Erythroderma_generalized exfoliative dermatitis in pediatric practice_ an overview

EducationErythroderma/generalized exfoliative dermatitis in pediatric

practice: An overview

Virendra N. Sehgal, MD, and Govind Srivastava, MDFrom the Dermato-Venereology (Skin/VD) Center, Sehgal Nursing Home, Panchwati, Azadpur, Delhi, and Skin Institute Research Society, Greater Kailash, New Delhi, India

Correspondence

Prof. Virendra N. Sehgal, MD, FNASc, FAMS, FRAS(Lond.)

A/6, Panchwati

Delhi-110 033

India

E-mail: drsehgal@http://wendang.chazidian.com.in

Introduction

Erythroderma/generalized exfoliative dermatitis is a well-recognized entity in adults and it has been a focus of global1–8detailed dissertation. It is only occasionally that erythro-derma/exfoliative dermatitis in children (1–14 years) hasbeen the center of attention.9–12 Its intriguing clinical expres-sion in neonates and infants, in particular, and in children, ingeneral, posses a serious emergent challenge for the practicingpediatrician and dermatologist or pediatric dermatologist forits delicacy and life-threatening overture. Now it is absolutelyimperative to take stock of this entity in its entirety so that itsprecise diagnosis in addition to its management can be readilydevised to alleviate the anxiety of carers.

De?nition

The definition of erythroderma/exfoliative dermatitis in chil-dren is similar to that in adults wherein there is an involve-ment of total, or near total, body surface with erythema and/or moderate to extensive scaling. However, some disorders ininfants may initially be localized and then eventually developinto extensive erythema13 (Figs 1 and 2).

Incidence

Erythroderma is a rather uncommon situation in the pediatricage group, which has been borne out by recent studies,10where only 17 patients were recorded over a 6-year period.At the same time, its overall incidence was found to be 35 per100,000 amongst the total dermatologic out-patient popula-

tion in a cosmopolitan setting. A sample of 80 patients with

© 2006 The International Society of DermatologyFigure 1Erythroderma in a 3-day-old infantInternational Journal of Dermatology 2006, 45, 831–839831

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EducationPediatric erythrodermaFigure 2Erythroderma/exfoliative dermatitis following atopic

dermatitis

erythroderma contained only seven of the pediatric age group,

of which only three belonged to 0–3 years and a further 4–13 years of age, equating to an incidence of 8.8%. Male tofemale ratio was approximately equal, whereas age-at-onsetmay vary according to its etiology.

5 In a significant study com-prising neonatal and infantile (up to 1 year) erythroderma, itsincidence was found to be variable. The composition was30% in an immunodeficiency state, 24% in ichthyosis, 18%in Netherton’s syndrome, 20% had papulosquamous/eczematous dermatoses and a further 8% were idiopathic.11Etiology

Erythroderma/generalized exfoliative dermatitis possesses awide spectrum of etiology, and brief descriptions are shownin Table 1.13 There is an acute paucity of data comparing theincidence of various incriminated causes responsible forerythroderma/generalized exfoliative dermatitis (E/Gen).9–12In a recent study to investigate this aspect, drug-inducederythroderma was prominent at 29%, genodermatoses,

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Sehgal and Srivastava

psoriasis and Staphylococcal Scalded Skin syndrome (SSSS)at 18% each, atopic dermatitis at 12% and seborrhoeicdermatitis at 5%.

It is therefore incumbent to form the briefs of clinicalfeatures of the possible etiologic causes in order to pro-vide instant reading and to create awareness amongst non-dermatologists, physicians, pediatricians, gynecologists andneonatologists. Their endeavors should ultimately be pooledin order to form and consolidate the information aboutthe erythroderma/exfoliative dermatitis so that consensus isevolved to provide a better and more workable managementapproach for these patients.Clinical Features

This condition has infrequently been diagnosed in the recentpast.14–18 Nonetheless, the demonstration of abnormalhistiocytic-appearing cells in the skin, lymph nodes, spleen,and liver are significant. Erythroderma, failure to thrive,pronounced lymphadenopathy, and recurrent infections arethe salient clinical features. Marked leukocytosis, eosinophilia,anemia, hypogammaglobulinemia and depressed T-cellimmunity13 are its other supplements. T lymphocytesCD45RO+ may be demonstrated at the molecular level,16 anda skin biopsy may confirm the diagnosis16,18 and help in dif-ferentiating it from Netherton’s syndrome and Graft vs. hostdisease. Although it is mostly fatal. Cyclosporine and bonemarrow transplantation can be effective therapies.13,19

sequently develops fever, diarrhoea and rapidly progressivegeneralized exfoliative dermatitis (erythroderma), hypo-gammaglobulinemia has a dominant association. Monthlyreplenishment by intravenous infusion of gammaglobulinalleviates fever and erythema.20

ingly, are transfused with non-irradiated blood or havereceived small amount of maternal blood via placenta inutero. Usually these infants have primary immunodeficiency.Nonspecific morbilliform rash is its clinical presentationwhich gradually progresses to erythroderma with epidermalsloughing.13–21

overlooked. However, in particular cases its features are lym-phadenopathy, splenomegaly, and lymphocytosis. Sezary-like

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Table 1Erythroderma/exfoliative

dermatitis in the pediatric (1–14 years) age group: etiology

Cause(s)

1. Immunologic disorders

Disease(s)/syndrome(s)

? Omenn’s syndrome? Graft vs. host disease

? Cutaneous T-cell lymphoma? Hypogamma globulinemia? Di–George’s syndrome? Kwashiorkor? Renal failure

? Acrodermatitis enteropathica? Cystic ?brosis dermatitis? Leiner’s disease

? Amino acid disorders

? Staphylococcal scalded skin syndrome? Scarlet fever

? Neonatal candidosis? Toxic shock syndrome? Boric acid toxicity

? Drug-induced erythroderma/exfoliative dermatitis? Netherton’s syndrome

? Sjogren Larssen syndrome

? Keratitis–ichthyosis–deafness syndrome? Ectodermal dysplasias

? Neutral lipid storage disease with ichthyosis? Conradi–Hunermann syndrome? Trichothiodystrophy? Atopic dermatitis? Psoriasis vulgaris? Ichthyosis–HarlequinLamellarBullous

? Diffuse cutaneous mastocytosis? Toxic epidermal necrolysis? Pityriasis rubra pilaris? Seborrhoeic dermatitis? Norwegian Scabies

2. Metabolic/nutrition disorders

3. Infections

4. Toxicities/drug reactions

5. Part component of various syndrome(s)

6. Cutaneous disorders

notched cells can be identified in the peripheral blood smear.In contrast to Omenn’s syndrome, the IgG levels are elevated.Its histopathology is pathognomonic.13,22

is characterized by maculo-papular/eczematous lesions whichmay progress to cover the whole of the skin surface.

23,24 Insevere combined immuno-deficiency (SCID) the affectedchild often develops localized/widespread eczematous orseborrhoeic dermatitis.25

Acrodermatitis enteropathica

This condition is a well-recognized clinical entity in infantsand children. The initial lesions are vesiculobullous, crusted orpsoriasiform in mostly perioral and perianal locations. It is usu-ally accompanied by diarrhea, photophobia and irritability.26,27In addition to low serum zinc levels, serum alkaline phosphotaselevels are also reduced, as this enzyme is zinc dependent.13 Asimilar condition may be observed in children with AIDS.28Cystic fibrosis dermatitis

Initial presentation of this disease is quite different and ischaracterized by the development of severe rapidly progres-sive and unresponsive psoriasiform lesions. Pulmonary andgastrointestinal components complicate the condition later.The skin lesions may resolve following administration ofpancreatic enzymes and nutritional supplements.29,30

Leiner’s disease

This condition is comprised of a group of disorders with sim-ilar presentations characterized by erythroderma, diarrhoea,

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Kwashiorkor

This is a common form of routine malnutrition in both under-developed and developing countries. It may present withgeneralized erythema, edema and increased skin fragility.Excessive protein loss may result in renal and/or hepaticfailure in older children.13

© 2006 The International Society of Dermatology

EducationPediatric erythrodermaand failure to thrive. Ever since its first description severalinnovations have been made,20,31–34 including that by Gloveret al.,20 who proved that some of the affected individuals withLeiner’s phenotype may have an associated immuno-deficiency.20,35 Where the infant is apparently normal at birthand dermatitis and diarrhoea make an early appearance, thenthe latter is severe and chronic. The dermatitis is associatedwith progressive erythema and erosions which may ultim-ately become generalized. The condition does not respond totopical/oral medication. Adequate nutritional support alongwith hyper-alimentation and individualized treatment maybe helpful.13,33–36

Amino-acid disorders

Several reports have demonstrated the deficiency of variousamino-acids and their association with erythroderma.37–39Maple syrup urine disease is an interesting example. Its treat-ment includes restriction of essential amino-acids; otherwisethe severity of dermatitis worsens with increased control onamino-acid intake.40–42

Infections

Staphylococcal scalded skin syndrome (SSSS)

Unlike other erythrodermas in children SSSS onset is acute,accompanied by fever, systemic toxicity, and a positiveNikolsky’s sign. The erythema is generalized rapidly andprogresses to sloughing and erosions.13,43–46 Histopathologyof the lesion is imperative since it helps in distinguishing itfrom toxic epidermal necrolysis.13 Occasionally, widespreadstaphylococcal pustulation resembling generalized candido-sis may develop in a healthy child. However, culture is usuallypositive for staphylococcus. Accordingly, response to a rele-vant antibiotic is ensured.13,43

Scarlet fever

This condition forms an important differential diagnosis ofrubella, toxic shock syndrome, severe staphylococcal infec-tion, drug eruptions, mononucleosis and exanthem subitum.The erythroderma is transient and successfully resolvesfollowing institution of penicillin/erythromycin.

Congenital neonatal candidosis

The initial lesions are in the form of a maculopapular rash.Congenital candidosis gradually supervenes with the appear-ance of classical pustules, especially over the palms and soles.It spreads rapidly and often involves the umbilicus. The diag-nosis is easy: either through the demonstration of mycelia/conidia in 10% potassium hydroxide mount or on Gram’sstain followed by positive culture of candida Spp. Topical;sometimes systemic antifungals cause rapid resolution of thedisease,13,47 and in the neonatal form of generalized cutaneouscandidosis the lesions start in the oral cavity or napkins area.13

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Sehgal and Srivastava

Toxic shock syndrome

The clinical features of this condition include fever, hyperten-sion, and diffuse macular blanching erythroderma, followedby desquamation of the palms and soles. Dysfunction ofvarious organs or systems may be life-threatening. Surgicalwound infection of the skin, subcutaneous and/or soft tissueand also of bone may be predisposing factor(s).

Toxicity and drug reactions

Boric acid toxicity

Maculopapular lesions progressing to erythema, edema, anddesquamation are the salient clinical features of this conditionand Nikolsky’s sign may be positive. Other features includealopecia, vomiting, diarrhea, fever, and irritability.48 It is becauseof inadvertent absorption of boric acid powder from thenappy rash area, where boric acid is used as a dusting powder.Drug induced

Drug-induced erythrodermas in children are commonlyobserved with sulfanomide, isoniazid, streptomycin, non-steroidal anti-inflammatory drugs (NSAIDs), and antieplepticdrugs. However, cases have also been recorded withayurvedic, unani, homeopathic and indigenous medications.5Topical preparations have caused generalization of the exist-ing dermatoses in a proportion of cases. If the incriminatingdrug(s) are withdrawn and a symptomatic treatment insti-tuted, these cases have an excellent prognosis.

Various syndromes

Trichothiodystrophy (Tay’s syndrome)

The affected new born may have collodion membrane and beerythroderma with other features, including brittle, sparsehair, variable ichthyosis, and central nervous system manifes-tations. Erythroderma resolves itself during infancy.13,49Netherton’s syndrome

Infants and children affected with this disorder show a gener-alized exfoliative erythroderma. Trichorrhexis invaginata(bamboo hair) and atopy are its other features. The diseasemay be confused with generalized atopic dermatitis.50–52 Agenetic linkage has been established to SPINK-5 gene locus onchromosome 5q32 encoding the serum protease inhibitorLEKTI. This information may be useful in prenatal testing inany subsequent pregnancy of the mother of the affected child.53Sjogren Larssen syndrome

Coincident with erythroderma occurring during infancy, theaffected child has scaling, spasticity and mental retardation.The diagnosis is made either on the basis of enzyme assays onleukocytes, fibroblasts or skin biopsy, which may reveal adeficiency of enzyme fatty alcohol oxidoreductase.49

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Sehgal and SrivastavaKeratitis-ichthyosis-deafness (KID) syndrome

KID syndrome is a rare disorder where the infant usuallyhas diffusely thickened erythematous skin, which peelsoff in the course of the first week of life. Subsequently,atypical prominent follicular keratosis is identified over thehead and extremities. In the following years or decades,kerato-conjunctivitis with noticeable vascularization(pannus), along with neurosensory deafness,54 forms its partcomponent.

Ectodermal dysplasias

Erythroderma is rather an uncommon feature of the disease,and other pathognomonic features help in the diagnosis ofthis disorder.13

Neutral lipid storage disease with ichthyosis (Dorfman–Chanarin syndrome)

This condition resembles congenital ichthyosiform erythro-derma. Demonstration of lipid vacuoles in the skin and else-where in the body supports its diagnosis. It may also havefeatures such as cataract, myopathy, sensory-neural deafness,and growth retardation.13,55

Conradi-Hunermann syndrome

This condition affects infants and is characterized by thepresence of bands of ichthyosiform erythroderma alongBlaschko’s lines. The bands resolve in due course leavingbehind follicular atrophoderma. Radiography shows anasymptomatic, focal, encondral calcific strippling.13,56

sion of atopy. It is a pruritic, eczematous dermatosis, thesymptoms of which chronically fluctuate with remissions and

relapses. Most individuals with atopic dermatitis have anatopic diathesis identified through personal or family historyof asthma, allergic rhinitis and/or conjunctivitis and atopicdermatitis and/or predisposition to overproduction of immuno-globulin E (IgE) antibodies. Infants and children are most

commonly affected. Erythema, exudation, papules, vesiculo-papules, scales and crust are its salient acute lesions. It maytransform itself into erythroderma (Figs 3 and 4). Despitebeing widespread, the child is apparently well and thriving.Sparing of axillae and groins distinguishes it clinically fromseborrhoeic dermatitis in typical cases.13,57–59

per se is extremelyuncommon,60 which is also true in infancy. However, itsincidence is directly proportional to the increase in age.The clinical features of psoriasis are similar to those

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Pediatric erythrodermaEducation835

Figure 3Erythroderma/exfoliative dermatitis following atopic

dermatitis

observed in adults with psoriatic erythroderma.6,10,11 Theprognosis of the condition is poor in infants and youngchildren.11

nent may be responsible for erythroderma in infants and chil-dren. Harlequin fetus, bullous ichthyosis, lamellar ichthyosis,and congenital ichthyosiform erythroderma (CIE) are itsother clinical variants, of which to be cognizance. A Collo-dian membrane encasement is an essential part of both CIEand lamellar ichthyosis (Figs 5 and 6). However, in CIE it isreplaced by exfoliative erythroderma, whilst in lamellar ich-thyosis it is followed by generalized ichthyosis with plate-likescales. Infants with harlequin ichthyosis are born with gener-alized thick hyperkeratotic covering, which may prove fatalfollowing acute respiratory distress. Bullous (epidermolytichyper keratosis) ichthyosis initially may present with wide-spread areas of denuded skin. Gradually, blistering dimin-ishes and is replaced by ichthyosiform erythroderma withovert clinical features.61

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