(juvenile) pityriasis rubra pilaris

9
International Journal of Dermatology 2006, 45, 438–446 © 2006 The International Society of Dermatology 438 Blackwell Publishing, Ltd. Oxford, UK IJD International Journal of Dermatology 1365-4632 Blackwell Publishing Ltd, 2005 45 Education (Juvenile) Pityriasis rubra pilaris Sehgal and Srivastava Education (Juvenile) Pityriasis rubra pilaris Virendra N. Sehgal, MD, and Govind Srivastava, MD From the Dermato-Venereology (Skin/VD) Centre, Sehgal Nursing Home, Delhi, and Skin Institute and School of Dermatology, Greater Kailash, New Delhi Correspondence Virendra N. Sehgal, MD, FAMS, FNASc, FRAS(Lond.) A/6 Panchwati, Delhi-110033, India E-mail: [email protected] Introduction Pityriasis rubra pilaris (PRP) comprises a group of chronic disorders displaying circumscribed follicular keratosis with palmoplantar keratoderma. 1,2 Both familial and acquired forms have been recognized. The former is infrequent and usually occurs in childhood. The bi- or trimodal distribution with regard to age usually involves a peak case incidence in the first and second decades. 3–5 Despite a significant peak in young children, there is a paucity of reports in this age group. 6,7 Hence, it was considered to be worthwhile to review PRP, using a Medline search of the past four decades (1966 –2004), in order to establish a consensus on this entity. Historical After the initial description of the disease in 1835, 8 occasional reports were noted, 9 until Besnier 10 coined the term “pityri- asis rubra pilaris” in 1889 (presently in vogue). The familial form of PRP was thought to be quite uncommon until De Beurmann and Bith, 11 in 1910, described the familial occur- rence of PRP for the first time. Recent studies have recorded familial occurrence in up to 6.5% of patients. 5,6,12–14 In a significant study of PRP comprising 29 children, Gelmetti et al . 6 failed to reveal a family history. A family history was found in two of 30 PRP patients in a study by Allison et al . 7 Epidemiology The exact proportion of affected children amongst PRP patients varies from study to study. Nevertheless, several reports have clearly demonstrated that the entity has three distinct age groups of peak occurrence, namely early child- hood (0–10 years), late childhood (11–19 years), and adult- hood (40–60 years). 3–5,15–22 Furthermore, in childhood, males are affected more often than females (male to female ratio, 3 : 2), 7 unlike adult PRP in which males and females are affected equally. Differences in PRP can be seen in different races. The PRP prevalence varies from 1 in 5000 to 1 in 50,000 in various populations. 3,23 Classification The classification of PRP is based on age at onset, behavior, clinical appearance, and prognosis (Table 1). Griffiths 3,24 described juvenile classical (type III), juvenile circumscribed (type IV), and juvenile atypical (type V) PRP occurring exclus- ively in children. Juvenile classical (type III) PRP is clinically similar to classical adult (type I) PRP, except that it occurs in children. Its progress is more favorable in children than in adults. 3 Juvenile circumscribed (type IV) PRP is a common form of PRP seen in children, with localization of the lesions on the knees and elbows. 3,25–27 In contrast, juvenile atypical (type V) PRP has more or less ichthyosiform features. Although rare, there have been reports that the juvenile classical form (type III) may later develop into the juvenile circumscribed form (type IV). The familial form of PRP in children is similar to the atypical adult form (type II). Although this classification of PRP is recognized globally, other classifications have been proposed. Gelmetti et al . 6 Table 1 Classification of pityriasis rubra pilaris 3 Clinical type Lesion distribution Natural course I. Classical adult Generalized Remission in 3 – 4 years II. Atypical adult Generalized Chronic intractable III. Juvenile classical Generalized Remission in 1–2 years IV. Juvenile circumscribed Localized Unpredictable V. Juvenile atypical Generalized Chronic intractable

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International Journal of Dermatology

2006,

45

, 438–446 © 2006

The International Society of Dermatology

438

Blackwell Publishing, Ltd.Oxford, UKIJDInternational Journal of Dermatology1365-4632Blackwell Publishing Ltd, 200545

Education

(Juvenile) Pityriasis rubra pilarisSehgal and SrivastavaEducation

(Juvenile) Pityriasis rubra pilaris

Virendra N. Sehgal,

MD

, and Govind Srivastava,

MD

From the Dermato-Venereology (Skin/VD) Centre, Sehgal Nursing Home, Delhi, and Skin Institute and School of Dermatology, Greater Kailash, New Delhi

Correspondence

Virendra N. Sehgal,

MD

,

FAMS

,

FNAS

c,

FRAS

(

L

ond.) A/6 Panchwati, Delhi-110033, India E-mail: [email protected]

Introduction

Pityriasis rubra pilaris (PRP) comprises a group of chronicdisorders displaying circumscribed follicular keratosis withpalmoplantar keratoderma.

1,2

Both familial and acquiredforms have been recognized. The former is infrequent andusually occurs in childhood. The bi- or trimodal distributionwith regard to age usually involves a peak case incidence inthe first and second decades.

3–5

Despite a significant peak inyoung children, there is a paucity of reports in this age group.

6,7

Hence, it was considered to be worthwhile to review PRP,using a Medline search of the past four decades (1966–2004),in order to establish a consensus on this entity.

Historical

After the initial description of the disease in 1835,

8

occasionalreports were noted,

9

until Besnier

10

coined the term “pityri-asis rubra pilaris” in 1889 (presently in vogue). The familialform of PRP was thought to be quite uncommon until DeBeurmann and Bith,

11

in 1910, described the familial occur-rence of PRP for the first time. Recent studies have recordedfamilial occurrence in up to 6.5% of patients.

5,6,12–14

Ina significant study of PRP comprising 29 children, Gelmetti

et al

.

6

failed to reveal a family history. A family historywas found in two of 30 PRP patients in a study by Allison

et al

.

7

Epidemiology

The exact proportion of affected children amongst PRPpatients varies from study to study. Nevertheless, severalreports have clearly demonstrated that the entity has threedistinct age groups of peak occurrence, namely early child-hood (0–10 years), late childhood (11–19 years), and adult-hood (40–60 years).

3–5,15–22

Furthermore, in childhood, malesare affected more often than females (male to female ratio,

3 : 2),

7

unlike adult PRP in which males and females areaffected equally. Differences in PRP can be seen in differentraces. The PRP prevalence varies from 1 in 5000 to 1 in50,000 in various populations.

3,23

Classification

The classification of PRP is based on age at onset, behavior,clinical appearance, and prognosis (Table 1). Griffiths

3,24

described juvenile classical (type III), juvenile circumscribed(type IV), and juvenile atypical (type V) PRP occurring exclus-ively in children. Juvenile classical (type III) PRP is clinicallysimilar to classical adult (type I) PRP, except that it occurs inchildren. Its progress is more favorable in children than inadults.

3

Juvenile circumscribed (type IV) PRP is a commonform of PRP seen in children, with localization of the lesionson the knees and elbows.

3,25–27

In contrast, juvenile atypical(type V) PRP has more or less ichthyosiform features.Although rare, there have been reports that the juvenileclassical form (type III) may later develop into the juvenilecircumscribed form (type IV). The familial form of PRPin children is similar to the atypical adult form (type II).Although this classification of PRP is recognized globally,other classifications have been proposed. Gelmetti

et al

.

6

Table 1 Classification of pityriasis rubra pilaris3

Clinical type Lesion distribution Natural course

I. Classical adult Generalized Remission in 3–4 yearsII. Atypical adult Generalized Chronic intractableIII. Juvenile classical Generalized Remission in 1–2 yearsIV. Juvenile circumscribed

Localized Unpredictable

V. Juvenile atypical Generalized Chronic intractable

© 2006

The International Society of Dermatology International Journal of Dermatology

2006,

45

, 438–446

439

Sehgal and Srivastava

(Juvenile) Pityriasis rubra pilaris

Education

endeavored to delineate the entity into three types based pri-marily on the duration of the disease, absence of any correla-tion between the extent of the disease, juvenile conformingeither to localized or generalized PRP.

28–30

Piamphongsantand Akaraphant,

14

on the other hand, classified the diseaseinto four types based only on the physical (morphologic)findings. Miralles

et al

.

31

recorded PRP in association withhuman immunodeficiency virus (HIV) infection. The mor-phologic features (nodulocystic/lichen spinulosus) weresufficiently distinct to classify it as the atypical adult form(type II) and there was a chronic intractable course.

3

Etiology

The etiology of PRP in children is similar to that in adults.

1,2,25

Certain salient features should be reviewed. The deficiency orabnormal metabolism of vitamin A continues to be a debat-able cause of PRP in children. The efficiency of retinoids in thetreatment of PRP points to the probable role of vitamin Ametabolism.

32–40

Rothman

41

observed that systemic vitamin Aor its topical administration was a beneficial adjunct in fol-licular and/or nonfollicular hyperkeratosis of PRP. The widelyreported association of PRP with autoimmune disordersmay point to a probable underlying immunologic abnormal-ity.

42–52

Shvelli

et al

.

53

recorded enhanced spontaneousactivity of T-suppressor cells, with an impairment of T-helperfunctions, in a 6-year-old child with PRP. Hypogammaglob-ulinemia

54

and isolated IgA deficiency

55

have also beenrecorded in juvenile PRP. Circumscribed juvenile-onset PRPwas recorded in two patients with Down’s syndrome, one ofwhom also had vitiligo.

56,57

HIV-infected individuals withPRP may be representative of a unique “HIV-associatedfollicular syndrome.”

31,58–60

The latter may also have nodulo-cystic acne, hidradenitis suppurativa, dissecting folliculitis ofthe scalp, and lichen spinulosus-like eruption.

31,60,61

The pre-cipitating events can sometimes be identified. Of the 57 PRPpatients reported by Davidson

et al

.,

5

five had an explicithistory of preceding trauma or infection. Significantly, allwere children. A history of preceding febrile illness was alsorecorded by Gelmetti

et al

.

6

in a series of 29 children.Similarly, Lareque

et al

.

62

observed that three of their fourcases of juvenile PRP occurred after an infection. Geneticfactors have been considered to be important.

63

The patternof inheritance by and large is autosomal dominant with vari-able expressivity.

1,2

Autosomal recessive inheritance has alsobeen recorded.

64

Monozygotic twins have been reported todevelop PRP.

65

Clinical Features

Amongst children, the juvenile classical form (type III) is themost common expression of PRP.

1,2

The onset of the conditionis gradual in the familial type, whereas it is quite rapid in the

acquired types. Allison

et al

.

7

recorded 17 juvenile classical(type III), 10 juvenile circumscribed (type IV), and one juvenileatypical (type V). The other two patients in this study hadmixed features.

Juvenile classical (type III)

The onset of this form is usually at the age of 5–10 years, andits clinical features are identical to those of classical adult PRP(type I). Usually, the lesions start on the head, neck, or uppertrunk. Erythematous, scaly macules soon develop follicularand/or perifollicular papules; a central acuminate keratoticplug is conspicuous (Fig. 1). Ultimately, the papules coalesceto form sheets of erythema-studded acuminate papules, typic-ally spreading in a cephalocaudal direction. Hyperkeratosisof the palms and soles is a prominent feature, as is the bran-like scaling of the scalp. Erythroderma/exfoliative dermatitismay occasionally supervene to complicate the clinical pic-ture.

6,62,66,67

Acute infection or trauma may initiate or precip-itate the condition. At times, partial healing of the lesions mayresult in the transformation of the juvenile classical (type III)form to the juvenile circumscribed (type IV) form.

Juvenile circumscribed (type IV)

This form is usually seen in the later part of the first decade oflife. It is characterized by the formation of well-circumscribed,erythemato-squamous plaque(s) studded with follicular and/or nonfollicular papules. Keratotic plugging is prominent.The lesions are largely confined to the elbows and knees(Fig. 2). A careful naked eye scan of the skin surface inbroad daylight may reveal occasional erythematous scalymacules/papules over the trunk or the scalp. In due course,the palms and soles may develop mild to moderate kerato-derma. The clinical course of the disease is marked by remis-sions and exacerbations, and may ultimately heal in the lateteens.

1,2,7

Juvenile atypical (type V)

This is a fairly uncommon subtype. Its clinical expression isrevealed through erythema and/or hyperkeratosis. It eitherappears at birth or a couple of years later. It is characterizedby mild to severe erythema, follicular plugging, and kerato-derma. It is imperative to differentiate the condition from anichthyotic disorder. Scleroderma-like changes affecting thedigits may be apparent. Familial trait might be an alarmingfeature.

PRP and HIV/acquired immunodeficiency syndrome (AIDS)

It is relevant to discuss PRP

vis-à-vis

HIV/AIDS, as an increas-ing number of children are becoming its inadvertent victims.Occasionally, an erythema resembling PRP has been recordedin infected children. A filiform pattern of keratosis affectingthe face and trunk is the cardinal feature, often associatedwith marked acne conglobata.

1,31,58–61

International Journal of Dermatology

2006,

45

, 438–446 © 2006

The International Society of Dermatology

440 Education

(Juvenile) Pityriasis rubra pilaris

Sehgal and Srivastava

The nail changes of juvenile PRP include distal yellow–brown discoloration, subungual hyperkeratosis, thickeningof the nail plates, and splinter hemorrhages.

1,2,6,7,68,69

Allison

et al

.

7

recorded the involvement of the nail plate in one-third

of the affected children in their series. The hair and teeth areusually unaffected. Mucous membrane involvement is onlyobserved occasionally, and shows a diffuse whitish appear-ance of the buccal mucosa.

70

Course and Complications

Juvenile classical PRP (type III) usually runs a benigncourse.

1,2,71–74

Some cases have recorded partial clearing and achange to the type IV form. Spontaneous clearing may be seenafter 1–2 years. Juvenile circumscribed PRP (type IV), how-ever, has an uncertain prognosis, as a proportion of casesclear by the late teens. On the other hand, juvenile atypicalPRP (type V) shows more tendency to clear spontaneously,and is often resistant to treatment. Familial types frequentlypersist throughout life.

1,6,7

Allison

et al

.

7

reported the development of erythrodermain 17% of affected children, while 13% showed ectropion.Gelmetti

et al

.,

6

on the other hand, observed no instances oferythroderma or ectropion in their long-term study of 29 chil-dren with PRP. Photosensitivity and worsening with UV-Aand UV-B have also been reported.

75–77

Figure 1 Pityriasis rubra pilaris. Erythematous scaly macules, follicular and/or perifollicular papules, and a central conspicuous acuminate keratotic plug affecting the head (a), neck, upper trunk (b), and dorsa of the hands (c)

Figure 2 Pityriasis rubra pilaris. Well-circumscribed erythemato-squamous plaque(s) studded with follicular and/or nonfollicular papules

© 2006

The International Society of Dermatology International Journal of Dermatology

2006,

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, 438–446

441

Sehgal and Srivastava

(Juvenile) Pityriasis rubra pilaris

Education

Histopathology

The classical juvenile PRP histology is similar to that of clas-sical adult PRP. The histologic changes may differ from siteto site. A single skin biopsy from the representative lesion(follicular/nonfollicular) may help to resolve the dilemma to aconsiderable extent. It is therefore opportune to ascertain anddelineate the histologic criteria for the diagnosis of PRP with aproviso that they only supplement and do not supplant the clin-ical diagnosis.

78,79

The criteria include alternating orthokeratosisand parakeratosis in both vertical and horizontal directions;focal or confluent hypergranulosis; thick suprapapillary plates;broad rete ridges; narrow dermal papillae; and sparse superficialperivascular infiltration, mostly of lymphocytes. Plugging offollicular infundibula by cornified cells is seen only in biopsyspecimens that come from lesions that are clinically indubitablyfollicular.

1,80

Occasionally, focal area(s) of plasma exudates,neutrophilic infiltrate, and bacterial colonies may appear inthe keratin layer. They may indicate an acute and/or infectedepisode. Psoriasis has many histologic features in commonwith PRP, but evolving and fully developed lesions of psori-asis contain neutrophils in mounds of parakeratosis, thin reteridges, thin suprapapillary plates, broad dermal papillae, andmixed inflammatory cell infiltrates of variable density.

Juvenile circumscribed PRP may reveal a dense lamellatedhyperkeratosis, a normal or increased granular cell layer, anda mild acanthosis. A sparse histiocytic cellular infiltrate andminimal capillary dilatation may also be seen.

2,25

Sodiumdodecylsulfate polyacrylamide gel electrophoresis indicates aspecific pattern of keratin components, markedly in contrastwith that found in psoriasis.

81

This differentiates this localizedform from psoriasis. In addition, neutrophil microabscessesare conspicuous by their absence.

2,82

In familial PRP, Western blot analysis of the skin revealskeratin 17 expression, which has been found in psoriatic skinand in basal cell carcinoma. Keratin 6 and 16 are alsoexpressed, indicating keratinocyte activation.

63

A recent addition to the histopathology of classical PRP isthe observation of acantholysis and focal acantholytic dys-keratosis.

78,83–85

Magro and Crowson

78

recorded acantholyticdyskeratosis in 23 of 32 biopsies from PRP patients, whereasit was absent in 23 psoriatic controls. This particular findingmay be an important future tool for distinguishing betweenPRP and psoriasis. The preceding descriptive characteristicsare comprehensively shown in Figs 3–6.

Differential Diagnosis

The localized and classical form of juvenile PRP may often bemistaken for psoriasis; however, its bimodal age at onset, fur-furaceous scaling on the scalp, keratoderma with islands ofpale skin, and “islets of sparing” distinguish it from psori-asis.

2

Histopathologically, juvenile circumscribed PRP appears

more psoriasiform than the classical juvenile form, but lacksMunro microabscesses.

25

Walsh

et al

.,

86

after a detailedassessment of biopsy specimens from erythroderma patientsby several dermatopathologists, found only 25% diagnosticaccuracy in the assignment of PRP.

Juvenile circumscribed PRP should also be differentiated fromerythrokeratodermas, such as Gottron’s syndrome.

2

Juvenile

Figure 3 Biopsy showing an irregular epithelial hyperplasia with striking, almost ichthyotic, orthohyperkeratosis with minimal parakeratosis. In addition, there is suprabasilar acantholytic dyskeratosis, a highly characteristic finding in pityriasis rubra pilaris. There is a moderately dense superficial inflammatory cell infiltrate, a finding not uncommon in pityriasis rubra pilaris, which points to underlying immune dysregulation in some patients (hematoxylin and eosin, ×200)

Figure 4 Psoriasiform hyperplasia. Unlike psoriasis, the granular cell layer is notably increased and some epidermolytic hyperkeratosis is seen. In addition, the epidermis is surmounted by a markedly thick, almost ichthyotic, hyperkeratotic stratum corneum which is dominated by orthohyperkeratosis with only minimal parakeratosis. The classical psoriatic capillary changes are not seen (hematoxylin and eosin, ×100)

International Journal of Dermatology

2006,

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, 438–446 © 2006

The International Society of Dermatology

442 Education

(Juvenile) Pityriasis rubra pilaris

Sehgal and Srivastava

atypical PRP may be confused with other poorly definedichthyotic disorders, including follicular ichthyosis and eryth-rokeratodermas,

87

both early and late in the course of the disease.There are difficulties in the clinical and histologic diagnosis ofthe disease with full confidence. Thus, repeated observationsand a number of biopsies are recommended for the diagnosis.

2

Some investigators believe that acute juvenile PRP is areactive exanthem, and is mediated by bacterial super-antigens.

16,88,89

Betlloch

et al

.

16

recorded that PRP in these patientsfollowed an infectious condition, had a characteristic clinicalcourse, and the patients recovered satisfactorily. Further-more, at this juncture, it is worthwhile revisiting the salientfeatures of a few common follicular dermatoses, which mustbe considered in the differential diagnosis of PRP (Table 2).

90

Treatment

Juvenile PRP has been treated using vitamin A, syntheticretinoids, diet supplements, and intensive and varied topicaltherapy.

1,2,25,93–99

General nutrition and healthcare should be a commondenominator in all children when treating the disease. Oralvitamin A, cod liver oil, halibut liver oil, vitamin E, and caro-tene have all been tried with variable results.

1,2,25

The benefitsof topical vitamin A have also been recorded.

100

The advent of synthetic retinoids has brought about arevolution in the therapy of juvenile PRP, especially in recalci-trant cases.

25,96–103

Isotretinoin at a dosage of 1–2.2 mg/kg/day for 12–16 weeks has been proven to be beneficial.

95,101

Etretinate has also been shown to be beneficial at a dosage of0.5–1 mg/kg/day for 3–5 months.

96,97

The duration of remis-sion is variable, however, and recurrences do occur. The side-effects of oral retinoids can warrant the discontinuation oftherapy in children.

Other treatment modalities include methotrexate,

104,105

cyclosporine A,

106,107

stanozolol,

108

penicillin,

109

and anti-tubercular drugs.

109

Narrow-band UV-B with oral retinoids hasalso been useful in some cases.

110,111

Topical calcipotriol

112

and tacalcitol

113

have also given promising results. Synergismof vitamins A and E has also been made use of in PRP.

114

Table 2 Pityriasis rubra pilaris: differential diagnosis

Inheritance and age of onset Distribution Clinical features

Association/course Histology

Pityriasis rubra pilaris Adults, 1st decade/40–60 years

Localized/universal Scalp scaling, erythroderma, keratoderma, islands of sparing, nutmeg grater feel of papules

Lichen planus, vitiligo Persistent course

Classically, follicular plugging, parakeratotic, perifollicular shoulder, checkerboard pattern of orthokeratosis and hypogranulosis

The salient clinical features of pityriasis rubra pilaris are required to be differentiated from those of a few folliculardermatoses, the details of which are given belowKeratosis Adults, Extensors Perifollicular Atopy, ichthyosis Follicular plug withpilaris childhood, erythema, antenna Decrease with twisted hair within it

adolescence sign, coiled hair within horny plug

summer and age

Follicular psoriasis Variable, 2nd decade

Extensor/trunk Scalp scaling, increased nail growth, pitting, onycholysis, scaly follicular eruption coalescing to plaques

Remissions and relapses

Hyperkeratosis, parakeratosis, hypogranulosis, regular acanthosis, Munro microabscesses

Lichen spinulosus Childhood Extensor/ Crops of follicular Self-limiting Hyperkeratosis withtrunk/fossae papules with keratinous spines follicular plugging

Darier’s Adults, Seborrheic Greasy, malodorous Summer increase Suprabasal(Darier–White) disease/keratosis follicularis91

10–20 years areas and flexures follicular papules Acrokeratosis verruciformis ofHopf

Steroids aggravateChronic/persistent

acantholysis Corps ronds and grains

Pits on the palm Nail (white, red bands, V nick)

Phrynoderma Any age, commonly childhood

Elbow, thigh Monomorphic, pigmented, follicular papules

Vitamin A deficiency Curable

Hyperkeratosis with follicular plugging

Lichen Childhood, Trunk, proximal Grouped, scaly, TB lymph node, bone Perifollicularscrofulosorum92 2nd−3rd decade extremities asymptomatic, acuminate,

lichenoid follicular papules Adequate treatment/cure

tuberculoid granuloma

© 2006

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2006,

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, 438–446

443Sehgal and Srivastava (Juvenile) Pityriasis rubra pilaris Education

HIV-associated PRP is more recalcitrant to therapy.Highly active triple anti-retroviral drug therapy has showna positive response60 in alleviating the symptoms and maycause complete regression in such patients. Antiretroviraldrug therapy has shown a positive response in alleviatingthe symptoms, and may cause complete regression in suchpatients.60

Acknowledgments

It is a privilege to acknowledge Dr Cynthia Magro for the out-standing photomicrographs (Figs 3–6) from her collectionwhich strengthen the text of this article.

References

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2 Griffiths WAD, Judge MR, Leigh IM. Pityriasis rubra pilaris. In: Champion RH, Burton JL, Burton DA, eds. Textbook of Dermatology. Edinburgh: Blackwell Science, 1998: 539–1545.

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Figure 5 The epidermis is surmounted by a very thick stratum corneum that shows orthohyperkeratosis with small foci of intervening parakeratosis. The granular cell layer shows prominent keratohyaline granules with a variable disposition to the cytoplasmic membranes, resulting in perinuclear vacuolar change, another characteristic feature of pityriasis rubra pilaris. In contrast, the granular cell layer is diminished in psoriasis (hematoxylin and eosin, ×100)

Figure 6 Characteristic follicular plugging. Orthohyperkeratosis and preservation and increase of the granular cell layer are also seen (hematoxylin and eosin, ×100)

International Journal of Dermatology 2006, 45, 438–446 © 2006 The International Society of Dermatology

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