology in New York over a 5-year period. Eighteen (0.005%) of 363,343 specimens were diagnosed with granular parakeratosis. Scheinfeld and Mones [9] concluded that if the incidence of granular parakeratosis among biopsy specimens is representative of its general prevalence among persons with cutaneous eruptions, granular parakeratosis is rare.

The dermatopathology reports of the DermatoHistologisches Labor Dr. H. Laaff were reviewed for the diagnosis of granular parakeratosis. From 2004-2007, 10 cases (7 women, 3 men) of granular parakeratosis were noted, for a frequency of 0.004%. The average patient age was 62 years (range 33-82 y). In women, granular parakeratosis manifested in submammary areas (4), axillae (2), and popliteal fossa; in men, granular parakeratosis manifested in the groin (2) and genital areas. [10]

International

Only rare case reports of granular parakeratosis are noted, but it is probably not a rare condition. In 2002, Rodriguez [11] reported 3 cases of granular parakeratosis in women in Columbia.

No racial association has been reported for granular parakeratosis. Granular parakeratosis has been reported in blacks and whites.

Most reported cases of granular parakeratosis have occurred in women. Whether this finding represents a reporting bias or a real association is unclear.

The contention that white, middle-aged females are the primary group to experience granular parakeratosis was stressed in a 2013 article. [12]

Granular parakeratosis has been reported in children, [13, 14] but it is mostly reported in women aged 40-50 years. [15]

Northcutt AD, Nelson DM, Tschen JA. Axillary granular parakeratosis. J Am Acad Dermatol. 1991 Apr. 24(4):541-4. [Medline].

Niesmann J, Bierhoff E, Dirschka T. [Hyperkeratotic pruritic papules in the submammary area. Diagnose: Granular parakeratosis]. J Dtsch Dermatol Ges. 2010 Aug. 8(8):631-3. [Medline].

Leclerc-Mercier S, Prost-Squarcioni C, Hamel-Teillac D, Fraitag S. A case of congenital granular parakeratosis. Am J Dermatopathol. 2011 Jul. 33(5):531-3. [Medline].

Martorell A, Sanmartín O, Hueso-Gabriel L, Guillén C. [Granular parakeratosis: disease or reactive response?]. Actas Dermosifiliogr. 2011 Jan. 102(1):72-4. [Medline].

Channual J, Fife DJ, Wu JJ. Axillary granular parakeratosis. Cutis. 92(2):. 2013 Aug:61, 65-6. [Medline].

Metze D, Rutten A. Granular parakeratosis – a unique acquired disorder of keratinization. J Cutan Pathol. 1999 Aug. 26(7):339-52. [Medline].

Wallace CA, Pichardo RO, Yosipovitch G, Hancox J, Sangueza OP. Granular parakeratosis: a case report and literature review. J Cutan Pathol. 2003 May. 30(5):332-5. [Medline].

Hoste E, Denecker G, Gilbert B, Van Nieuwerburgh F, van der Fits L, Asselbergh B, et al. Caspase-14-Deficient Mice Are More Prone to the Development of Parakeratosis. J Invest Dermatol. 2013 Mar. 133(3):742-50. [Medline].

Scheinfeld NS, Mones J. Granular parakeratosis: pathologic and clinical correlation of 18 cases of granular parakeratosis. J Am Acad Dermatol. 2005 May. 52(5):863-7. [Medline].

Braun-Falco M, Laaff H. Granular parakeratosis–a clinical-pathological correlation of 10 cases. J Dtsch Dermatol Ges. 2009 Apr. 7(4):340-4. [Medline].

Rodriguez G. [Axillary granular parakeratosis]. Biomedica. 2002 Dec. 22(4):519-23. [Medline].

Brouwer MW, Kemperman PM. A female with axillary red-brown plaques. Br J Dermatol. 2013 Nov 9. [Medline].

Patrizi A, Neri I, Misciali C, Fanti PA. Granular parakeratosis: four paediatric cases. Br J Dermatol. 2002 Nov. 147(5):1003-6. [Medline].

Trowers AB, Assaf R, Jaworsky C. Granular parakeratosis in a child. Pediatr Dermatol. 2002 Mar-Apr. 19(2):146-7. [Medline].

Chang MW, Kaufmann JM, Orlow SJ, Cohen DE, Mobini N, Kamino H. Infantile granular parakeratosis: recognition of two clinical patterns. J Am Acad Dermatol. 2004 May. 50(5 Suppl):S93-6. [Medline].

Contreras ME, Gottfried LC, Bang RH, Palmer CH. Axillary intertriginous granular parakeratosis responsive to topical calcipotriene and ammonium lactate. Int J Dermatol. 2003 May. 42(5):382-3. [Medline].

Urbina F, Sudy E, Misad C. Two episodes of axillary granular parakeratosis triggered by different causes: case report. Acta Dermatovenerol Croat. 2012. 20(2):105-7. [Medline].

Pock L, Hercogova J. Incidental granular parakeratosis associated with dermatomyositis. Am J Dermatopathol. 2006 Apr. 28(2):147-9. [Medline].

Pock L, Cermakova A, Zipfelova J, Hercogova J. Incidental granular parakeratosis associated with molluscum contagiosum. Am J Dermatopathol. 2006 Feb. 28(1):45-7. [Medline].

Reddy IS, Swarnalata G, Mody T. Intertriginous granular parakeratosis persisting for 20 years. Indian J Dermatol Venereol Leprol. 2008 Jul-Aug. 74(4):405-7. [Medline].

Ezra N, Karunasiri D, Chiu MW. Unilateral pruritic axillary rash: axillary granular parakeratosis. Arch Dermatol. 2008 Dec. 144(12):1651. [Medline].

Akkaya AD, Oram Y, Aydın Ö. Infantile granular parakeratosis: cytologic examination of superficial scrapings as an aid to diagnosis. Pediatr Dermatol. 2015 May-Jun. 32 (3):392-6. [Medline].

Chan MP, Zimarowski MJ. Vulvar dermatoses: a histopathologic review and classification of 183 cases. J Cutan Pathol. 2015 Aug. 42 (8):510-8. [Medline].

Paradisi A, Sisto T, Annessi G. Groin granular parakeratosis. Eur J Dermatol. 2010 Mar-Apr. 20(2):242-3. [Medline].

Niesmann J, Bierhoff E, Dirschka T. [Hyperkeratotic pruritic papules in the submammary area. Diagnose: Granular parakeratosis]. J Dtsch Dermatol Ges. 2010 Aug 1. 8(8):631-3. [Medline].

Resnik KS, Kantor GR, DiLeonardo M. Granular parakeratotic acanthoma. Am J Dermatopathol. 2005 Oct. 27(5):393-6. [Medline].

Joshi R, Taneja A. Granular parakeratosis presenting with facial keratotic papules. Indian J Dermatol Venereol Leprol. 2008 Jan-Feb. 74(1):53-5. [Medline].

Genebriera J, Davis MD, Yang H, Borrowman TA. Papillomatous axillary rash due to granular parakeratosis. J Eur Acad Dermatol Venereol. 2007 Aug. 21(7):994-5. [Medline].

Brouwer MW, Kemperman PM. A woman with axillary red-brown plaques. Br J Dermatol. 2014 Feb. 170(2):479-80. [Medline].

Mehregan DA, Vandersteen P, Sikorski L, Mehregan DR. Axillary granular parakeratosis. J Am Acad Dermatol. 1995 Aug. 33(2 Pt 2):373-5. [Medline].

Resnik KS, DiLeonardo M. Follicular granular parakeratosis. Am J Dermatopathol. 2003 Oct. 25(5):428-9. [Medline].

Resnik KS, Kantor GR, DiLeonardo M. Dermatophyte-related granular parakeratosis. Am J Dermatopathol. 2004 Feb. 26(1):70-1. [Medline].

Resnik KS, DiLeonardo M. Incidental granular parakeratotic cornification in carcinomas. Am J Dermatopathol. 2007 Jun. 29(3):264-9. [Medline].

Yang JH, Lee HM, Noh TK, Won CH, Chang S, Lee MW, et al. Granular parakeratosis of eccrine ostia. Ann Dermatol. 2012 May. 24:203-5. [Medline].

Brown SK, Heilman ER. Granular parakeratosis: resolution with topical tretinoin. J Am Acad Dermatol. 2002 Nov. 47(5 Suppl):S279-80. [Medline].

Compton AK, Jackson JM. Isotretinoin as a treatment for axillary granular parakeratosis. Cutis. 2007 Jul. 80(1):55-6. [Medline].

Webster CG, Resnik KS, Webster GF. Axillary granular parakeratosis: response to isotretinoin. J Am Acad Dermatol. 1997 Nov. 37(5 Pt 1):789-90. [Medline].

Ravitskiy L, Heymann WR. Botulinum toxin-induced resolution of axillary granular parakeratosis. Skinmed. 2005 Mar-Apr. 4(2):118-20. [Medline].

Samrao A, Reis M, Niedt G, Rudikoff D. Granular parakeratosis: response to calcipotriene and brief review of current therapeutic options. Skinmed. 2010 Nov-Dec. 8(6):357-9. [Medline].

Patel U, Patel T, Skinner RB Jr. Resolution of granular parakeratosis with topical calcitriol. Arch Dermatol. 2011 Aug. 147:997-8. [Medline].

Ozkanli S, Zemheri E, Karadag AS, Akbulak O, Zenginkinet T, Zindanci I, et al. A comparative study of histopathological findings in skin biopsies from patients with psoriasis before and after treatment with acitretin, methotrexate and phototherapy. Cutan Ocul Toxicol. 2014 Sep 29. 1-6. [Medline].

Noah S Scheinfeld, JD, MD, FAAD Assistant Clinical Professor, Department of Dermatology, Weil Cornell Medical College; Consulting Staff, Department of Dermatology, St Luke’s Roosevelt Hospital Center, Beth Israel Medical Center, New York Eye and Ear Infirmary; Assistant Attending Dermatologist, New York Presbyterian Hospital; Assistant Attending Dermatologist, Lenox Hill Hospital, North Shore-LIJ Health System; Private Practice

Noah S Scheinfeld, JD, MD, FAAD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

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.

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

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

Disclosure: Nothing to disclose.

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