0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Special Feature |

Picture of the Month—Diagnosis FREE

Arch Pediatr Adolesc Med. 2011;165(8):764. doi:10.1001/archpediatrics.2011.120-b.
Text Size: A A A
Published online

DENOUEMENT AND DISCUSSION: COMÈL-NETHERTON SYNDROME WITHOUT BAMBOO HAIR

Direct testing by polymerase chain reaction revealed 2 compound heterozygous mutations of the serine protease inhibitor Kazal-type 5 gene (SPINK5) in the proband, one present in his mother and the other in his father. A diagnosis of Comèl-Netherton syndrome was made.

Comèl-Netherton syndrome (OMIM #256500) is an autosomal recessive disease caused by mutations of the SPINK5 gene1 and characterized by the triad of ichthyosis linearis circumflexa, trichorrhexis invaginata, and atopic diathesis. The incidence of Comèl-Netherton syndrome is approximately 1 in 200 000 persons per year. Comèl-Netherton syndrome is also thought to be the cause of up to 18% of congenital erythrodermas2; mortality, mostly due to infections or electrolyte imbalance, is highest during the first year of life. Most patients have mutations in the SPINK5 gene, located on chromosome 5q32, resulting in a loss or reduced expression of the multidomain serine protease inhibitor lymphoepithelial Kazal-type 5 related inhibitor (LEKTI). LEKTI has been proposed to downregulate desquamation and matrix maturation. LEKTI is expressed by epithelial cells of skin, mucosa, and Hassall corpuscles, raising the possibility that LEKTI affects T-cell maturation.3 Although generally not listed among primary immunodeficiencies, a recent study strongly suggests that Comèl-Netherton syndrome is a multisystem disorder associated with dysfunctional innate and cognate immunity.3

The extent of early skin findings of Comèl-Netherton syndrome can vary greatly. Patients with more severe cases are born with collodion membrane or congenital ichthyosiform erythroderma.2 The initial eruption usually evolves over time into ichthyosis linearis circumflexa, which consists of migratory polycyclic erythematous patches surrounded by a serpiginous overlying double-edged scale.

Trichorrhexis invaginata (also called bamboo hair) is a focal defect of the hair shaft that produces development of torsion nodules and invaginated nodules. The proximal element of the node overlaps the distal portion, causing an intussusception.2 If hair is pulled distally from this focal defect, a golf tee–like deformity is left. Hence, any hairs examined should be cut rather than plucked. The hair shaft nodules caused by this defect are sometimes seen by the naked eye. These hair defects can be found on the scalp but are most common on the eyebrows or eyelashes. Grossly, scalp hair is described as sparse and brittle with patchy thinning. Hair growth often improves with age, and the hair defects can completely resolve. The presence of trichorrhexis invaginata is required to make the diagnosis. However, the manifestations of the disorder are quite protean even in the same patient over time. Neither the skin nor the hair may have a characteristic appearance at birth, and with age the hair defects may disappear.

Besides an atopic dermatitis–like picture, atopic diathesis can include asthma, allergic rhinitis, food allergy, urticaria or angioedema, and anaphylactoid reactions. Other clinical features include mental deficiency, neurologic deficits (either seizure disorders or spastic diplegia), failure to thrive, delayed growth and body development, short stature, recurrent infections (skin, eye, upper or lower respiratory tract), aminoaciduria, heat intolerance, hypogammaglobulinemia, or hypergammaglobulinemia.

The main differential diagnosis is with atopic dermatitis (mainly severe, long-lasting, and/or treatment-resistant forms). Ichthyosis linearis circumflexa and/or trichorrhexis invaginata allow a high index of suspicion when present. Genetic testing is usually required to confirm the diagnosis. Other entities to consider are neonatal and childhood erythrodermas (including seborrheic dermatitis and congenital ichthyoses) and immunodeficiency-associated dermatitis or erythroderma (such as in common variable immunodeficiency and hyper-IgE syndromes).

Many treatments have been attempted for skin manifestations of Comèl-Netherton syndrome. Topical corticosteroids are inconsistently successful. Other treatments include lactate lotion, 12%,4 calcineurin inhibitors (tacrolimus and pimecrolimus),5 and isotretinoin.6 Patients with Comèl-Netherton syndrome are likely more susceptible to systemic absorption of medication and are potentially at increased risk to experience adverse reactions to topical therapies. Oral treatments include low-dose oral corticosteroids, etretinate, and psoralen UV-A therapy.2

Return to Quiz Case.

Correspondence: Daniele Torchia, MD, PhD, University of Miami Hospital, 1295 NW 14th St, Ste K, Miami, FL 33125 (dtorchia@med.miami.edu).

Accepted for Publication: October 13, 2010.

Author Contributions:Study concept and design: Torchia and Schachner. Acquisition of data: Torchia and Schachner. Analysis and interpretation of data: Torchia and Schachner. Drafting of the manuscript: Torchia. Critical revision of the manuscript for important intellectual content: Torchia and Schachner. Study supervision: Schachner.

Financial Disclosure: None reported.

Chavanas S, Bodemer C, Rochat A,  et al.  Mutations in SPINK5, encoding a serine protease inhibitor, cause Netherton syndrome.  Nat Genet. 2000;25(2):141-142
PubMed   |  Link to Article
Sun JD, Linden KG. Netherton syndrome.  Int J Dermatol. 2006;45(6):693-697
PubMed   |  Link to Article
Smith DL, Smith JG, Wong SW, deShazo RD. Netherton's syndrome.  J Allergy Clin Immunol. 1995;95(1, pt 1):116-123
PubMed   |  Link to Article
Wehr RF, Hickman J, Krochmal L. Effective treatment of Netherton's syndrome with 12% lactate lotion.  J Am Acad Dermatol. 1988;19(1, pt 1):140-142
PubMed   |  Link to Article
Lazaridou E, Apalla Z, Patsatsi A, Trigoni A, Ioannides D. Netherton's syndrome: successful treatment with isotretinoin.  J Eur Acad Dermatol Venereol. 2009;23(2):210-212
PubMed   |  Link to Article
Yan AC, Honig PJ, Ming ME, Weber J, Shah KN. The safety and efficacy of pimecrolimus, 1%, cream for the treatment of Netherton syndrome: results from an exploratory study.  Arch Dermatol. 2010;146(1):57-62
PubMed   |  Link to Article

Figures

Tables

References

Chavanas S, Bodemer C, Rochat A,  et al.  Mutations in SPINK5, encoding a serine protease inhibitor, cause Netherton syndrome.  Nat Genet. 2000;25(2):141-142
PubMed   |  Link to Article
Sun JD, Linden KG. Netherton syndrome.  Int J Dermatol. 2006;45(6):693-697
PubMed   |  Link to Article
Smith DL, Smith JG, Wong SW, deShazo RD. Netherton's syndrome.  J Allergy Clin Immunol. 1995;95(1, pt 1):116-123
PubMed   |  Link to Article
Wehr RF, Hickman J, Krochmal L. Effective treatment of Netherton's syndrome with 12% lactate lotion.  J Am Acad Dermatol. 1988;19(1, pt 1):140-142
PubMed   |  Link to Article
Lazaridou E, Apalla Z, Patsatsi A, Trigoni A, Ioannides D. Netherton's syndrome: successful treatment with isotretinoin.  J Eur Acad Dermatol Venereol. 2009;23(2):210-212
PubMed   |  Link to Article
Yan AC, Honig PJ, Ming ME, Weber J, Shah KN. The safety and efficacy of pimecrolimus, 1%, cream for the treatment of Netherton syndrome: results from an exploratory study.  Arch Dermatol. 2010;146(1):57-62
PubMed   |  Link to Article

Correspondence

CME
Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

See Also...
Articles Related By Topic
Related Collections