Indian Journal of Paediatric Dermatology

REVIEW ARTICLE
Year
: 2020  |  Volume : 21  |  Issue : 1  |  Page : 15--21

Neonatal and infantile erythroderma revisited


Bhavya Swarnkar1, Rashmi Sarkar2,  
1 Department of Dermatology, AIIMS, New Delhi, India
2 Department of Dermatology, Maulana Azad Medical College, New Delhi, India

Correspondence Address:
Dr Rashmi Sarkar
Department of Dermatology, Maulana Azad Medical College, New Delhi - 110 002
India

Abstract

Erythroderma is the term applied to any inflammatory skin disease affecting more than 90% of the body surface. The incidence of neonatal and infantile erythroderma was 0.11% in an Indian study. There are various causes of neonatal and infantile erythroderma such as congenital, metabolic, papulosquamous, eczematous, drug induced, infections, autoimmune diseases, and malignancy but it is quite difficult to establish the etiology in early stage of life due to less specific clinical, biochemical and histological findings as compared to adults. Proper history, examination, skin biopsy, and various other relevant investigations (based on the differential diagnoses) are imperative to the diagnosis of neonatal and infantile erythroderma. Ruling out immunodeficiency in a child with failure to thrive is important. Since erythroderma is a dermatological emergency, its wise management is mandatory. Vitals, input-output, serum electrolytes, etc., are to be precisely monitored. Barrier nursing is of utmost importance in such cases. Any complication is to be dealt with, and specific treatment of particular cause of childhood and infantile erythroderma is to be done.



How to cite this article:
Swarnkar B, Sarkar R. Neonatal and infantile erythroderma revisited.Indian J Paediatr Dermatol 2020;21:15-21


How to cite this URL:
Swarnkar B, Sarkar R. Neonatal and infantile erythroderma revisited. Indian J Paediatr Dermatol [serial online] 2020 [cited 2020 Jan 25 ];21:15-21
Available from: http://www.ijpd.in/text.asp?2020/21/1/15/273846


Full Text



 Introduction



Erythroderma or exfoliative dermatitis is the term applied to any inflammatory skin disease affecting more than 90% of the body surface.[1] It is a reaction pattern of the skin manifested by erythema and scaling that can complicate many underlying skin conditions at any age. It is a less common entity in the pediatric patients.[2]

The incidence of neonatal and infantile erythroderma was 0.11% in a study done by Sarkar et al. in Delhi.[3]

In adults, erythroderma may be due to drugs or secondary to preexisting dermatoses, while in the neonatal period it can be the primary manifestation of several conditions such as immunodeficiency and ichthyosiform syndrome.[4] The etiology of neonatal and infantile erythroderma is difficult to find and is often delayed due to the less specific clinical, biochemical and histological signs. Moreover, the causes of erythoderma in this age group are quite distinctive.[5]

It is imperative for dermatologists as well as pediatricians to recognize erythroderma, its consequences and differentiate it from benign erythemas of childhood, and to prevent its mismanagement.

 Classification



It can be classified based on the following:

Duration of disease

Acute (few days)Chronic.

Age of onset [6]

Congenital

IchthyosisPrimary immunodeficiency syndrome (PIDS).

Neonatal (<1 month)

IchthyosisPIDSPsoriasisMetabolic disease.

Infantile (>1 month–1 year)

PIDSSeborrhoeic dermatitisPapulosquamous disorders- psoriasis, pityriasis rubra pilaris (PRP)Atopic dermatitisIchthyosisDrug-inducedMetabolic/nutritionalCutaneous T-cell lymphomaRarely - Kawasaki disease, dermatomyositis, sarcoidosis, pemphigus foliaceus.

Vesicles/bullae formation [6]

Bullous erythroderma

Staphylococcal scalded skin syndrome (SSSS)Bullous ichthyosisDiffuse cutaneous mastocytosis.

Scaling and exfoliative erythroderma

Keratinization disordersImmune deficienciesMetabolic diseases.

Etiology [4],[5],[7],[8],[9],[10],[11]

Ichthyosis

nonbullous ichthyosiform erythroderma (NBIE)Bullous ichthyosiform erythroderma (BIE)Netherton's syndromeConradi–Hunermann syndrome (CHS)Sjogren–Larsson syndrome (SLS)ErythrokeratodermaLamellar ichthyosis [Figure 1]Trichothiodystrophy (TTD)Keratitis Ichthyosis Deafness (KID) syndromeNeutral lipid storage disease with ichthyosis.

Transient neonatal dermatoses

MiliariaErythema toxicum neonatorum.

Infections

SSSSScarlet feverNeonatal candidiasisToxic shock syndrome (TSS)Congenital herpes simplex virus (HSV) infectionSyphilis.

Infestations

Norwegian scabies.

Immunodeficiency

Omenn's syndromeSevere combined immunodeficiency syndrome (SCID)Graft versus host diseaseWiskott–Aldrich syndromeDi Georges syndrome.

Drug-induced

Boric acid toxicityCeftriaxoneAmpicillin, amoxicillinVancomycinAntiepilepticsSulfonamidesTopical tarThioacetazoneCaptoprilCimetidineAntitubercular drugsHomeopathic and indigenous drugs.

Metabolic/nutritional

Disorders of biotin metabolismMultiple carboxylase deficiencyEssential fatty acid deficiencyUrea cycle disorders (argininosuccinic aciduria, citrullinaemia)Renal failureKwashiorkorAcrodermatitis enteropathicaCystic fibrosisLeiner's disease.

Eczematous disorders

Infantile seborrheic dermatitis [Figure 2] and [Figure 3]Atopic dermatitis.

Papulosquamous disorders

PsoriasisPRP.

Malignancies

Diffuse cutaneous mastocytosisCutaneous T-cell lymphoma.

Autoimmune

DermatomyositisKawasaki diseaseSarcoidosisPemphigus foliaceus.

Ectodermal dysplasiasIdiopathic.{Figure 1}{Figure 2}{Figure 3}

 Etiology



In a retrospective study done in France by Pruszkowski et al., on 51 cases of erythroderma in neonates and infants, excluding those with blistering, the various underlying causes were: immunodeficiency - 30%, ichthyosis (simple and complex) - 24%, Netherton syndrome - 18%, eczematous and papulosquamous dermatitis - 20%, and erythroderma of unknown etiology-10%[12] [Table 1] shows causes of childhood erythroderma in studies done in India.{Table 1}

 Pathogenesis



The pathogenesis of erythroderma appears complex. It develops secondary to an intricate interaction of cytokines and cellular adhesion molecules like interleukin 1, 2, intercellular adhesion molecule, and the tumor necrosis factor (TNF). These interactions result in a florid increase in the epidermal cell turnover rate and accelerated mitosis resulting in excessive scaling and erythema.[15],[16],[17],[18] It manifests as a excessive loss of epidermal material along with protein, iron, and folate.[17] In addition to these basic changes, all above mentioned diseases have their own specific pathogenesis.

 Approach



1. History [4],[5],[7],[8],[9],[10],[11],[19]

Family history-BIE, psoriasis, PRP, Omenn's syndrome, Netherton's syndrome, atopyHistory of consanguinity-Ichthyosis, Netherton syndrome, primary immunodeficiency disorderCongenital onset-ichthyosis, infections, immunodeficiency disordersRecurrent infection and diarrhea-immunodeficiency disordersNeurological complaints (Ichthyosiform syndromes, biotinase deficiency)Blood transfusion-GVHRPreceding purulent infection-SSSSConcomitant infection in mother-TSS, congenital cutaneous candidiasis (CCC)Failure to thrive - Netherton syndrome, immunodeficiency diseases, metabolic disordersDiarrhea - GVHR, Netherton syndrome, Omenn syndromePeriorificial dermatitis-metabolic and nutritional disordersBlisters-SSSS, mastocytosis, BIECollodion baby - NBIE and other ichthyosisFever-SSSS, GVHR, TSSAtopy-Netherton syndrome, atopic dermatitisPresence of linear epidermal nevus in family members - BIEH/O unexplained death in previous children - Omenn's syndrome.

2. Examination [4],[5],[7],[8],[9],[10],[11],[19]

General

Shock-TSS, toxic epidermal necrolysis (TEN)Lymphadenopathy – Omenn's syndrome, GVHR, atopic dermatitisHepatosplenomegaly-Omenn's syndrome, GVHR.

Systemic

Ophthalmological-cataract - CHS, neutral lipid storage disease, fundus-glistening dots-SLSAuditory-KID syndrome, neutral lipid storage diseaseRespiratory - cystic fibrosisCNS-TTD (spasticity, mental retardation).

Mucocutaneous

Type of scales (ichthyosiform or fine scales)Spared areas - PRPThe presence of specific lesion (keratotic follicular papules-PRP, well-defined erythematous scaly plaques-psoriasis, bulla, and erosions)

Skin induration-immunodeficiency, atopic dermatitis, neuroichthyosis, generalized cutaneous mastocytosisDarier's sign-mastocytosisPositive Nikolsky's sign-SSSS, boric acid toxicitySkin tenderness - SSSS, TEN, TSSDistribution (flexor or extensor)Sparing of napkin area and axillae - Atopic dermatitisNail changes-paronychia and dystrophy in CCCAlopecia-Omenn's syndrome, GVHR, Netherton's syndrome, Biotin metabolism disorders, citrullinemia, trichothiodystrophy (brittle hair)Hair dysplasia - Netherton syndrome (bamboo hair-trichorrhexis invaginata, nodosa)Mucosal examinationPalmoplanter thickening - PRPSwirled pattern of erythroderma - CHSEctrodactyly, cleft lip-ectodermal dysplasia.

3. Investigations [4],[5],[7],[8],[9],[10],[11],[19]

Skin biopsy - It is essential, and as in adults, it is advisable to take 2–3 specimens simultaneously from different sites.

Findings are mentioned in [Flow Chart 1].

Swabs from skin, eyes, nose, and umbilicus – SSSS, TSS, CCCCulture of urine, blood, and CSF - candidiasisKOH mount - candidiasisTzanck smear - Pemphigus foliaceus, HSV infectionWet mount - Sarcoptes miteDermatoscopy - Netherton syndromeHair microscopy - Netherton syndrome (bamboo hair), Trichothyodystrophy (alternate dark and light bands-tiger skin pattern)High vaginal swab from mother -Staphylococcus aureus or CCC.Complete blood count - Anemia-Cystic fibrosis, malnutrition

Leukocytosis - SSSS, TSSEosinophil count – It is markedly increased in Omenn syndrome and Netherton syndrome. Mildly increased in atopic dermatitisThrombocytopenia - Wiskott Aldrich syndrome.

Serum IgE and other immunoglobulins – Omenn syndrome, Netherton's syndrome, atopic dermatitisComplement level - Leiner's diseaseT and B lymphocytes count - Immunodeficiency syndromesZinc and alkaline phosphate levels - Acrodermatitis enteropathicaAssays of essential fatty acids, amino acids, holocarboxylase and biotinidase-to rule out metabolic disordersSweat chloride levels-cystic fibrosisHolocarboxylase synthetase activity in leukocytes and fibroblasts-hydroxysteroid dehydrogenaseBlood for fatty acid levels-essential fatty acid deficiencyGenetic analysis for SPINK5 - Netherton syndromeX-ray long bones - CHNX-ray chest-absent thymic shadow - SCIDHistamine and its metabolite levels, tryptase in serum or urine-mastocytosisSerum electrolytes-hypernatremic dehydrationSerum albuminHLA B17-positive in congenital psoriasisChromatography-blood and urine-carboxylase deficiency and urea cycle disordersAudiometry - KID syndromeCapillary blood gas analysis-ketoacidosis (holocarboxylase synthetase deficiency) [Flow Chart 2].[INLINE:1][INLINE:2]

 Treatment



General measures

Temperature, pulse, respiratory rate, blood pressure, and input-output need to be strictly monitored. Electrolyte, metabolic acidosis is to be looked for and managed carefully. Adequate application of bland emollients, wet dressings are helpful in decreasing scaling and fissuring. 0.01% potassium permanganate soaks are used over erosions for its astringent, antibacterial, and antifungal effects. Severe complications such as septicemic infections, hypoalbuminemia, hyperpyrexia, hypernatremic dehydration, and cardiac failure should be managed timely.[4],[5],[7],[8],[9],[10],[11],[19]

Specific measures

Treatment of underlying diseases such as antibiotics, antifungals, and antiscabicidal for bacterial infections, candidiasis, and scabies, respectively. Atopic dermatitis and drug-induced erythroderma may need a short course of oral corticosteroids. Drug-induced cases also require withdrawal of offending drug. Psoriasis, ichthyosis may need oral retinoids while immunosuppressants are required for the management of dermatomyositis, pemphigus foliaceus, and sarcoidosis. Immunodeficiencies are treated with bone marrow transplantation.[4],[5],[7],[8],[9],[10],[11],[19]

 Recent Advances



Oral liarozole, a retinoic acid metabolism-blocking agent, an alternative to systemic retinoid therapy, can be given in patients with lamellar ichthyosis [20]Water-in-oil emulsion of 10% N-acetyl cysteine in combination with 5% urea topically for lamellar ichthyosis, epidermolytic ichthyosis which can present as erythroderma [21],[22]Being relatively new, the experience of biologics in children is very less. Recommendations of Italian expert group for the treatment of severe psoriasis including erythrodermic psoriasis exist. This group has recommended adalimumab as a 1st-line treatment option for severe psoriasis in children >4 years of age, and etanercept and ustekinumab as the 2nd-line treatment modalities for children >6 years and >12 years of age, respectively.[23]

 Conclusion



Neonatal erythroderma is a potentially life-threatening condition and its clinical care and prognosis are related to its underlying causes. Many a times, it is difficult to reach an aetiological diagnosis on the basis of clinical information alone and additional measures, especially skin biopsy, may be very helpful. There is a need of multidisciplinary approach for the management of such patients by dermatologists and pediatricians.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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