Granular Parakeratosis

Updated: Dec 13, 2019
Author: Sheevam A Shah, MD; Chief Editor: Dirk M Elston, MD 



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 has been associated with excessive use of topical preparations, in particular antiperspirants and deodorants, as well as exposure to chemical irritants found in antiseptics and household cleaning agents.[2, 3]

Granular parakeratosis is also associated with an occlusive environment, increased sweating, and, sometimes, local irritation. This association is strongly supported by a case in which eradication of an occlusive environment resolved granular parakeratosis lesions.[4] Some have linked it to obesity. New cases of granular parakeratosis continue to be reported involving different body regions.[5] Some suggest that granular parakeratosis has congenital links,[6] and others have considered if granular parakeratosis is a disease or a reactive process.[7] New cases are reported every year, and the disease is likely underdiagnosed.[8]

Note the image below.

Granular parakeratosis in an 82-year-old man who d Granular parakeratosis in an 82-year-old man who developed this yellowish, scaly plaque at his left infra-axillary area after changing deodorants. Pathology confirmed granular parakeratosis. Courtesy of David F. Butler, MD.


The etiology of granular parakeratosis is uncertain, but Metze and Rütten[9] 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.[10] 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.[11] Furthermore, a mouse model study demonstrated that exposure to aluminium chloride, a main active ingredient commonly used in antiperspirants, induced the development of histologically confirmed granular parakeratosis on mouse skin.[12] The aluminium-induced apoptosis led to the arrest of keratinization and promoted accelerated nuclear degeneration before profilaggrin could be processed to filaggrin. This could result in the retention of basophilic granules composed of profilaggrin in the stratum corneum of the mouse skin.

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


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 deodorants[13]

  • Presence of an occlusive environment

  • Increased sweating

  • Local irritants

  • Detergents containing benzalkonium chloride[2, 3]

Important to note is that because cases have been reported when these factors were not present, their importance is not clear.

In children, excessive washing has been noted in a series of 4 patients.[14]

In one case, a patient developed granular parakeratosis after treatment with triamcinolone for contact dermatitis.[15]

An occlusive environment demonstrated to play an important role in a woman with submammary granular parakeratosis whose lesions resolved with mastopexy, thereby eradicating a warm, moist, friction-prone region.[4]

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.



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[16] 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[16] 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.[17]


Few case reports of granular parakeratosis are noted, but it probably is not a rare condition. In Australia particularly, there has been a surge of reported cases of granular parakeratosis: in 2019, Flora and Whitfeld[18] reported a case of granular parakeratosis in a young male; in 2018, Shen et al[3] reported one case in an elderly woman; in 2017, Robinson et al[2] reported six cases of granular parakeratosis in children. Most recently, Demitsu et al,[19] in 2019, reported one case in a woman in Japan. In 2018, Keshavmurthy et al[20] reported one case in a woman in India. In 2002, Rodriguez[21] reported three 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.[22]


Granular parakeratosis has been reported in children,[14, 23] but it is mostly reported in women aged 40-50 years.[24] Cases reported in 2018 and 2019 describe the condition in elderly women aged 65-75 years.[3, 15, 25]


The prognosis for granular parakeratosis 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.




Patients typically 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 Mones[16] 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 al[26] 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.[14] Similarly, a report in 2012 from Chile noted granular parakeratosis occurring after axillary irritation due to an antiperspirant and perhaps the use of a zinc oxide paste, which resolved with calcipotriol and then reoccurred 2 years later in the patient, 20 kg greater in weight, in the bilateral axilla, with no presence of irritation but with use of the same antiperspirant.[27]

In 2019, Flora and Whitfeld[18] reported an unusual presentation of granular parakeratosis and concurrent red scrotum syndrome in a 27-year-old man. The patient presented with an exquisitely painful scrotal rash and bilateral hyperkeratotic plaques in the inguinal region.

In 2002, Rodriguez[21] reported three cases in obese women.

A number of incidental incidences of granular parakeratosis have been reported, including associations with dermatomyositis[28] and molluscum contagiosum.[29] 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.

Reddy et al noted a case of granular parakeratosis of 20 years’ duration.[30]

Granular parakeratosis can be unilateral.[31]

In children, it can be caused by topical products that impair the integrity of the skin and is thus perhaps more common in atopic skin.[2, 32]

Granular parakeratosis is a rare cause of vulvar dermatosis, accounting for 0.5% of cases in a series of 183 cases.[33]

Physical Examination

Granular parakeratosis manifests with intertriginous (ie, axillary, groin, intermammary or submammary region, and abdominal folds) bilateral or unilateral brown- or red-crusted patches, papules, or plaques. The primary lesions are keratotic brownish-red papules that can have a conical shape. They can coalesce into larger well-demarcated plaques with various degrees of maceration secondary to local occlusion. 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.[2] Granular parakeratosis can also occur in the groin area in adults.[18, 34] Granular parakeratosis has also been reported under the breast.[4, 25, 35] In one case, granular parakeratosis developed across the neck and anterior chest.[15]

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.[36]

Granular parakeratosis manifesting as facial keratotic papules has been reported.[37]

Genebriera et al[38] noted a papillomatous axillary rash due to granular parakeratosis.

Axillary red-brown bilateral plaques can be a manifestation of granular parakeratosis.[39]





Laboratory Studies

A potassium hydroxide preparation can be used to check for fungal infection.

Other Tests

A Wood lamp can be used to check for erythrasma.


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.[13] 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 DiLeonardo[40] described a follicular granular parakeratosis that was a granular parakeratosis confined to the follicle.

In 2004, Resnik et al[41] described dermatophyte-related granular parakeratosis.

Incidental granular parakeratosis has been associated with carcinomas,[42] dermatomyositis,[28] and molluscum contagiosum.[29]

Resnik et al[36] noted the existence of a granular parakeratotic acanthoma.

Yang et al (2012) noted granular parakeratosis of the eccrine ostia.[43]

A study in seven children found preservation of the nuclei and retention of keratohyalin granules from superficial scrapings, which could be used for a novel method of diagnosis.[32]



Medical Care

Although some consider granular parakeratosis rare, successful medical treatments have been reported. These have included topical corticosteroids and oral and topical retinoids.[44, 45]

A 2003 report notes that topical calcipotriene and ammonium lactate also effectively treated granular parakeratosis.[26]

Calcineurin inhibitors and topical antifungal agents have been tried with some success.

Isotretinoin[45, 46] and tretinoin[44] have been reported as effective for granular parakeratosis.

Calcipotriene has been used to treat granular parakeratosis.[47, 48] Additional vitamin D-3 analogs, such as maxacalcitol, have been used effectively for treatment.[19]

Owing to the association between granular parakeratosis and hyperhidrosis, one reported case showed use of injectable botulinum toxin to be an effective treatment for axillary granular parakeratosis.[49]

In biopsy specimens from psoriatic patients after and before acitretin, methotrexate, and phototherapy treatments, parakeratosis decreases, implying that these agents could be helpful for granular parakeratosis.[50]

Surgical Care

Rare reports have noted that cryotherapy and laser therapy[51] can effectively treat granular parakeratosis.

Although not a first-line consideration, surgical mastopexy has been shown to be an effective treatment in one refractory case of submammary granular parakeratosis.[4]


Patients should avoid excessive washing of intertriginous areas. They should minimize or avoid the use of roll-on deodorants and antiperspirants. Additionally, they should consider avoidance of antiseptics, household cleaning agents, and laundry detergents containing benzalkonium chloride if they are not responding to other methods.


Once granular parakeratosis resolves and the inciting substances are avoided, granular parakeratosis does not tend to recur. However, sometimes, granular parakeratosis 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.



Medication Summary

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

Maxacalcitol is an active vitamin D-3 ointment that has been used in refractory psoriasis. It seems to have potent antiproliferative and anti-inflammatory effects on keratinocytes and has been used effectively for treatment.[19]

Retinoid-like Agents

Class Summary

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.

Isotretinoin (Amnesteem, Claravis, Sotret)

Isotretinoin is an 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.

A US Food and Drug Administration–mandated registry is now in place for all individuals prescribing, dispensing, or taking isotretinoin. For more information on this registry, see iPLEDGE. This registry aims to further decrease the risk of pregnancy and other unwanted and potentially dangerous adverse effects during a course of isotretinoin therapy.

Tretinoin topical (Avita, Retin-A, Renova, Refissa, Tretin-X, Altreno)

Tretinoin topical makes keratinocytes in sebaceous follicles less adherent and easier to remove. It is available as 0.025%, 0.05%, and 0.1% creams. It is also available as 0.01% and 0.025% gels and 0.05% lotion. Tretinoin topical can be a first-line treatment in granular parakeratosis but is irritating and should be used with caution.

Tazarotene (Tazorac, Avage)

Tazarotene is a topical medication approved for psoriasis and acne. It is useful in normalizing functioning of epithelial cells. Tazarotene acts on a genetic level, leading to the transcription of certain retinoic acid genes. Use is off-label.

Vitamins, Fat-Soluble

Class Summary

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, Calcitrene)

Calcipotriene is a topical preparation containing vitamin D-3. It is indicated for psoriasis. Calcipotriene seems to normalize maturation of epidermal cells.

Topical Skin Products

Class Summary

This agent normalizes skin function.

Ammonium lactate (Lac Hydrin, AmLactin, LAClotion)

Ammonium lactate is a topical medication used to treat dry skin. It relieves itching and aids in healing skin in mild eczemas and dermatoses, itching skin, minor wounds, and minor skin irritations. Ammonium lactate is found in a variety of topical emollient lotions.


Class Summary

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 topical (CortaGel, Cortaid, Dermarest, Ala-Cort )

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