Received on August 12, 2004.Approved by the Consultive Council and accepted for publication on January 06, 2006.* Work done at Pediatric Dermatology Service at the Pediatrics Department - Hospital de Clínicas/Universidade Federal do Paraná - UFPR - Paraná (PR),Brazil.Conflict of interests: None
1 Masters in Pediatrics and Doctor at Pediatric Dermatology Service, Hospital de Clínicas, Universidade Federal do Paraná - UFPR - Paraná (PR), Brazil.2 Masters in Pediatrics and Assistent Professor of Pediatric Dermatology Service, Hospital de Clínicas, Universidade Federal do Paraná - UFPR - Paraná (PR), Brazil.3 Ph. D in Pediatrics - Universidade Federal do Paraná - UFPR - Paraná (PR), Brazil.4 Pediatrician - Universidade Federal do Paraná - UFPR - Paraná (PR), Brazil.5 Head of the Pediatric Dermatology Service, Hospital de Clínicas, Universidade Federal do Paraná - UFPR - Paraná (PR), Brazil.6 Pathologist and post-graduate student at Pediatric Dermatology Service, Hospital de Clínicas, Universidade Federal do Paraná - UFPR - Paraná (PR),
Brazil.7 Masters and Dermatopathologist at Patology Service,, Hospital de Clínicas, Universidade Federal do Paraná - UFPR - Paraná (PR), Brazil.
Abstract: Granular parakeratosis is an alteration of keratinization that was first described in adults. It ischaracterized by hiperkeratotic plaques and papules in intertriginous areas. The authors describe sixcases of granular parakeratosis in children. One patient had lesions on the buttocks; two children pre-sented papules in both axillae and cervical region (presentations never described before in the litera-ture). The remaining three patients presented with lesions in the inguinal folds. Review of the literatureand discussion on the pathogenesis of this rare dermatosis are presented.Keywords: Child; Epidermis; Keratinocytes; Patology
Resumo: A paraqueratose granular é alteração da queratinização, primeiramente descrita em adul-tos, caracterizada por pápulas e placas hiperqueratósicas nas áreas intertriginosas. Os autoresdescrevem seis casos de paraqueratose granular em crianças. Um paciente apresentava lesões nasregiões glúteas, dois em ambas as axilas e região cervical (apresentações inéditas na literatura). Trêspacientes apresentavam lesões em pregas inguinais. Realizam também revisão da literatura e dis-cutem a possível etiologia dessa rara dermatose.Palavras-chave: Ceratinócitos; Criança; Epiderme; Patologia
An Bras Dermatol. 2006;81(1):59-64.
Caso Clínico59
INTRODUCTIONGranular parakeratosis (GP) consists of the
presence of brown-redish hyperkeratotic papullaeand plaques, with a size ranging from three to fourmilimeters, located in intertriginous areas.1,2 It hasbeen first described in the axillary folds of adults,3-6
being later observed in other cutaneous folds, such assub and intermammary,1,7 abdominal,1 inguinal1,2,4 andperianal1 ones. Later on, GP was also observed inchildren with lesions in the perianal area and folds.2,8-
11
GP is considered to be an alteration of kera-tinization, and likely causes are still only hypotheti-cal.1,4,12 Lesions, which might have a six-month evolu-tion, are generally assymptomatic or little pruritic,
with spontaneous involution or regression followingapplication of several types of topic medications.4
The authors here describe six cases of GP inchildren, the first one presenting with lesions in thegluteus region, the second in the axillary folds bilat-erally, the third in the cervical region, and the othersin the inguinal folds. Bilateral axillary and cervicalpresentations are unprecedented in literature for thepediatric age range.
CASE REPORTSCase 1
Male patient, dark skin, 10-months old. Hehad been presenting with brownish plaques in the
gluteus and diaper-covered regions for twomonths (Figure 1). For the prevention of dermati-tis in the diaper region, he had been using dailyaplications of zinc oxide ointment with vitamins Aand D and boric acid. On examination, presentedscales forming brownish and hyperkeratoticplaques from 1 to 3 mm wide, grouped in the glu-teus region, leaving a slight depression whenremoved with a curet. Histopathology of the scalesremoved by curettage revealed a hyperkeratosiswith intense parakeratosis and the presence ofinumerous dark granules (keratohyalin granules).PAS and Giemsa stains were negative.
Case 2Female patient, dark skin, aged nine months.
Fifteen days before, she had the onset of dark brown
circular scales with a diameter varying from 1 to 4 mmin diameter, forming plaques in the axillary regions,bilaterally (Figure 2). When curetted, the scales left asmall depression on the site. Patient had used an oint-ment containing zinc oxide, bismuth, aubgalate, mag-nesium and diiodothymol. When treated with topicalsalicylic acid cream at 5%, had a complete remissionof the lesions in two weeks. Histological examinationof a sample collected by curettage revealed keratinwith extense parakeratosis and the presence of vari-ous dark granules (Figure 3), PAS-CD and Giemsanegative.
Case 3Eight month-old white female patient had been
presenting yellow-brownish papules bilaterally in thecervical region for seven months (Figure 4). Past his-
An Bras Dermatol. 2006;81(1):59-64.
60 Giraldi S, Abagge KT, Carvalho VO, Muller S, Marinoni LP, Werner B, Fillus Neto J.
FIGURE 1: Brown keratotic papules in the gluteus region FIGURE 3: Scales curetted from axillary regions displaying hyperk-eratosis, intense parakeratosis and numerous dark keratohyalin
granules (HE magnification 40X)
FIGURE 2: Brown keratotic papules in the axillae (detail left axilla) FIGURE 4: Light brown papules and scales in cervical region
An Bras Dermatol. 2006;81(1):59-64.
tory of sudamina in the cervical region with the use oftalc powder. As in the previous treatment, topic low-potency steroids were prescribed, with no improve-ments. Moreover, she presented a café-au-lait spot inthe scapulary region, a salmon spot in the glabella,back of the nose and nucha, and some teleangiec-tasias and flebectasias in the left lower limb, with nosigns of atrophy or cutaneous depressions, makingthese lesions clinically compatible with congenitalteleangiectatic cutis marmorata. Treatment with ther-mal water was instituted for sudamina, along with sal-icylic acid cream at 4% for two weeks for the scales.There was a complete disappearance of the lesions.
Case 4Two year-old asian male patient with the onset
of brownish desquamating crusts bilaterally in theinguinal folds two weeks before (Figure 5). Underexamination, presented with small brownish scalesmeasuring from 2 to 3 mm in diameter, formingplaques in the inguinal region. Lesions left a smalldepression on their base when excised with a curet. Aspast medical history, had achondroplasia and variousepisodes of diaper dermatitis and of perianal candidi-asis. Made regular use of zinc oxide, boric acid and vit-amins A and D ointment, as well as nistatin ointmentand disposable diapers. Following curettage of thelesions, anatomopathological examination revealedthe presence of granular parakeratosis (Figure 6). Hewas treated with salicylic acid at 3% in a lanette base,in a single application after bathing. Weobserved com-plete disappearance of the lesions after 14 days oftreatment.
Case 5White six month-old male patient, who had had
dark brown scales in the inguinal folds for twomonths. He had been a premature child, with an oth-erwise uneventful medical history. His mother hadbeen treated with progesterone during the secoondtrimester of her pregnancy. Positive family history foratopy. Regular use of an ointment containing zincoxide, boric acid, vitamins A and D, benzalconiumchloride and cetrimonium bromide in the perineum.Under examination, presented with brownish scalesforming small plaques of 2 or 3 cm in the inguinalfolds and suprapenian region. Scales dettached easilyon curettage, leaving a slight depression on the site.He was treated with 3% salicylic acid in vaseline,applied daily on the lesions. The patient did notreturn for reevaluation.
Case 6White five month-old female patient, with the
onset of brown scales in the inguinal folds twomonths before. Examination revealed the presence ofbrownish scales going from 2 to 3 mm in diameter,which left a slight depression when removed with acuret. As in previous cases, she made regular use ofan ointment containing zinc oxide, boric acid and vit-amins A and D. When treated with a salicylic acidcream at 3% (in lanette) in a single application afterbathing, lesions remitted completely. She returned atthe age of eight years and four months still withabsence of either lesions or scars in the inguinal foldsbilaterally, presenting only ephelids in the face andxerosis.
FIGURE 5: Scales curetted from inguinal regions exhibiting darkkeratohyalin granules in horny layer (HE magnification 100X)
FIGURE 6:Brownishscales ininguinalregions
Granular parakeratosis: a report of six cases in children 61
An Bras Dermatol. 2006;81(1):59-64.
62 Giraldi S, Abagge KT, Carvalho VO, Muller S, Marinoni LP, Werner B, Fillus Neto J.
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DISCUSSIONIn 1999, Northcutt and his collaborators
described four cases of a new entity, naming it axillarygranular parakeratosis. The lesions, located in the axil-lae, were characterized by hyperpigmented or erythe-matous plaques, either uni or bilateral, and pruritic.Histology demonstrated the presence of hyperparaker-atosis with keratohyalin granules restricted to thehorny layer.3 This dermatosis is acquired and charac-terized by the presence of multiple brownish or red-brownish hyperkeratotic plaques ranging from three tofour millimeters, occasionally forming plaques locatedin the intertriginous areas.1,2 ALesions are asympto-matic or little pruritic, lasting for months or undergo-ing spontaneous involution. Regression of GP mayoccur with the use of numerous topic medications.4
The first description was followed by others, of lesionsin the axillae1,3-6 and also in submammary and inter-mammary,1,7 inguinal1,2,13 and perianal1 folds. Theexpression intertriginous granular parakeratosis seemsthe most adequate, since GO can occur in cutaneousfolds other than the axillary.4 In Brazil, the first report-ed case was in an adult female with lesions in the sub-mammary region.14
The first pediatric case reported in literaturewas that of a child presenting with lesions bilaterallyin the inguinal region, with a history of topical use ofvarious products on the affected site.2 Six other caseswere reported in children ranging from 10 to 24months of age.9,11 The first case described in the pedi-atric age with lesions in left axilla had past history ofuse of roll-on deodorant.10 Of the three more recentcases, two presented erythema under the scales, andauthors have suggested two clinical patterns of pre-sentation, one with linear scales and the other associ-ated with erythema.8
Etiology of GP is still undetermined. There isan hypothesis that states that the basic defect is in thetransformation of profilagrin into filagrin, resulting infailure to degrade keratohyalin granules and to aggre-gate keratine filaments during hornification.Abnormalities in cell surface structures and compo-nents of the horny envelope would then contribute tothe formation of retention hyperkeratosis.1
Physical factors such as hyperhydrosis, obesityand friction could contribute to its onset because ofmechanical irritation, which in its turn would pro-voke a protective response, determining epidermalproliferation with formation of abnormal granularcell layers.6 Irritating substances and toxic agentsseem to have an etiological implication in GP. Theuse of chemicals in soaps, deodorants (roll-on,stick), antiperspirants, shampoo, formulas, cosmeticand dermatological creams and ointments wouldincrease the number of transitional cells.1,7 Zinc
oxide, which is a component of ointments with pro-tective properties against diaper area dermatitis,would increase the rate of mitoses of cells in thebasal layer.12 Participation of microbial organismsand of Candida albicans has not been proven.1
On histology, GP presents a thick, paraketatot-ic and basophilic horny layer, as well as a discreteperivascular lymphocyte infiltrate, which may be dueto irritating factors. Electronic microscopy demon-strates a great amount of keratohyalin granules, andinfundibles present thick horny plugs with alterationssimilar to those occurring in the epidermis.6 Alsoreported are epidermal hyperplasia with a preservedgranulous layer, discrete perivascular T CD4+ lym-phocyte infiltrate in the upper dermis, absence ofdendritic CD1+ cells in the epidermis, as well as epi-dermal keratins (keratin 5/14,1/10) and normalinvolucrin expression. Horny layer cells are filled withbasophilic granules which are immunoreactive toantibodies that recognize filagrin and its precursor,which is a feature of GP.1
Differential diagnosis in the infant must bemade with keratotic affections which affect cutaneousfolds, such as verrucous nevus, acanthosis nigricans,confluent and reticular papilomatosis, seborrheicdermatitis, fungal infections, inverted-form psoriasis,Darier’s and Haley-Haley’s disease, and contact der-matitis.
Several topic agents are used in the treatmentof GP. Calciprotriene, pimecrolimus, topic steroids,topic and oral tretionine are all described.5,8
Spontaneous disappearing is reported in five cases inliterature.1
Including the ones here presented, there are17 GP cases described in children (Chart 1). Casesreported here are similar to those in literature con-cerning clinical presentation, evolution, site ofaffection in the pediatric age range, histopathologi-cal features and past history of use of ointmentscontaining zinc oxide. In the literature, eight caseshad used zinc oxide in the perineum, and in othertwo there were no specifications concerning the useof topical substances.
The authors support the hypothesis that dia-per friction, sweating and use of ointments contain-ing zinc oxide, together are irritating factors thatmay explain the onset of perineal lesions. In axillaryand cervical folds, the use of creams, soaps and talcpowder, the latter already contraindicated forinfants, could be implicated as triggering agents.Bilateral axillary and cervical affection (Cases 2 and3) was up to our knowledge not described in pedi-atric literature.
In cases 3, 5 and 6, diagnosis was based onclinical data and on the presence of small depres-
An Bras Dermatol. 2006;81(1):59-64.
Granular parakeratosis: a report of six cases in children 63
11. Pimentel DR, Michalani N, Morgado de Abreu MA, Petlik B, Mota de Avelar Alchorne M. Granular parakeratosis inchildren: case report and review of the literature.Pediatr Dermatol. 2003;20:215-20.
13. Mehregan DA, Thomas JE, Mehregan DR. Intertriginousgranular parakeratosis. J Am Acad Dermatol.1998;39:495-6.
14. Michalany N. Michalany N. Caso anátomo clínico [videocassete]. Belo Horizonte (MG): Sessão Anátomo-Clínica, 54º Congresso Brasileiro de Dermatologia, 1999.
15. Scheinfeld NS, Mones J.Granular parakeratosis:Pathologic and clinical correlation of 18 cases of granu-lar parakeratosis. J Am Acad Dermatol. 2005; 52 :863-7.
REFERENCES1. Metze D, Rütten A. Granularparakeratosis-a unique
acquired disorder of queratinization. J Cutan Pathol.1999;26:339-52.
2. Trowers AB, Assaf R, Jaworsky C. Granular Parakeratosisin a Child. Pediatr Dermatol. 2002;19:146-7.
3. Northcutt AD, Nelson DM, Tschen JA. Axillary granularparakeratosis. J Am Acad Dermatol. 1991;24:541-4.
4. Mehregan DA, Vandersteen P, Sikorski L, Mehregan DR. Axillary parakeratosis. J Am Acad Dermatol.1995;33:373-5.
5. Webster CG, Resnik KS, Webster GF. Axillary granular parakeratosis: Response to isotretinoin. J Am Acad Dermatol. 1997;37:789-90.
6. Rodriguez G. Axillary granular parakeratosis.Biomedica. 2002;22:519-23.
7. Wohlrab J, Lüftl M, Wolter M, Marsch WCh.Submammary granular parakeratosis: An acquiredpunctate hyperkeratosis of exogenic origin. J Am Acad Dermatol. 1999;40:813-4.
8. Chang M W, Kaufmann J M, Orlow S J, Cohen D E,Mobini N, Kamino H. Infantile granular parakeratosis:Recognition of two clinical patterns. J Am AcadDermatol. 2004; 50: S93-6.
9. Patrizi A, Neri I, Misciali C, Fanti PA. Granular parake-ratosis: four paediatric cases. Br J Dermatol.2002;147:1003-6.
10. Neri I, Patrizi A, Guerrini V, Fanti P A. GranularParakeratosis in a Child. Dermatology. 2003; 206:177-8.
sions in the site where scales over covered the skin,following curettage. It is important to highlightthat, in the small children, diagnosis can be madeby simple curattage instead of skin biopsy.15 Scalesare detached by using a curette, leaving tiny depres-sions in the base of the lesion, visible to the nakedeye, facilitating clinical diagnosis. Five of the casespresented here were treated with salicylic acid, atconcentrations going from 3 to 5%, with total remis-sion of the lesions in a few days. Use of classical ker-atolytics such as salicylic acid seems sufficient for acomplete resolution of the lesions.
Clinical presentation, use of ointments con-taining zinc oxide, curettage of the lesions andaccurate histopathological examination of scalesconfirmed the diagnosis of this rare entity. �
64 Giraldi S, Abagge KT, Carvalho VO, Muller S, Marinoni LP, Werner B, Fillus Neto J.
An Bras Dermatol. 2006;81(1):59-64.
ACKNOWLEGDMENTS To Pediatricians Dr. Mitsuru Miyaki and
Dr. Marcos Parolin Ceccatto and toDermatologist Dra. Marisa Cioli for the referralof the clinical cases.
