Netherton Syndrome – Responding to Oral Retinoids

Dear Editor, Netherton syndrome (NS) is a rare autosomal recessive ichthyotic disorder characterized by the triad of ichthyosis linearis circumflexa (ILC), atopic diathesis, and hair shaft abnormalities.[1] ILC was first described by Comel in 1949 as polycyclic erythematous plaques with double-edged migratory scaling.[2] In 1958, Earl Netherton identified trichorrhexis invaginata, a pathognomonic hair shaft defect.[3] Wilkinson later added atopic diathesis complete the triad in 1964.[2] A 7-year-old boy from consanguineous parents presented with itchy raised lesions and scaling for 10 days. He had been diagnosed with psoriasis vulgaris and treated with methotrexate, which was ineffective. His medical history indicated that he had similar episodes at 8 months of age. He had similar complaints on and off with periods of waxing and waning. There were no joint pain or nail changes and no family history of similar conditions. The child experienced recurrent respiratory infections and had a personal and family history of atopy. Examination revealed well-defined erythematous polycyclic plaques with double-edged scales [Figure 1a and b] and short and brittle hair. The palms, soles, nails, oral cavity, and genitalia were normal. Microscopic examination of the scalp hairs revealed pili torti [Figure 1c]. Serum immunoglobulin E (IgE) levels were elevated (2058 IU/ml), and eosinophil count was 12% (normal range: 1-6). Histopathology showed parakeratosis, spongiosis, and lymphocytic infiltrates suggestive of an ichthyosiform disorder [Figure 1d]. Genetic testing for confirmation was suggested, but parents refused due to cost. The patient was treated with topical emollients, antihistamines, and oral Acitretin (0.5 mg/kg/day) and showed complete resolution after 2 months [Figure 2a and b]. He is currently on monthly follow-up.Figure 1: (a and b) Shows erythematous plaques with double edged scales over trunk and extremities. (c) Microscopic image showing Pili torti. (d) (H and E, ×10) shows parakeratosis, spongiosis, lymphocytic infiltrates in epidermis and dermisFigure 2: (a and b) Shows complete resolution of lesions after treatment with oral acitretin at 2 month follow upDISCUSSION NS is a rare genodermatosis occurring in approximately 1 in 200,000 live births.[1] It results from a loss-of-function mutation in the SPINK5 gene on chromosome 5q31-32, which encodes the serine protease inhibitor lymphoepithelial kazal-type-related inhibitor.[4] ILC manifests as serpiginous, polycyclic, and erythematous plaques with double-edged scales, typically appearing after 2–3 years of age. Trichorrhexis invaginata is pathognomonic of NS and affects 20%–50% of hair shafts.[1] Associated hair shaft defects include golf tee hair, matchstick sign, pili torti, and trichorrhexis nodosa.[1] Atopic diathesis can present as atopic dermatitis, angioedema, urticaria, and elevated serum IgE levels. In the context of ILC, hair shaft abnormalities, atopic dermatitis, and elevated IgE and eosinophils, NS diagnosis is supported. Histopathology may resemble psoriasiform dermatitis, as seen in our case, which exhibited features suggestive of ichthyosiform disorder. Genetic confirmation through SPINK5 mutation testing can solidify the diagnosis. Differential diagnoses include congenital ichthyosis, erythrodermic psoriasis, seborrheic dermatitis, and staphylococcal scalded skin syndrome, hyper-IgE syndrome, all ruled out in this case. Topical emollients are the first-line treatment.[1] It is supplemented by topical corticosteroids and calcineurin inhibitors. Systemic options include IV immunoglobulins, biological agents, and retinoids. Nevet et al. reported significant improvement with oral Acitretin (1 mg/kg) and topical moisturizers.[5] CONCLUSION NS is an infrequent disorder. This case is reported to emphasize the importance of considering the possibility of NS when an atopic child is brought with features like ILC and hair shaft abnormality. 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.