Trichorrhexis Invaginata (Netherton Syndrome or Bamboo Hair) Clinical Presentation

  • Author: Tina S Chen, MD; Chief Editor: Dirk M Elston, MD   more...
 
Updated: Aug 17, 2011
 

History

  • Erythroderma
    • Most children with Netherton syndrome develop congenital erythroderma, which is evident at birth or during the first weeks of life.
    • Pruritus is universal and can be distressing.
  • Failure to thrive
    • Failure to thrive is often profound in the first year of life and may be accompanied by symptoms of dermopathic enteropathy, which is a nonspecific problem associated with congenital and some acquired erythrodermas. Jejunal villous atrophy has been demonstrated in some patients with Netherton syndrome.
    • By the second year of life, most children improve, although most remain below the 25th percentile for height and weight secondary to malnutrition.
  • Allergic manifestations
    • All patients eventually develop food allergy, particularly to peanuts, eggs, and fish.
    • Most have an atopic predisposition, with a strong family history of asthma, eczema, and hay fever.
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Physical

Netherton syndrome (trichorrhexis invaginata or bamboo hair) has been classified as an ichthyosiform syndrome, but, in most children, the rash appears to be an eczematous dermatitis, with a characteristic periorificial accentuation of the rash. In one study, flexural lichenification was found in all 7 patients, and 2 patients had verrucous hypertrophy of the axillae, the inguinal folds, and the lower legs. Ectropion and taut facial skin can develop in older patients with severe disease.

  • Collodial membrane: This has not been reported in patients with Netherton syndrome. One study reports that colloidal membrane never leads to Netherton syndrome.[16]
  • Ichthyosis linearis circumflexa
    • Ichthyosis linearis circumflexa is a characteristic serpiginous migratory annular/polycyclic rash with double-edged scale. It is pathognomonic for Netherton syndrome.
    • Ichthyosis linearis circumflexa usually occurs after age 2 years and is fairly short-lived, lasting from a few weeks (followed by clearance for months) to years.
    • Ichthyosis linearis circumflexa appears to last longer in adults than in children.
  • Hair features (trichorrhexis invaginata)
    • All patients have sparse, abnormal hair. The hair is short, spiky, lusterless, and brittle.
    • Scalp hair grows for a few centimeters before breaking. This finding is particularly evident at the areas of friction, especially the occiput and the temples. The eyebrows also have sparse, broken hair. Older patients may lose their eyebrows and eyelashes altogether.
    • Some patients also show fragility of the reduced body hair.
    • A few older children have normal-looking hair that is microscopically defective. Identifying the bamboo node on the hair shaft using simple microscopy is necessary because unaided visual detection is practically impossible. Dermatoscopic detection, including videodermoscopic detection,[17] of trichorrhexis invaginata and "matchstick" eyebrow hairs[18] has also been reported, and evaluation of the eyebrows may be easier than the scalp.[19, 20, 21]
    • The relationship with trauma to the severity of hair-shaft defects is probably overemphasized.
    • The severity is likely defined by the gene penetrance and tends to improve with age, but the course can be punctuated by intermittent exacerbations.
    • Pili torti is common.
  • Atopic diathesis: Findings include atopic dermatitis, allergic rhinitis, and asthma.
  • It remains unclear whether patients have an increased susceptibility for skin malignancies such as squamous cell carcinoma.[22]
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Causes

Netherton syndrome is a rare autosomal recessive genodermatosis.

  • Genetics
    • By linkage analysis and homozygosity mapping in 20 families with Netherton syndrome, Chavanas et al[7] mapped the disease locus to 5q32, which is telomeric to the cytokine gene cluster in 5q31. The SPINK5 gene was mapped to the same region of 5q and, for functional reasons, was considered a candidate gene for Netherton syndrome.[23] Mutations in the SPINK5 gene in 13 families with Netherton syndrome were later reported.[24]
    • More than 40 distinct SPINK5 mutations have been reported to the Human Gene Mutation Database, with nonsense, splicing, and small insertions/deletions comprising the majority of them.
  • Biochemical features
    • Chavanas et al[24] studied steady-state levels of the mRNA encoding LEKTI (lymphoepithelial Kazal-type related inhibitor), the gene product of the SPINK5 gene, in cultured epidermal keratinocytes from a healthy control and 5 Netherton syndrome patients. These extracts showed a marked reduction of signal on Northern blot analysis, suggesting nonsense-mediated decay of mutated transcripts, as is frequently observed in recessive disorders.[25]
    • SPINK5 mutations lead to truncated LEKTI, with each Netherton syndrome patient possessing LEKTI of a different length.[11] The multidomain proteinase inhibitor LEKTI consists of 15 potential serine proteinase inhibitory domains. LEKTI domain 15 was found to be identical to that of other known Kazal-type inhibitors.[26]
    • Bitoun et al[27] showed that in contrast to normal skin, LEKTI precursors and proteolytic fragments were not detected in differentiated primary keratinocytes from Netherton syndrome patients. Defective expression of LEKTI in skin sections was a constant feature in Netherton syndrome patients, demonstrating that loss of LEKTI expression in the epidermis is a diagnostic feature of Netherton syndrome.
    • Caspase-1 activity of the stratum corneum and serum interleukin 18 are increased in patients with Netherton syndrome.[26]
    • LEKTI-deficient epidermis leads to unrestricted kallikrein 5 activity, which activates a protease-induced proinflammatory and proallergic pathway: proteinase-activated receptor 2 (PAR2) – mediated expression of pro-Th2 cytokine thymic stromal lymphopoietin.[28]
  • Genotype/phenotype correlations
    • Bitoun et al[29] studied 21 families of different geographic origin and identified 18 mutations, of which 13 were novel and 7 (39%) were recurrent. Five mutations, one of which resulted in perinatal lethal disease in 3 families, were associated with certain ethnic groups. Other lethal variants have also been described.[30]
    • Hachem et al[31] found that serine protease activity and residual LEKTI expression determine a mild, moderate, or severe phenotype in Netherton syndrome. The degree of clinical severity is related to the magnitude of LEKTI activation. Excess LEKTI leads to loss of desmoglein 1 and desmocollin 1, which play a role in both maintaining epidermal integrity and barrier function.
    • Komatsu et al[32] linked LEKTI domain deficiency with clinical manifestations in Japanese Netherton syndrome patients by testing the hypothesis that the varying lengths of LEKTI (depending what mutation was found in the patient) correlated with protease inhibitory activity.
  • Mouse model
    • SPINK5-/- mice exhibit features of Netherton syndrome, including altered desquamation, impaired keratinization, hair malformation, and a skin barrier defect.[33] In this model, LEKTI deficiency leads to abnormal desmosome cleavage in the upper granular layer through desmoglein 1 degradation by stratum corneum tryptic enzyme and stratum corneum chymotryptic enzymelike hyperactivity.
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Contributor Information and Disclosures
Author

Tina S Chen, MD  Pediatric Dermatology Fellow, Rady Children's Hospital, Department of Dermatology, University of California, San Diego

Tina S Chen, MD is a member of the following medical societies: American Academy of Dermatology, California Society of Dermatology and Dermatologic Surgery, and Society for Pediatric Dermatology

Disclosure: Nothing to disclose.

Specialty Editor Board

James W Patterson, MD  Professor of Pathology and Dermatology, Director of Dermatopathology, University of Virginia Medical Center

James W Patterson, MD is a member of the following medical societies: American Academy of Dermatology, American College of Physicians, American Society of Dermatopathology, Royal Society of Medicine, Society for Investigative Dermatology, and United States and Canadian Academy of Pathology

Disclosure: Nothing to disclose.

David F Butler, MD  Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Van Perry, MD  Assistant Professor, Department of Medicine, Division of Dermatology, University of Texas School of Medicine at San Antonio

Van Perry, MD is a member of the following medical societies: American Academy of Dermatology and American Society for Laser Medicine and Surgery

Disclosure: Nothing to disclose.

Glen H Crawford, MD  Assistant Clinical Professor, Department of Dermatology, University of Pennsylvania School of Medicine; Chief, Division of Dermatology, The Pennsylvania Hospital

Glen H Crawford, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Phi Beta Kappa, and Society of USAF Flight Surgeons

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD  Director, Ackerman Academy of Dermatopathology, New York

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Acknowledgments

The author and editors of Medscape Reference gratefully acknowledge the contributions of previous authors, Mohsin Ali, MBBS, FRCP, MRCP, and David T Robles, MD, PhD, to the development and writing of this article.

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