Generic selectors
Exact matches only
Search in title
Search in content
Post Type Selectors
Search in posts
Search in pages
Filter by Categories
15th National Conference of the IAOMFP, Chennai, 2006
Abstract
Abstracts from current literature
Acne in India: Guidelines for management - IAA Consensus Document
Addendum
Announcement
Art & Psychiatry
Article
Articles
Association Activities
Association Notes
Award Article
Book Review
Brief Report
Case Analysis
Case Letter
Case Letters
Case Notes
Case Report
Case Reports
Clinical and Laboratory Investigations
Clinical Article
Clinical Studies
Clinical Study
Commentary
Conference Oration
Conference Summary
Continuing Medical Education
Correspondence
Corrigendum
Cosmetic Dermatology
Cosmetology
Current Best Evidence
Current Issue
Current View
Derma Quest
Dermato Surgery
Dermatopathology
Dermatosurgery Specials
Dispensing Pearl
Do you know?
Drug Dialogues
e-IJDVL
Editor Speaks
Editorial
Editorial Remarks
Editorial Report
Editorial Report - 2007
Editorial report for 2004-2005
Errata
Erratum
Focus
Fourth All India Conference Programme
From Our Book Shelf
From the Desk of Chief Editor
General
Get Set for Net
Get set for the net
Guest Article
Guest Editorial
History
How I Manage?
IADVL Announcement
IADVL Announcements
IJDVL Awards
IJDVL AWARDS 2015
IJDVL Awards 2018
IJDVL Awards 2019
IJDVL Awards 2020
IJDVL International Awards 2018
Images in Clinical Practice
In Memorium
Inaugural Address
Index
Knowledge From World Contemporaries
Leprosy Section
Letter in Response to Previous Publication
Letter to Editor
Letter to the Editor
Letter to the Editor - Case Letter
Letter to the Editor - Letter in Response to Published Article
LETTER TO THE EDITOR - LETTERS IN RESPONSE TO PUBLISHED ARTICLES
Letter to the Editor - Observation Letter
Letter to the Editor - Study Letter
Letter to the Editor - Therapy Letter
Letter to the Editor: Articles in Response to Previously Published Articles
Letters in Response to Previous Publication
Letters to the Editor
Letters to the Editor - Letter in Response to Previously Published Articles
Letters to the Editor: Case Letters
Letters to the Editor: Letters in Response to Previously Published Articles
Medicolegal Window
Messages
Miscellaneous Letter
Musings
Net Case
Net case report
Net Image
Net Images
Net Letter
Net Quiz
Net Study
New Preparations
News
News & Views
Obituary
Observation Letter
Observation Letters
Oration
Original Article
ORIGINAL CONTRIBUTION
Original Contributions
Pattern of Skin Diseases
Pearls
Pediatric Dermatology
Pediatric Rounds
Perspective
Presedential Address
Presidential Address
Presidents Remarks
Quiz
Recommendations
Regret
Report
Report of chief editor
Report of Hon : Treasurer IADVL
Report of Hon. General Secretary IADVL
Research Methdology
Research Methodology
Resident page
Resident's Page
Resident’s Page
Residents' Corner
Residents' Corner
Residents' Page
Retraction
Review
Review Article
Review Articles
Reviewers 2022
Revision Corner
Self Assessment Programme
SEMINAR
Seminar: Chronic Arsenicosis in India
Seminar: HIV Infection
Short Communication
Short Communications
Short Report
Snippets
Special Article
Specialty Interface
Studies
Study Letter
Study Letters
Supplement-Photoprotection
Supplement-Psoriasis
Symposium - Contact Dermatitis
Symposium - Lasers
Symposium - Pediatric Dermatoses
Symposium - Psoriasis
Symposium - Vesicobullous Disorders
SYMPOSIUM - VITILIGO
Symposium Aesthetic Surgery
Symposium Dermatopathology
Symposium-Hair Disorders
Symposium-Nails Part I
Symposium-Nails-Part II
Systematic Review and Meta-Analysis
Systematic Reviews and Meta-analyses
Systematic Reviews and Meta-analysis
Tables
Technology
Therapeutic Guideline-IADVL
Therapeutic Guidelines
Therapeutic Guidelines - IADVL
Therapeutics
Therapy
Therapy Letter
Therapy Letters
View Point
Viewpoint
What’s new in Dermatology
Generic selectors
Exact matches only
Search in title
Search in content
Post Type Selectors
Search in posts
Search in pages
Filter by Categories
15th National Conference of the IAOMFP, Chennai, 2006
Abstract
Abstracts from current literature
Acne in India: Guidelines for management - IAA Consensus Document
Addendum
Announcement
Art & Psychiatry
Article
Articles
Association Activities
Association Notes
Award Article
Book Review
Brief Report
Case Analysis
Case Letter
Case Letters
Case Notes
Case Report
Case Reports
Clinical and Laboratory Investigations
Clinical Article
Clinical Studies
Clinical Study
Commentary
Conference Oration
Conference Summary
Continuing Medical Education
Correspondence
Corrigendum
Cosmetic Dermatology
Cosmetology
Current Best Evidence
Current Issue
Current View
Derma Quest
Dermato Surgery
Dermatopathology
Dermatosurgery Specials
Dispensing Pearl
Do you know?
Drug Dialogues
e-IJDVL
Editor Speaks
Editorial
Editorial Remarks
Editorial Report
Editorial Report - 2007
Editorial report for 2004-2005
Errata
Erratum
Focus
Fourth All India Conference Programme
From Our Book Shelf
From the Desk of Chief Editor
General
Get Set for Net
Get set for the net
Guest Article
Guest Editorial
History
How I Manage?
IADVL Announcement
IADVL Announcements
IJDVL Awards
IJDVL AWARDS 2015
IJDVL Awards 2018
IJDVL Awards 2019
IJDVL Awards 2020
IJDVL International Awards 2018
Images in Clinical Practice
In Memorium
Inaugural Address
Index
Knowledge From World Contemporaries
Leprosy Section
Letter in Response to Previous Publication
Letter to Editor
Letter to the Editor
Letter to the Editor - Case Letter
Letter to the Editor - Letter in Response to Published Article
LETTER TO THE EDITOR - LETTERS IN RESPONSE TO PUBLISHED ARTICLES
Letter to the Editor - Observation Letter
Letter to the Editor - Study Letter
Letter to the Editor - Therapy Letter
Letter to the Editor: Articles in Response to Previously Published Articles
Letters in Response to Previous Publication
Letters to the Editor
Letters to the Editor - Letter in Response to Previously Published Articles
Letters to the Editor: Case Letters
Letters to the Editor: Letters in Response to Previously Published Articles
Medicolegal Window
Messages
Miscellaneous Letter
Musings
Net Case
Net case report
Net Image
Net Images
Net Letter
Net Quiz
Net Study
New Preparations
News
News & Views
Obituary
Observation Letter
Observation Letters
Oration
Original Article
ORIGINAL CONTRIBUTION
Original Contributions
Pattern of Skin Diseases
Pearls
Pediatric Dermatology
Pediatric Rounds
Perspective
Presedential Address
Presidential Address
Presidents Remarks
Quiz
Recommendations
Regret
Report
Report of chief editor
Report of Hon : Treasurer IADVL
Report of Hon. General Secretary IADVL
Research Methdology
Research Methodology
Resident page
Resident's Page
Resident’s Page
Residents' Corner
Residents' Corner
Residents' Page
Retraction
Review
Review Article
Review Articles
Reviewers 2022
Revision Corner
Self Assessment Programme
SEMINAR
Seminar: Chronic Arsenicosis in India
Seminar: HIV Infection
Short Communication
Short Communications
Short Report
Snippets
Special Article
Specialty Interface
Studies
Study Letter
Study Letters
Supplement-Photoprotection
Supplement-Psoriasis
Symposium - Contact Dermatitis
Symposium - Lasers
Symposium - Pediatric Dermatoses
Symposium - Psoriasis
Symposium - Vesicobullous Disorders
SYMPOSIUM - VITILIGO
Symposium Aesthetic Surgery
Symposium Dermatopathology
Symposium-Hair Disorders
Symposium-Nails Part I
Symposium-Nails-Part II
Systematic Review and Meta-Analysis
Systematic Reviews and Meta-analyses
Systematic Reviews and Meta-analysis
Tables
Technology
Therapeutic Guideline-IADVL
Therapeutic Guidelines
Therapeutic Guidelines - IADVL
Therapeutics
Therapy
Therapy Letter
Therapy Letters
View Point
Viewpoint
What’s new in Dermatology
View/Download PDF

Translate this page into:

Therapy Letter
89 (
5
); 754-756
doi:
10.25259/IJDVL_558_2022
pmid:
37317770

Intravenous immunoglobulin for the management of Netherton syndrome

Department of Dermatology, AFMC, Pune, Maharashtra, India
Department of Pediatrics, AFMC, Pune, Maharashtra, India
Corresponding author: Dr. Shekhar Neema, Department of Dermatology, AFMC, Pune, Maharashtra, India. shekharadvait@gmail.com
Licence
This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, transform, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

How to cite this article: Neema S, Vasudevan B, Rathod A, Mukherjee S, Vendhan S, Gera V. Intravenous immunoglobulin for the management of Netherton syndrome. Indian J Dermatol Venereol Leprol 2023;89:754-6

Dear Editor,

Erythroderma indicates generalized erythema and scaling involving more than 80–90% body surface area. There is a long list of differentials for neonatal and infantile erythroderma, including primary immunodeficiency syndromes, ichthyosis, seborrheic dermatitis, atopic dermatitis, psoriasis, langerhan cell histiocytosis, infections like staphylococcal scalded skin syndrome and scabies, drug induced, metabolic and nutritional disorders like biotin metabolism disorders, acrodermatitis enteropathica and urea cycle disorders.1 Netherton syndrome is a rare autosomal recessive disorder characterized by triad of icthyosiform erythroderma, trichorrhexis invaginata and atopic manifestations. Icthyosis linearis cirumflexa represents double-edged scale and is pathognomonic for diagnosing Netherton syndrome, however, it is not a constant feature.2 We present a genetically confirmed case of Netherton syndrome treated with intravenous immunoglobulin.

A 11 months-old-girl, first child of second-degree consanguineous marriage, was brought to us with generalized erythema and scaling involving her body and sparse, dry and fragile hair since birth. She was delivered preterm (32 weeks period of gestation) with low birth weight (2100 gms). None of the family members, first or second degree were suffering from similar problems. There was history of poor weight gain, but vomiting, diarrhoea, malodorous secretions or similar complaints were absent. General examination revealed severe under-nutrition (weight- 5.2 kg, < -3 SD), severe stunting (length- 59 cms, < -3 SD) and microcephaly (occipito-frontal head circumference- 40 cms < -3 SD). Developmental examination suggested global developmental delay with developmental age around nine months. She had no organomegaly. Dermatological examination showed involvement of more than 80% body surface area with erythema and scaling [Figure 1]. Oozing was noted on the flexors of both forearms. Her hair was sparse, dry and fragile. Icthyosis linearis circumflexa was noted [Figure 2]. Trichoscopy demonstrated nodes in the hair shaft and broken hairs of various lengths with a frayed paint-brush-like appearance [Figure 3]. Direct microscopic examination confirmed trichoscopic findings [Figure 4]. Langerhan cell histiocytosis, primary immunodeficiency syndromes, Netherton syndrome and biotinidase deficiency were considered as differential diagnoses. Skin histopathology showed flattened rete pegs, hypogranulosis, mild perivascular lymphocytic infiltrate and absence of CD1a on immunohistochemistry. Laboratory evaluation revealed normal electrolytes, liver and renal function. Her immunodeficiency workup including immunoglobulin profile, lymphocyte subset analysis, complement levels and nitroblue tetrazolium test were normal except for raised serum IgE (510 IU/mL). Serum biotinidase levels were within normal limits. Clinical exome analysis revealed homozygous, single base pair insertion in exon 26 of the SPINK5 gene (chr5:g.148120311_148120312insA; depth: 161x) that resulted in frameshift and premature truncation of the protein, four amino acid downstream to codon 824. This variant was classified as pathogenic in ClinVar database. The mutation was not confirmed by Sanger sequencing. She was treated with multiple courses of oral steroids (1 mg/kg/day), syrup cyclosporine (5 mg/kg/day), topical emollients and mid-potent steroids over the last five months, with partial response. Due to poor response to the first line treatment; continued symptomatology with scaling, severe pruritus and irritability, she was administered intravenous immunoglobulin 400 mg/kg/day every four week. She responded promptly one week after the first cycle and has been under remission on monthly IVIG along with daily emollients and intermittent topical steroids. She has been administered three such cycles and we plan to continue monthly IVIG [Figure 5].

Figure 1:
Erythema and scaling involving more than 80% body surface area. The scaling is more prominent in flexures
Figure 2:
Clinical image shows classical icthyosis linearis circumflexa with double-edged scales
Figure 3:
Trichoscopy shows white scales, nodes on the hair shaft (blue arrow) and broken hairs (polarised dermoscopy, Dermlite DL4 ×10)
Figure 4:
Hair microscopy shows node on the hair shaft (dry mount, ×400)
Figure 5:
Improvement seen after intravenous immunoglobulin

The diagnosis of Netherton syndrome is usually difficult in early infancy as icthyosis linearis cirumflexa is not a constant feature and hair shaft abnormalities may develop later. The diagnosis can be confirmed by genetic studies; however, their cost is prohibitive in resource-poor settings. Netherton syndrome is associated with functional and phenotypic defects in several lymphocyte subpopulations and is classified as a primary immunodeficiency disorder.3 The current treatment options for Netherton syndrome include skin cleansing, antibiotics, bleach bath, topical corticosteroids, calcineurin inhibitors, antihistamines and oral steroids. Retinoids and phototherapy show variable effects. Various other modalities have been tried in recalcitrant cases, not responding to first-line options, and include intravenous immunoglobulin (IVIG), infliximab, secukinumab, ustekinumab, omalizumab and dupilumab.2,4,5 The exact mechanism of action of IVIG in Netherton syndrome is unclear, however, restoration of abnormal antibody response and increased natural killer (NK) cell cytotoxicity may result in its beneficial effect.6 Table 1 highlights the cases of Netherton syndrome which received IVIG. It is difficult to perform large-scale studies for this rare disorder, so evidence regarding new drugs is mostly anecdotal. Intravenous immunoglobulin has achieved success in most cases, and appears to be safe and effective for managing Netherton syndrome, especially those not responding to the first-line treatments.

Table 1: Cases of Netherton syndrome in literature treated with IVIG
Reference Number of patients Dose Follow-up duration Response
Renner ED et al. 7 5 0.4gm/kg/month 2 years Excellent response
Zelieskova M et al. 8 1 0.4 gm/kg/month IV X 3 months followed by 200 mg/kg/month SC 12 months Excellent response
Saenz R et al.9 3 Not mentioned Not mentioned Minimal improvement
Ragamin A et al. 10 2 0.4 gm/Kg/Month 6 month -2.5 years Excellent response lasted 6 month in first patient and 2.5 years in second patient

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent.

Financial support and sponsorship

Nil.

Conflict of interest

There are no conflicts of interest.

References

  1. , , . Neonatal and infantile erythrodermas. Arch Dermatol. 2001;137:822-3.
    [PubMed] [Google Scholar]
  2. , , , , , . Netherton syndrome: Case report and review of the literature. Skin Appendage Disord. 2021;7:346-50.
    [CrossRef] [PubMed] [Google Scholar]
  3. , , , , , , et al. Immune cell phenotype and functional defects in Netherton syndrome. Orphanet J Rare Dis. 2018;13:213.
    [CrossRef] [PubMed] [Google Scholar]
  4. , . Treatment of Netherton syndrome with dupilumab. JAMA Dermatol. 2020;156:350-1.
    [CrossRef] [PubMed] [Google Scholar]
  5. , , , , , , et al. Secukinumab therapy for Netherton syndrome. JAMA Dermatol. 2020;156:907-11.
    [CrossRef] [PubMed] [Google Scholar]
  6. , , , , . Response to low-dose intravenous immunoglobulin in a case of recalcitrant Darier disease. JAAD Case Rep. 2020;6:189-91.
    [CrossRef] [PubMed] [Google Scholar]
  7. , , , , , , et al. Comèl-Netherton syndrome defined as primary immunodeficiency. J Allergy Clin Immunol. 2009;124:536-43.
    [CrossRef] [PubMed] [Google Scholar]
  8. , , , , , . A novel SPINK5 mutation and successful subcutaneous immunoglobulin replacement therapy in a child with Netherton syndrome. Pediatr Dermatol. 2020;37:1202-4.
    [CrossRef] [PubMed] [Google Scholar]
  9. , , , . The difficult management of three patients with Netherton syndrome. Ann Allergy Asthma Immunol. 2018;121:S134.
    [CrossRef] [Google Scholar]
  10. , , , , , . Treatment experiences with intravenous immunoglobulins, ixekizumab, dupilumab, and anakinra in Netherton syndrome: A case series. Dermatology 2022:1-9.
    [CrossRef] [PubMed] [Google Scholar]

Fulltext Views
1,698

PDF downloads
1,288
View/Download PDF
Download Citations
BibTeX
RIS
Show Sections