Differential Diagnosis of Neonatal and Infantile Erythroderma

View metadata, citation and similar papers at core.ac.uk brought to you by CORE Acta Dermatovenerol Croat 2007;15(3):178-190 REVIEW Differential Diagnosis of Neonatal and Infantile Erythroderma Lena Kotrulja1, Slobodna Murat-Sušić2, Karmela Husar2 1University Department of Dermatology and Venereology, Sestre milosrdnice University Hospital; 2University Department of Dermatology and Venereology, Zagreb University Hospital Center and School of Medicine, Zagreb, Croatia Corresponding author: SUMMARY Neonatal and infantile erythroderma is a diagnostic and Lena Kotrulja, MD, MS therapeutic challenge. Numerous underlying causes have been reported. Etiologic diagnosis of erythroderma is frequently difficult to University Department of Dermatology establish, and is usually delayed, due to the poor specificity of clinical and Venereology and histopathologic signs. Differential diagnosis of erythroderma is Sestre milosrdnice University Hospital a multi-step procedure that involves clinical assessment, knowledge of any relevant family history and certain laboratory investigations. Vinogradska 29 Immunodeficiency must be inspected in cases of severe erythroderma HR-10000 Zagreb with alopecia, failure to thrive, infectious complications, or evocative Croatia histologic findings. The prognosis is poor with a high mortality rate [email protected] in immunodeficiency disorders and severe chronic diseases such as Netherton’s syndrome. Received: June 14, 2007 KEY WORDS: erythroderma, neonatal, infantile, generalized Accepted: July 11, 2007 exfoliative dermatitis INTRODUCTION Erythroderma is defined as an inflammatory Neonatal and infantile erythroderma is a diag- skin disorder affecting total or near total body sur- nostic and therapeutic challenge. Erythrodermic face with erythema and/or moderate to extensive neonates and infants are frequently misdiagnosed scaling (1). It is a reaction pattern of the skin that with eczema and inappropriate topical steroid can complicate many underlying skin conditions at treatment can lead to Cushing syndrome. Delay any age. In neonatal period it can be the primary in the establishment of the correct diagnosis can manifestation of numerous conditions (2). How- be fatal. Differential diagnosis of erythroderma is a ever, some disorders in infants may initially be lo- multi-step procedure that involves clinical assess- calized and then eventually develop into extensive ment, knowledge of any relevant family history, erythroderma (1). Differential diagnosis includes and certain laboratory investigations (2). benign transient, inflammatory, infectious, metabolic and immune diseases, many of which have a hereditary basis. Some of these diseases are Laboratory investigations potentially life threatening, and erythroderma itself Differential diagnosis of erythroderma can can cause serious medical complications such as be facilitated by some laboratory tests (Table 1). electrolyte imbalance, hypoproteinemia, dehydra- Serum IgE levels are profoundly increased in tion, sepsis, and temperature instability (3). Netherton’s and Omenn’s syndromes, and mild- 178 Kotrulja et al. Acta Dermatovenerol Croat Neonatal and infantile erythroderma 2007;15(3): Kotrulja et al. Acta Dermatovenerol Croat Neonatal and infantile erythroderma 2007;15(3):178-190 and other ichthyoses. Fibroblast culture from bi- Table 1. Laboratory investigations in neonatal and opsy can help reach definitive diagnosis of several infantile erythroderma metabolic diseases (3). Non-bullous and bullous 1. Potassium hydroxide (KOH) stain for demon- ichthyosiform erythroderma are distinguishable stration of mycelia/spores and fungal culture on histology (4). In the graft-versus-host reaction, 2. Gram’s stain for bacteria and bacterial culture histology is valuable in severe cases, but in milder 3. Tzanck test cases only some of the findings may be present and the diagnosis can easily be missed. In blister- 4. Demonstration of Sarcoptes scabiei ing diseases, it is helpful to take biopsy from the 5. Microscopic analysis of hair shaft abnormali- border of the blister, including its roof, to facilitate ties assessment of the level of cleavage (2). 6. Complete hemogram It is helpful to divide the subject of neonatal 7. Skin biopsy for microscopic pathology erythroderma into several categories, roughly ac- 8. Serum zinc and alkaline phosphatase levels cording to pathogenesis (Table 2). 9. Sweat chloride levels 10. Lipid profile including essential fatty acid lev- Table 2. Causes of neonatal and infantile eryth- els roderma 11. Evaluation of humoral and cellular immunity; Transient neonatal dermatoses IgA, IgG, IgM, IgE, complement component, T Erythema toxicum neonatorum and B lymphocytes Miliaria 12. Biotinidase/holocarboxylase synthetase levels Cutaneous disorders 13. Plasma amino acid levels and urine organic Atopic dermatitis acids Infantile seborrheic dermatitis Psoriasis ly increased in early atopic eczema. Appropriate Diffuse cutaneous mastocytosis smears for potassium hydroxide (KOH) stain, Gram stain, Tzanck test as well as cultures for Ichthyosis fungal, bacterial, or viral diseases should be per- Netherton’s syndrome formed if infection is suspected. Chest radiograph Infections may be useful to evaluate thymic shadow, which Staphylococcal scalded skin syndrome (SSSS) may be absent in neonates with severe combined immunodeficiency (SCID) (3). Serum electrolyte Congenital and neonatal candidiasis and albumin concentrations should be measured Congenital herpes simplex infection because children with erythroderma are at a risk Syphilis of hypernatremic dehydration as well as enteral Toxic and drug reactions and transcutaneous protein losses. Complete Toxic epidermal necrolysis blood count should be supplemented by more de- tailed immunologic studies if Omenn’s syndrome Drug reactions or graft-versus-host disease is suspected (2). Metabolic disorders Serum amino and urine organic acids should be Acrodermatitis enteropathica determined if primary metabolic diseases such as Cystic fibrosis aminoaciduria or biotin deficiency are suspected. Biotinidase level can be obtained if biotin deficien- Essential fatty acid deficiency cy is suspected (3). Amino acid disorders Disorders of biotin metabolism HISTOLOGY Immune disorders As it is very important to establish the diag- Graft versus host disease (GVHD) nosis rapidly, it is advisable to take two or three Severe combined immunodeficiency (SCID) simultaneous skin biopsies from different sites. Omenn’s syndrome Histology and immunohistochemistry can dif- ferentiate Omenn’s from Netherton’s syndrome Hypogammaglobulinemia ACTA DERMATOVENEROLOGICA CROATICA 179 Kotrulja et al. Acta Dermatovenerol Croat Neonatal and infantile erythroderma 2007;15(3):178-190 TRANSIENT NEONATAL DERMATOSES Erythema toxicum neonatorum (ETN) is the most common transient benign rash in healthy neonates. The incidence is controversial, and ranges from 30% to 70% in various surveys. The cause of ETN has not yet been established (5). The pres- ence of ETN correlates well with birth weight and gestational age. It is virtually never seen in pre- mature infants or those weighing less than 2500 g (6). Congenital lesions may occur, but the majority of cases have the onset between 24 and 48 hours of life. Lesions wax and wane, usually lasting for Figure 2. Atopic dermatitis, a more extensive dis- a week or less, but cases lasting beyond 2 weeks tribution with pronounced pruritus. of life have been reported. It is characterized by or pustules with surrounding erythema forming small erythematous macules with or without cen- erythematous plaques can occur and be more dif- tral papule or pustule, measuring 1 to 3 mm in di- ficult to diagnose (Fig. 1b). Peripheral eosinophilia ameter, which may appear first on the face and has also been associated in about 15% of cases spread to the trunk and proximal extremities, but (6). Skin biopsy is rarely needed. The diagnosis of may appear anywhere on the body except for the ETN can usually be made by clinical appearance palms and soles (Fig. 1a) (5,6). Although the char- alone, but scraping of the pustule will reveal eosin- acteristic lesions of ETN are usually discrete and ophils with a few scattered neutrophils. No therapy scattered, extensive cases with confluent papules, is needed, for ETN resolves spontaneously (5,6). MILIARIA The term miliaria is used to describe a group of transient eccrine disorders. Miliaria is common in summer months and is also noted in infants housed in incubators (5). There are three forms of miliaria due to occlusion of sweat ducts at various levels, resulting in leakage of sweat in the epi- dermis or papillary dermis. Only miliaria rubra can progress to erythroderma, mostly in hot and humid conditions (5,6). Miliaria rubra occurs between the 11th and 15th day of life and it usually affects sites of friction or occlusion such as the neck and face, but also occurs on the trunk. Lesions are erythem- Figure 1. (a) Erythema and pustules in erythema atous, non-follicular papules or papulovesicles of toxicum neonatorum; (b) erythema toxicum neo- 1-3 mm in size (6). natorum with numerous pustules. CUTANEOUS DISORDERS Atopic dermatitis Atopic dermatitis (AD) presents within the first 6 months of life in 60% of children. Severe generalized AD is unusual in neonates, but because AD is such a common problem, it is the most common cause of acquired or non-congenital erythroderma in infants (Fig. 2) (3). From the clinical point of view, in the first months of life AD is characterized

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