Netherton Syndrome

Ibrahim Galadari, MD; Jameelah Al-Kaabi, MBBS; Hassan Galadari, MBBS


Skinmed. 2003;2(6) 

A 17-year-old Egyptian patient presented to the dermatology clinic of Al-Ain Hospital with a complaints of pruritic dry skin and short brittle hair since early infancy. The patient was born to healthy nonconsanguineous parents. He was a product of full-term normal pregnancy and delivery with a normal birth weight. At about age 4 weeks, he started to develop erythroderma and scaling. He had a history of recurrent infections, diarrhea, and failure to thrive in the first year of life. By age 2 years, the patient started to catch up with his weight and height. The erythroderma started to disappear slowly and erythematous, scaly, polycyclical, migratory lesions started to develop on his body. The patient achieved his developmental milestones with no delay and showed normal intelligence for his age. The family history was positive for eczema and allergic rhinitis in both his sister and brother. It was negative, however, for ichthyotic disorders. On physical examination, scaly, annular, migratory, and hyperkeratotic double-edged lesions were noticed on his back, chest, and abdomen (Figures 1 and 2). His hair was short, lacked luster, brittle, and beaded (Figure 3). His eyebrows and lashes were sparse and he had facial and perioral erythema with dryness of the affected area (Figure 3). Laboratory investigations showed normal blood workup, but with an elevation in IgE levels. Examination of hair under light microscopy showed bulging with ball-and-cup formation typical for trichorrhexis invaginata or bamboo hair (Figures 4 and 5). Skin biopsy showed mild hyperkeratosis, parakeratosis, reduced granular layer with accumulation of eosinophilic material, and mixed perivascular inflammatory cells infiltrate. A diagnosis of Netherton syndrome was made and the patient was started on antihistamines, emollients, and 10% urea.

Diffuse reddening of the face.

Annular keratoses surrounded by double margins of scales.

Polycyclic, brownish hyperkeratosis.

Bamboo hair.

Ball-and-cup hair shaft deformity.

Netherton syndrome (NS) is a rare autosomal recessive disorder. It is characterized by erythroderma, ichthyosis linearis circumflexa, atopic manifestations, and trichorrhexis invaginata or bamboo hair.[1,2,3,4,5] The gene involved in pathogenesis was assigned to chromosome 5q32 by linkage analysis and homozygosity mapping.[4,5,6,7] The region of NS harbors the SPINK5 gene. This gene encodes the serine protease inhibitor called lympho-epithelial kazal-type related inhibitor. Lympho-epithelial kazaltype related inhibitor is predominantly expressed in epithelial and lymphoid tissues. Eleven different mutations such as nonsense mutations, deletions, and insertions have been described in the SPINK5 gene.[4,5,6,7] Proteolysis is important in keratinocyte differentiation and epithelial formation. In affected persons, failure of cornification results from a defect in protolysis regulation.[4,6]

Patients with NS usually present with generalized erythroderma that is evident at or shortly after birth. Affected neonates are at risk to develop temperature instability, hypernatremic dehydration, failure to thrive, and recurrent infections. These life-threatening complications can result in a high postnatal mortality.[1,2,3,4,5,6,7,8] The erythroderma may persist into childhood or may disappear slowly in the second year of life.[1,2,3,4] By age 2 years, patients usually start to develop ichthyosis linearis circumflexa, which are gyrate, hyperkeratotic, serpiginous, migratory, annular, or polycyclic erythematous plaques with double-edged scales at the borders. This may be caused by a dermal influx of inflammatory cells that are phagocytosed and digested by keratinocytes resulting in disruption of keratinization.[1,2,3]

Atopic manifestations are present in most cases of NS. Patients may present with urticaria, asthma, atopic dermatitis, angioedema, hayfever, or high IgE levels in the serum and hypereosionophilia.[3,6,7,8] Most patients will even develop an allergy to foodstuffs, especially nuts.[1,2,3,6,7,8] Pruritus from atopic dermatitis may lead to scratching and lichenification, particularly at the antecubital fossae.[1,3,9]

Another important characteristic of NS is hair shaft defects. Patients' scalp hair is usually sparse, brittle, short, and lacks normal luster and shine. Examination by light microscopy will show hair nodes termed trichorrhexis invaginata or bamboo hair. This is a ball-and-cup hair shaft deformity that results from the invagination of the distal hair shaft (ball) into the expanded proximal hair shaft (cup). This invagination occurs at the site of an intermittent keratinizing defect of the hair cortex resulting from incomplete conversion of sulfhydryl group onto S-S disulfide bonds in the protein of the cortical fibers.[1,2,3,8,10]

The treatment of patients with NS is usually conservative and symptomatic. In the neonatal period, it is important to prevent temperature instability, the hypernatremic dehydration that may ensue, and to treat infections and other complications. Regular application of emollients and keratolytics and use of topical and systemic antibiotics, when indicated, are the mainstay of treatment.[1,2,3,9,10]

Topical steroids can be helpful but should be used with caution because they can lead to systemic toxicity because of the impaired skin barrier. Use of PUVA, narrow band UVB and retinoids are rarely, if ever, helpful. Oral retinoids have been reported to lead to deteri-oration.[1,11] Topical tacrolimus, found to be useful in treatment of atopic dermatitis, can lead to toxicity in patients with NS because of increased absorption due to skin barrier dys-function,[12] and should thus not be considered a mainstay of therapy.

In our case, the patient presented at age 17 years. The history of his complaints; the physical examinations that revealed gyrate lesions with double-edged scaling; and the brittle, short hair increased the possibility of NS as part of our differential diagnosis. Only after further investigations that showed bamboo hair by light microscopy was a diagnosis of NS made. The patient was started on conservative and symptomatic treatment with 10% urea, emollients, and antihistamines. At 1-year follow-up the patient has shown a positive response with intermittent exacerbations of his condition.


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