THE S Y ~ D ~ O PAGE ~ E Pediatric Dermatology Vol. 9 No. 2 157-160
Editors: Susan B. Mallory, M.D., and Bernice R. Krafchik, M.B., Ch.B., F.R.C.P.(C)
What Syndrome Is This?
Figure 1. Erythema and scaling, especially noticable around the mouth and in the perineal areas of the patient.
Figure 2. Typical erythema in our patient at age 5 years.
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158 Pediatric Dermatology Vol. 9 No. 2 June 1992
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Figure 3. Scanning electron microscopy of an abnormal hair shaft.
Figure 4. lchthyosis linearis circurnflexa.
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Figure 5. Spiky characteristic hair.
A newborn girl was seen by the dermatology service for erythroderma (Fig. 1) and failure to thrive. The mother’s pregnancy had been uneventful, and there was no parental consanguinity. The infant’s extensive work-up included complete blood cell count, erythrocyte sedimentation rate, serum zinc, serum immunoglobulins and IgE, biotinadase estimation, G5 estimation, skin biopsy, phytanic acid estimation, urinary organic acids, vitamins A and E, and sweat chloride test. The results were ail negative. While in hospital she developed hypernatremia despite good fluid balance and no other ascertainable cause. During the following three years she continued to
~
The Syndrome Page
exhibit erythroderma and slight motor delay. She had a number of chest and skin infections that responded well to antibiotics. We examined her hair on a few occasions, with negative results. At age 5 years (Fig. 2) she was discussed at the Society of Pediatric Dermatology meeting in Quebec with no consensus as to diagnosis. At that time she was thin and had a generalized eruption that consisted of erythema and scaling, particularly marked around the mouth and in the perineal area. Her motor skills had improved and were average for her age group. On a routine visit another hair pull revealed an abnormality in the hair shaft that was quite characteristic on scanning electron microscopy {Fig. 3), NETHERTON SYNDROME
In 1949 Come1 described a woman with skin lesions suggestive of ichthyosis linearis circumflexa (ILC). Netherton in 1958 described a young girl with erythroderma and abnormal hair. The hair abnormality was named trichorrhexis invaginata (TI) by Wilkerson in 1964. The syndrome consists of three features: an erythroderma or, more commonly, ILC; a specific hair shaft abnormality-TI-with at times pili torti and trichorrhexis nodosa; and an atopic diathesis. Other inconsistent features are aminoaciduria, mental retardation, recurrent infections, delayed growth and development, and nonspecific immune defects. The sex ratio is probably equal, although in some reviews females predominate, possibly because abnormal hair is not as acceptable in females as in males. The inheritance is autosomal recessive, with a few reports of the disease in siblings. Erythroderma is the first sign of the syndrome and is generally designated congenital nonbullous ichthyosiform erythroderma. Since our presentation a number of other reports have confirmed this feature. In infancy this may be associated with failure to thrive, and many patients experience marked hypernatremia that is not accounted for by prematurity, fluid imbalance, diarrhea, or renal problems. The eruption is particularly marked around the mouth, eyes, and perineal area, often leading to the erroneous diagnosis of acrodermatitis enteropathica. Other differential diagnoses are acrodermatitis enteropathica, congenital ichthyosiform erythroderma, biotin deficiency, Leiner disease, and Refsum syndrome. Ichthyosis linearis circumflexa may not become evident for a number of years, and consists of a double-edged scale with a serpiginous border sur-
159
rounding erythematous, polycyclic, migratory patches {Fig. 4). The eruption is not usually pruritic. A distinctive histologic feature involves an accumulation of an eosinophilic, periodic acid-Schiff, Sudan positive material focally replacing the stratum corneum at the active border of the skin lesions. This is thought to be a glycoprotein. Others d o not accept this as a diagnostic sign and describe this feature in psoriasis. One aspect that has not been emphasized is the remarkable erythroderma that follows any infection. Parents notice coarse, lusterless hair with a thick scale that is difficult to remove. The hairs may break off or stand on end, and are short and brittle (Fig. 5). The diagnostic abnormality is an invagination of the distal end of the hair shaft into the proximal end that is best seen on scanning electron microscopy. Pinkus postulated a transient disturbance of keratinization of hair growth, but the actual defect is unknown. Meticulous hair pulling may reveal the abnormal hairs that may even affect vellus hairs, but a high index of suspicion is necessary. On unassisted examination, the abnormal hair is angled at the nodose swelling. Although TI is the diagnostic hair abnormality, pili torti and trichorrhexis nodosa may also be found in patients with Netherton syndrome. The atopic diathesis consists of urticaria, angioneurotic edema {usually from peanut ingestion), atopic dermatitis, asthma, allergic rhinitis, and an elevated serum IgE, all nonspecific features. Lichenified lesions in the ante cubit^ fossae are not unusual. Aminoaciduria is an inconstant finding and is described as transient in most patients. Greene and Muller suggested that this feature may be related to the use of steroids, but it has also occurred when steroids were not used. Treatment with a variety of agents has not shown any consistent improvement and no cure. Psoralen and ultraviolet A light is reported to have helped the skin lesions, but treatment must be maintained. Etretinate has been effective in some cases but other reports describe a marked worsening of the lesions at the initiation of therapy. Lactic acid 12% shows impressive improvement in some patients. Many other topical emollients and steroid applications provide temporary mild improvement. CONCLUSION
Netherton syndrome is a well-described disease entity. Recently a number of features have been rec-
o ~ y9 No. 2 June 1992 160 Pediatric ~ e r ~ a t o l Vol.
ognized that have not previously been stressed. The disease is always present in the first 10 days of life, and the skin findings at this time are those of an erythr o d e m , Hair e ~ ~ ~ n ashouid t i o ~ he carried out ~ ~costly~~nv~stigation~. ~ e Hy-s eady to avoid ~ pematremia sfiouid be monitrtred, as this has been a feature of many reports atld, a ~ it may~ repre-~ sent water loss as in any erythroderma, this seems to occur with increased frequency in patients with Netherton syndrome. Finally, an erythroderma that may be difficult to control is often seen in patients who have an infection associated with the syndrome.
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I. Greene SL and Muller SA. Nethenon’s syndrome: Report of a case and review of the literature. JAAD 1985;3 3 :2(part 2):32%3 36. 2 . Krafchik BR and Toole JWP. What is Netherton’s Syndrome? Inter J Dermatol 1983;22:45!&-462. 3. Plantin P, Defaire P, Guillet MH, Lobouche F, Guile: A ~ K N ~ ~ L ~ D ~ ~ ~ N T let G. New Aspects of Netherton‘s S y n d ~ o ~Nine cases. Ann Dermatot Venereal 1991;J t8:S25-530. We acknowledge with thanks the support of West4. Jones SK, Thomason LM, Surbrigg SK, Weston WL. wood Pharmaceuticals in u ~ d e ~ r i t the i n ~cost of Neonatal hypernatraemia in two siblings with Nethcolor illustrations for this section of the journal. erron’s syndrome. Br J Dermatol 1986;114:741-743.
CALL FUR PAPERS
The editors of the ~ ~ d r Page ~ Iwelcome ~ e s u b ~ ~ ~ sofs iyour o ~ ~ ~ R ~ s ~ rfor j p~t os n s ~ ~ ePlease r a ~ submit ~ ~ . them. in triplicate to: Susan B. ~ a I l oM.D., ~ , ~ e p aof ~~ ~~ ~ a ~ tSt. t ~ Louisl Children’s o ~ Hospital, ~ 400 S . Kingshighway, St. Louis, MO 631 10
Editors: Susan B. Mallory, M.D., and Bernice R. Krafchik, M.B., Ch.B., F.R.C.P.(C)
What Syndrome Is This?
Figure 1. Erythema and scaling, especially noticable around the mouth and in the perineal areas of the patient.
Figure 2. Typical erythema in our patient at age 5 years.
157
158 Pediatric Dermatology Vol. 9 No. 2 June 1992
~
~
Figure 3. Scanning electron microscopy of an abnormal hair shaft.
Figure 4. lchthyosis linearis circurnflexa.
t S y h~ d r ~u m ~~
t
~
Figure 5. Spiky characteristic hair.
A newborn girl was seen by the dermatology service for erythroderma (Fig. 1) and failure to thrive. The mother’s pregnancy had been uneventful, and there was no parental consanguinity. The infant’s extensive work-up included complete blood cell count, erythrocyte sedimentation rate, serum zinc, serum immunoglobulins and IgE, biotinadase estimation, G5 estimation, skin biopsy, phytanic acid estimation, urinary organic acids, vitamins A and E, and sweat chloride test. The results were ail negative. While in hospital she developed hypernatremia despite good fluid balance and no other ascertainable cause. During the following three years she continued to
~
The Syndrome Page
exhibit erythroderma and slight motor delay. She had a number of chest and skin infections that responded well to antibiotics. We examined her hair on a few occasions, with negative results. At age 5 years (Fig. 2) she was discussed at the Society of Pediatric Dermatology meeting in Quebec with no consensus as to diagnosis. At that time she was thin and had a generalized eruption that consisted of erythema and scaling, particularly marked around the mouth and in the perineal area. Her motor skills had improved and were average for her age group. On a routine visit another hair pull revealed an abnormality in the hair shaft that was quite characteristic on scanning electron microscopy {Fig. 3), NETHERTON SYNDROME
In 1949 Come1 described a woman with skin lesions suggestive of ichthyosis linearis circumflexa (ILC). Netherton in 1958 described a young girl with erythroderma and abnormal hair. The hair abnormality was named trichorrhexis invaginata (TI) by Wilkerson in 1964. The syndrome consists of three features: an erythroderma or, more commonly, ILC; a specific hair shaft abnormality-TI-with at times pili torti and trichorrhexis nodosa; and an atopic diathesis. Other inconsistent features are aminoaciduria, mental retardation, recurrent infections, delayed growth and development, and nonspecific immune defects. The sex ratio is probably equal, although in some reviews females predominate, possibly because abnormal hair is not as acceptable in females as in males. The inheritance is autosomal recessive, with a few reports of the disease in siblings. Erythroderma is the first sign of the syndrome and is generally designated congenital nonbullous ichthyosiform erythroderma. Since our presentation a number of other reports have confirmed this feature. In infancy this may be associated with failure to thrive, and many patients experience marked hypernatremia that is not accounted for by prematurity, fluid imbalance, diarrhea, or renal problems. The eruption is particularly marked around the mouth, eyes, and perineal area, often leading to the erroneous diagnosis of acrodermatitis enteropathica. Other differential diagnoses are acrodermatitis enteropathica, congenital ichthyosiform erythroderma, biotin deficiency, Leiner disease, and Refsum syndrome. Ichthyosis linearis circumflexa may not become evident for a number of years, and consists of a double-edged scale with a serpiginous border sur-
159
rounding erythematous, polycyclic, migratory patches {Fig. 4). The eruption is not usually pruritic. A distinctive histologic feature involves an accumulation of an eosinophilic, periodic acid-Schiff, Sudan positive material focally replacing the stratum corneum at the active border of the skin lesions. This is thought to be a glycoprotein. Others d o not accept this as a diagnostic sign and describe this feature in psoriasis. One aspect that has not been emphasized is the remarkable erythroderma that follows any infection. Parents notice coarse, lusterless hair with a thick scale that is difficult to remove. The hairs may break off or stand on end, and are short and brittle (Fig. 5). The diagnostic abnormality is an invagination of the distal end of the hair shaft into the proximal end that is best seen on scanning electron microscopy. Pinkus postulated a transient disturbance of keratinization of hair growth, but the actual defect is unknown. Meticulous hair pulling may reveal the abnormal hairs that may even affect vellus hairs, but a high index of suspicion is necessary. On unassisted examination, the abnormal hair is angled at the nodose swelling. Although TI is the diagnostic hair abnormality, pili torti and trichorrhexis nodosa may also be found in patients with Netherton syndrome. The atopic diathesis consists of urticaria, angioneurotic edema {usually from peanut ingestion), atopic dermatitis, asthma, allergic rhinitis, and an elevated serum IgE, all nonspecific features. Lichenified lesions in the ante cubit^ fossae are not unusual. Aminoaciduria is an inconstant finding and is described as transient in most patients. Greene and Muller suggested that this feature may be related to the use of steroids, but it has also occurred when steroids were not used. Treatment with a variety of agents has not shown any consistent improvement and no cure. Psoralen and ultraviolet A light is reported to have helped the skin lesions, but treatment must be maintained. Etretinate has been effective in some cases but other reports describe a marked worsening of the lesions at the initiation of therapy. Lactic acid 12% shows impressive improvement in some patients. Many other topical emollients and steroid applications provide temporary mild improvement. CONCLUSION
Netherton syndrome is a well-described disease entity. Recently a number of features have been rec-
o ~ y9 No. 2 June 1992 160 Pediatric ~ e r ~ a t o l Vol.
ognized that have not previously been stressed. The disease is always present in the first 10 days of life, and the skin findings at this time are those of an erythr o d e m , Hair e ~ ~ ~ n ashouid t i o ~ he carried out ~ ~costly~~nv~stigation~. ~ e Hy-s eady to avoid ~ pematremia sfiouid be monitrtred, as this has been a feature of many reports atld, a ~ it may~ repre-~ sent water loss as in any erythroderma, this seems to occur with increased frequency in patients with Netherton syndrome. Finally, an erythroderma that may be difficult to control is often seen in patients who have an infection associated with the syndrome.
s
~
o
~
~
~
I. Greene SL and Muller SA. Nethenon’s syndrome: Report of a case and review of the literature. JAAD 1985;3 3 :2(part 2):32%3 36. 2 . Krafchik BR and Toole JWP. What is Netherton’s Syndrome? Inter J Dermatol 1983;22:45!&-462. 3. Plantin P, Defaire P, Guillet MH, Lobouche F, Guile: A ~ K N ~ ~ L ~ D ~ ~ ~ N T let G. New Aspects of Netherton‘s S y n d ~ o ~Nine cases. Ann Dermatot Venereal 1991;J t8:S25-530. We acknowledge with thanks the support of West4. Jones SK, Thomason LM, Surbrigg SK, Weston WL. wood Pharmaceuticals in u ~ d e ~ r i t the i n ~cost of Neonatal hypernatraemia in two siblings with Nethcolor illustrations for this section of the journal. erron’s syndrome. Br J Dermatol 1986;114:741-743.
CALL FUR PAPERS
The editors of the ~ ~ d r Page ~ Iwelcome ~ e s u b ~ ~ ~ sofs iyour o ~ ~ ~ R ~ s ~ rfor j p~t os n s ~ ~ ePlease r a ~ submit ~ ~ . them. in triplicate to: Susan B. ~ a I l oM.D., ~ , ~ e p aof ~~ ~~ ~ a ~ tSt. t ~ Louisl Children’s o ~ Hospital, ~ 400 S . Kingshighway, St. Louis, MO 631 10
