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] 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 developed this yellowish, scaly plaque at his left infra-axillary area after changing deodorants. Pathology confirmed granular parakeratosis. Courtesy of David F. Butler, MD.
Pathophysiology
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.
Etiology
The cause of granular parakeratosis is uncertain. Although controversial, the following have been implicated as etiologies for granular parakeratosis:
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Use of topical solutions or creams, in particular antiperspirants and deodorants [13]
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Presence of an occlusive environment
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Increased sweating
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Local irritants
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.
Epidemiology
Frequency
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]
International
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.
Race
No racial association has been reported for granular parakeratosis. 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.
The contention that white, middle-aged females are the primary group to experience granular parakeratosis was stressed in a 2013 article. [22]
Age
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]
Prognosis
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.
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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.
