eMedicine Specialties > Dermatology > Papulosquamous Diseases

Granular Parakeratosis

Noah S Scheinfeld, MD, JD, FAAD, Assistant Clinical Professor, Department of Dermatology, Columbia University; Consulting Staff, Department of Dermatology, New York Medical College-Metropolitan Hospital; Private Practice

Updated: Jan 29, 2008

Introduction

Background

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 It 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. It is also associated with an occlusive environment, increased sweating, and, sometimes, local irritation. Some have linked it to obesity.

Pathophysiology

The etiology of granular parakeratosis is uncertain, but Metze and R ü tten² 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.³ 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. The primary cause for this disease remains unknown.

See Contact Dermatitis, Allergic and Contact Dermatitis, Irritant for more information on those topics.

Frequency

United States

Only approximately 40 case reports of this condition have been published, but it is likely more common than the number of case reports suggests. Scheinfeld and Mones⁴ 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 Mones⁴ concluded that if the incidence of granular parakeratosis among biopsy specimens is representative of its general prevalence among persons with cutaneous eruptions, the condition is rare.

International

Only rare case reports are noted, but it is probably not a rare condition. In 2002, Rodriguez⁵ reported 3 cases in women in Columbia.

Mortality/Morbidity

Its only associated symptom is pruritus.

Race

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

Sex

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

Age

Granular parakeratosis has been reported in children,^6,7 but it is mostly reported in women aged 40-50 years.⁸

Clinical

History

Patients present with a 1- to 12-month history of axillary or intertriginous rash. Sometimes, the rash is pruritic; sometimes, it is not.

• In 2005, Scheinfeld and Mones⁴ demonstrated that granular parakeratosis usually occurs in women in their axillae.
• Patients may report a history of applying antiperspirants and deodorants in the immediate period before the rash started. In 2003, Contreras et al⁹ noted that a 70-year-old man reported a burning sensation in the area of granular parakeratosis.
• In another report, mothers reported changing their granular parakeratosis infants' diapers 5-7 times daily. The mothers reported thoroughly washing the area with liquid soap after every diaper change. The mothers also always applied zinc oxide powders and/or pastes to the affected areas.⁶
• In 2002, Rodriguez⁵ reported 3 cases in obese women.
• A number of incidental incidences of granular parakeratosis have been reported, including associations with dermatomyositis¹⁰  and molluscum contagiosum.¹¹ The case of molluscum contagiosum involved a woman with trunk and extremity involvement after a 4-month history of a slowly progressive pruritic papular eruption.

Physical

Granular parakeratosis manifests with intertriginous (ie, groin, intermammary or submammary region, and abdominal folds) bilateral or unilateral brown- or red-crusted patches, papules, or plaques. The rash can be confluent or reticulated. Even when patches or plaques are present, discrete papules can also be present. Granular parakeratosis can appear as slightly erythematous and lichenified plaques.

• In children, granular parakeratosis has been reported to occur in the groin, on the lower back, on the buttocks, and on the flanks.
• Granular parakeratosis reportedly can occur as a solitary keratosis, which is termed granular parakeratotic acanthoma. This appears to be in the same family as acantholytic dyskeratotic acanthoma and epidermolytic acanthoma.¹²
• Granular parakeratosis manifesting as facial keratotic papules has been reported.¹³
• Genebriera et al¹⁴ noted a papillomatous axillary rash due to granular parakeratosis.

Causes

The cause of granular parakeratosis is uncertain. Although controversial, the following have been implicated as etiologies for granular parakeratosis:

• Use of topical solutions or creams, in particular antiperspirants and deodorants¹⁵
• Presence of an occlusive environment
• Increased sweating
• Local irritants

Importantly, because cases have been reported when these factors were not been present, their importance is not clear.

In children, excessive washing has been noted in a series of 4 patients.⁶

Several authors have postulated that in granular parakeratosis, a basic defect exists in the processing of profilaggrin to filaggrin. Filaggrin maintains the keratohyaline granules in the stratum corneum during cornification.

Differential Diagnoses

Acanthosis Nigricans
Bowen Disease
Confluent and Reticulated Papillomatosis
Erythrasma
Extramammary Paget Disease

Other Problems to Be Considered

Inverse psoriasis
Inverse lichen planus
Inverse pityriasis rosea
Pemphigus vegetans
Benign familial pemphigus

Workup

Laboratory Studies

A potassium hydroxide preparation can be used to check for fungus.

Other Tests

A Wood lamp can be used to check for erythrasma.

Procedures

A skin biopsy is the most useful test in establishing the diagnosis of granular parakeratosis.

Histologic Findings

Characteristic histologic findings include psoriasiform hyperplasia, a thickened stratum corneum with retention of keratohyalin granules, and parakeratosis.¹⁵ Most investigators report a well-developed granular layer and a sparse lymphohistiocytic inflammatory infiltrate. The retained granular layer sometimes demonstrates focal vacuolization.

• In 2003, Resnik and DiLeonardo¹⁶ described a follicular granular parakeratosis that was a granular parakeratosis confined to the follicle.
• In 2004, Resnik et al¹⁷ described dermatophyte-related granular parakeratosis.
• Incidental granular parakeratosis has been associated with carcinomas,¹⁸ dermatomyositis,¹⁰ and molluscum contagiosum.¹¹
• Resnik et al¹² have noted the existence of a granular parakeratotic acanthoma.

Treatment

Medical Care

Although some consider the condition rare, successful medical treatments for granular parakeratosis have been reported. These have included topical corticosteroids and oral and topical retinoids.^19,20 A 2003 report notes that topical calcipotriene and ammonium lactate also effectively treated this condition.⁹ Calcineurin inhibitors and topical antifungal agents have been tried with some success. Isotretinoin^20,21 and tretinoin¹⁹ have been reported as effective for the condition, as has botulinum toxin injection.²²

Surgical Care

Rare reports have noted that cryotherapy can effectively treat granular parakeratosis.

Activity

Patients should avoid excessive washing of intertriginous areas. They should also minimize or avoid the use of roll-on deodorants and antiperspirants.

Medication

The goals of pharmacotherapy are to reduce pruritus and to improve the appearance of the eruption that manifests with granular parakeratosis.

Retinoids

These agents are vitamin A analogues involved in modulation of cell growth, division, reproduction, and differentiation. Their biologic effects result from alterations in gene expressions that are mediated through 2 major types of nuclear receptors: the retinoic acid receptor and the retinoic X receptor. Each receptor subtype likely controls the expression of both unique genes and common genes. Subclass-specific retinoids are available. Systemic retinoids very likely are not indicated for this harmless condition, but they could perhaps be used in exceptional cases.

The article " Clinical Review: Topical Retinoids " may also be helpful.

Isotretinoin (Accutane)

Oral agent that treats serious dermatologic conditions. Isotretinoin is the synthetic 13-cis isomer of the naturally occurring tretinoin (trans- retinoic acid). Both agents are structurally related to vitamin A. Isotretinoin is a second-line treatment because it has frequent adverse effects and because topical medications can effectively treat this condition.

Dosing

Adult

Some have suggested a dose of 0.5-1 mg/kg/d PO until the condition resolves, but, if used, dose should not exceed 20 mg/d

Pediatric

Not recommended

Interactions

Toxicity may occur with vitamin A coadministration; pseudotumor cerebri or papilledema may occur when coadministered with tetracyclines; may reduce carbamazepine plasma levels

Contraindications

Documented hypersensitivity; pregnancy

Precautions

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

May decrease night vision; inflammatory bowel disease may occur; may be associated with development of hepatitis; occasional exaggerated healing response of acne lesions (excessive granulation with crusting) may occur; patients with diabetes may experience problems in controlling blood glucose levels while on isotretinoin; avoid exposure to UV light or sunlight until tolerance achieved; discontinue treatment if rectal bleeding, abdominal pain, or severe diarrhea occur; mood swings or depression may occur; caution if history of depression

Tretinoin (Avita, Retin-A, Renova)

Inhibits microcomedo formation and eliminates existing lesions. Makes keratinocytes in sebaceous follicles less adherent and easier to remove. Available as 0.025%, 0.05%, and 0.1% creams. Also available as 0.01% and 0.025% gels. Can be a first-line treatment in granular parakeratosis but is irritating and should be used with caution.

Dosing

Adult

Apply topically qd

Pediatric

Not established

Interactions

Other skin irritants (eg, astringents, benzoyl peroxide, salicylic acid, resorcinol, topical sulfur, other keratolytics, abrasives, spices, lime) may exacerbate irritation; coadministration with other drugs causing photosensitivity (eg, tetracycline, sulfonamides) may increase risk of sunburn

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Photosensitivity may occur with excessive sunlight exposure; burning, stinging, peeling, pruritus, or erythema has been reported at site of application; caution with eczema (may cause severe irritation); do not apply to mucous membranes, mouth, and angles of nose

Tazarotene (Tazorac)

Topical medication approved for psoriasis and acne. Useful in normalizing functioning of epithelial cells. Acts on a genetic level, leading to the transcription of certain retinoic acid genes. Use is off-label.

Dosing

Adult

Apply to rash qd

Pediatric

Apply as in adults

Interactions

Do not use concomitantly with dermatologic drugs or cosmetics that have a strong drying effect on skin (eg, salicylic acid, benzoyl peroxide, astringents)

Contraindications

Documented hypersensitivity; excess irritation; pregnancy

Precautions

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

May cause burning or stinging sensations; discontinue if excessive irritation occurs; rinse thoroughly if contact with eyes, eyelids, or mouth; may cause severe irritation in eczematous skin; photosensitivity may occur

Vitamins

These agents are essential for normal DNA synthesis and metabolism of proteins, carbohydrates, and fats. They may also work as cofactors used in aerobic cellular respiration.

Calcipotriene (Dovonex)

Topical preparation containing vitamin D-3. Indicated for psoriasis. Seems to normalize maturation of epidermal cells.

Dosing

Adult

Apply to rash bid

Pediatric

Apply as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity; hypercalcemia; vitamin D toxicity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Rarely can lead to elevated serum calcium level; discontinue treatment if skin becomes irritated; discontinue if serum calcium level is increased outside reference range

Moisturizers

This agent normalizes skin function.

Lactic acid (Lac Hydrin, AmLactin)

Topical medication used to treat dry skin. Relieves itching and aids in healing skin in mild eczemas and dermatoses, itching skin, minor wounds, and minor skin irritations. Found in a variety of topical emollient lotions.

Dosing

Adult

Apply 1-3 times/d

Pediatric

Apply as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May cause stinging and burning at the site of application

Corticosteroids

These agents have both anti-inflammatory (glucocorticoid) properties and salt-retaining (mineralocorticoid) properties. Glucocorticoids have profound and varied metabolic effects. In addition, these agents modify the body's immune response to diverse stimuli.

Hydrocortisone (CortaGel, Cortaid, Dermacort)

Adrenocorticosteroid derivative suitable for application to skin or external mucous membranes. Decreases inflammation by suppression of migration of polymorphonuclear leukocytes and reversal of increased capillary permeability. Can be a first-line treatment in this condition but can cause striae and skin thinning when used in axillary or groin areas.

Dosing

Adult

Apply qd/bid

Pediatric

Not established

Interactions

None reported

Contraindications

Documented hypersensitivity; viral, fungal, and bacterial skin infections

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Prolonged use, applying over large surface areas, applying potent steroids, and using occlusive dressings may increase systemic absorption of corticosteroids and may cause Cushing syndrome, reversible HPA-axis suppression, hyperglycemia, and glycosuria; use with caution in axillary and groin areas (can cause striae and skin thinning)

Follow-up

Deterrence/Prevention

Once the condition resolves and the inciting substances are avoided, granular parakeratosis does not tend to recur. However, sometimes, it has a chronic and relapsing course. Patients should not use occlusive compounds and should avoid excessive washing of axillary areas, groin, or other affected areas.

Prognosis

The prognosis is good with any form of treatment and avoidance of the inciting factors. However, sometimes, granular parakeratosis resists treatment and has a chronic and relapsing course.

Miscellaneous

Medicolegal Pitfalls

No medicolegal complications exist because granular parakeratosis is a benign condition whose symptoms include pruritus and, sometimes, a burning sensation. Additionally, ensure that the condition is not a bacterial or fungal condition or that a case clinically diagnosed as granular parakeratosis is not another inflammatory condition.

References

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

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

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

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

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

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

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

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

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

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

11. Pock L, Cermáková A, Zipfelová J, Hercogová J. Incidental granular parakeratosis associated with molluscum contagiosum. Am J Dermatopathol. Feb 2006;28(1):45-7. [Medline].

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

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

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

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

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

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

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

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

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

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

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

23. Barnes CJ, Lesher JL Jr, Sangueza OP. Axillary granular parakeratosis. Int J Dermatol. Jul 2001;40(7):439-41. [Medline].

24. Mehregan DA, Thomas JE, Mehregan DR. Intertriginous granular parakeratosis. J Am Acad Dermatol. Sep 1998;39(3):495-6. [Medline].

25. Srivastava M, Cohen D. Axillary granular parakeratosis. Dermatol Online J. 2004;10(3):20. [Medline].

26. Woodhouse JG, Bergfeld W. Granular parakeratosis. Pediatr Dermatol. Nov-Dec 2004;21(6):684. [Medline].

Keywords

axillary granular parakeratosis, intertriginous parakeratosis, AGP, GP

Contributor Information and Disclosures

Author

Noah S Scheinfeld, MD, JD, FAAD, Assistant Clinical Professor, Department of Dermatology, Columbia University; Consulting Staff, Department of Dermatology, New York Medical College-Metropolitan Hospital; Private Practice
Noah S Scheinfeld, MD, JD, FAAD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

Medical Editor

Peter Fritsch, MD, Chair, Department of Dermatology and Venereology, University of Innsbruck, Austria
Peter Fritsch, MD is a member of the following medical societies: American Dermatological Association, International Society of Pediatric Dermatology, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

Pharmacy Editor

David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Director, Division of Dermatology, Scott and White Clinic; Director Dermatology Residency Training Program, Scott and White Clinic
David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Managing Editor

Jeffrey J Miller, MD, Associate Professor, Department of Dermatology, Penn State University, Milton S Hershey Medical Center
Disclosure: Nothing to disclose.

CME Editor

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
Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

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