Journal of Tropical Pediatrics Advance Access published January 7, 2015 Journal of Tropical Pediatrics, 2014, 0, 1–3 doi: 10.1093/tropej/fmu072 Case Report
CASE REPORT
Harlequin Ichthyosis in an Infant Born to a Father with Eczema 1
Department of Pediatrics, Civil Hospital Karachi, Karachi, Pakistan, 74200 Department of Dermatology, Civil Hospital Karachi, Karachi, Pakistan, 74200 Correspondence: Zain Majid, 147-B/1, Khe-e-Bahria, Phase-VII, D.H.A, Karachi, Pakistan, 75500. E-mail: 2
SU M MAR Y Harlequin ichthyosis is characterized by thickening of the layer of the skin which contains keratin. Eczema is a chronic relapsing skin disorder which is also associated with disrupted epidermal barrier. We report the case of a 6-hour-old male patient who was brought to the neonatal intensive care unit of our hospital with crusting skin lesions all over the body, presence of a severe ectropion and deranged electrolytes. A diagnosis of harlequin ichthyosis was made, and the neonate was managed accordingly. However, the infant eventually expired on the seventh day of life. The infant’s father was a patient of eczema with a chronic relapsing course and was on oral steroid therapy. As per our knowledge, this is the first reported case of an infant with harlequin ichthyosis born to a father suffering from eczema. The similarities in the pathogenesis of the two diseases and the genetic mutation of filaggrin might suggest an association between the two conditions. Harlequin ichthyosis can hence be looked out for in infants born of parents with eczema. K E Y W O R D S : harlequin ichthyosis, eczema, pediatric dermatology, neonate.
INTRODUCTION Harlequin ichthyosis presents with a thick shell-like mass over the body, separated by erythematous fissures. It is also associated with severe ectropion, nasal hypoplasia, rudimentary ears, eclabium and circumferential constriction of the limbs [1]. Eczema is a chronic relapsing skin disorder which is also associated with disrupted epidermal barrier. Its pathogenesis is associated with both genetics and environment [2]. It is characterized by pruritic papules and vesicles covered by exudates. In chronic disease, eczema presents with dry plaques due to excessive lichenification. It is associated with a Immunoglobulin E (IgE)-mediated response to food and allergens [3].
CASE REPORT A 6-hour-old male weighing 2.8 kg was brought to the neonatal intensive care unit with crusting skin lesions all over the body. He was the second child from a consanguineous marriage and was a booked case at the same hospital. Mother had three ultrasound scans done during pregnancy, and the one done in the third trimester demonstrated polyhydramnios. The mother reported a subjective feeling of decreased fetal movements during pregnancy. The baby was born full term at 37 weeks through emergency lower-segment caesarian section due to breech position. Baby cried immediately after birth and there was no history of central or peripheral
C The Author [2014]. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected] V
1
Downloaded from http://tropej.oxfordjournals.org/ at Warsaw University on January 16, 2015
by Saba Fatima,1 Ali Rafiq2 and Zain Majid1
2
Harlequin Ichthyosis in an Infant Born to a Father with Eczema
cyanosis. Apgar scores at 1 and 5 minutes were 8 and 10, respectively. On examination, heart rate was 125 bpm, respiratory rate 42 breaths per minute and temperature was 98.2 F. The skin revealed hard, thickened, yellow and crusting diamond-shaped plaques separated by erythematous fissures. Eyes showed severe ectropion, leaving no visualization of the cornea and sclera. Ears were crumpled and not well formed. Mouth showed severe eclabium. Nasal bridge was depressed with patent anterior nares. Limbs were edematous, firm and smooth, with no syndactyly or polydactyly. Limb motility was poor. Genitalia were male and underdeveloped, with peeling skin. Anus was patent with crusting lesions present. Systemic examination was unremarkable with no signs of respiratory distress. Primitive reflexes such as Moro could not be assessed due to stiffness of skin. Suck was poor. Laboratory examinations showed deranged electrolytes. Naþ, Kþ, Cl and Ca2þ were 113, 2.8, 106 and 6 meq/L, respectively. Remaining investigations were unremarkable. Eye examination revealed presence of the lens and eyeball and no internal abnormalities. Ultrasound abdomen revealed no fluid accumulation or visceromegaly. Patient was immediately managed by umbilical catheterization and fluid replacement. Incubator care was provided to avoid hypothermia. Intravenous antibiotics were started prophylactically to prevent infection. Liquid paraffin was applied over entire skin, and eyes were lubricated with ointment. Orogastric
DISCUSSION Harlequin ichthyosis is the most severe form of autosomal recessive congenital ichthyosis, with an incidence of 1 in 300 000 births [4]. It has no racial or ethnic predilection [5]. Infants with harlequin ichthyosis face difficulties maintaining electrolytes and water balance due to defective skin barrier. Hence, these infants are often dehydrated with deranged electrolytes. Electrolytes were seen to be initially deranged in the case we have reported as well. Respiratory compromise is also one of the complications faced by such patients due to restriction of the chest wall by the thick skin barrier. In patients who survive, the hyperkeratotic scale is shed in the initial few months, leaving erythematous skin covering the body [1]. Respiratory distress became the eventual cause of death in the case we hereby report. Studies have shown that mutations in the ABCA12 gene encoding a protein for lipid transport in the skin are involved in the pathogenesis of the disease. The ABCA12 gene encodes a protein involved in lipid transport across the epidermis of the skin. In harlequin ichthyosis, the transfer of lipid from the cytosol to the lamellar granules is absent [6]. The abnormality in the lamellar granules results in defective skin
Downloaded from http://tropej.oxfordjournals.org/ at Warsaw University on January 16, 2015
Fig. 1. A newborn showing the signs of Harlequin ichthyosis.
feeding was started on the second day of life and was tolerated well by the patient. Electrolytes returned to normal on the third day of life. Scales had started to shed off and erythematous skin was visible. A discharge was evident on some parts of the plaques on the skin. The patient expired on the seventh day of life due to respiratory distress. A postmortem study could not be conducted due to consent reasons. There was a history of death of a prior sibling with same condition on the third day of life. The father of the baby was a 35-year-old suffering from eczema that pursued a chronic relapsing course. He had first reported his skin ailment 12 years ago and had approached various general practitioners and dermatologists for its treatment. The eczematous lesions mostly surrounded his ankles, knees and elbows. Currently, he was on oral steroid therapy that had been prescribed to him by a general practitioner in his neighborhood. The father also reported that one of his siblings had a similar skin disease as himself.
Harlequin Ichthyosis in an Infant Born to a Father with Eczema
3
Moreover, harlequin ichthyosis can be expected in babies who are product of consanguineous marriage, have eczema in one of the parents and display polyhydramnios on ultrasound in the third trimester of pregnancy. This will enable the pediatric units to be better equipped to deal with such a condition.
CONCLUSION The similarities in the pathogenesis of harlequin ichthyosis and eczema and the genetic mutation of filaggrin might suggest an association between the two conditions. Harlequin ichthyosis can hence be looked out for in infants of parents with eczema, especially when accompanied with abnormal ultrasonographic findings in the third trimester of pregnancy.
REFERENCES 1. Harvey HB, Shaw MG, Morrell DS. Perinatal management of harlequin ichthyosis: a case report and literature review. J Perinatol 2010;30:66–72. 2. Sohn A, Frankel A, Patel RV, et al. Eczema. Mt Sinai J Med 2011;78:730–9. 3. Sabin BR, Peters N, Peters AT. Chapter 20: atopic dermatitis. Allergy Asthma Proc 2012;33(Suppl. 1):S67–9. 4. Gurses D, Kilic I, Baskan M. A case of harlequin fetus with psoriasis in his family. Internet J Hematol 2000;1:1. 5. Rajpopat S, Moss C, Mellerio J, et al. Harlequin ichthyosis: a review of clinical and molecular findings in 45 cases. Arch Dermatol 2011;147:681–6. 6. Kelsell DP, Norgett EE, Unsworth H, et al. Mutations in ABCA12 underlie the severe congenital skin disease harlequin ichthyosis. Am J Hum Genet 2005;76:794–803. 7. Omidi AA, Katebi M, Ghannad Kafi SH, et al. Harlequin ichthyosis: a report of two cases. Iranian J Dermatol 2005; 8:54–6. 8. Habib A, Pasha W, Raza N, et al. Harlequin ichthyosis in two siblings. J Coll Physicians Surg Pak 2011;21:503–5. 9. Ring J, Mo¨hrenschlager M, Weidinger S. Molecular genetics of atopic eczema. Chem Immunol Allergy 2012;96: 24–9. 10. Thyssen JP, Godoy-Gijon E, Elias PM. Ichthyosis vulgaris: the filaggrin mutation disease. Br J Dermatol 2013;168: 1155–66. 11. Lakshmi C, Srinivas CR. Hand eczema: an update. Indian J Dermatol Venereol Leprol 2012;78:569–82.
Downloaded from http://tropej.oxfordjournals.org/ at Warsaw University on January 16, 2015
permeability and the complications associated with harlequin ichthyosis. Harlequin ichthyosis is associated with high morbidity and mortality [5]. However, the use of oral retinoids which aid in the shedding of the hyperkeratotic scale has given a hope for its management. In a study conducted by Rajpot et al. [5] on 45 cases of harlequin babies, 20 of the 24 patients (83%) who were given oral retinoids survived. With good palliative care, the survival rate in the overall 45 cases was more than 50%. Supportive therapy for such babies includes fluid and electrolyte management, humidification, prevention of infection, lubrication and prevention of desiccation of the eyes. Considering the predominant inheritance pattern of this disease, which is autosomal recessive, consanguinity is an important risk factor of this condition. There have been reports of siblings of consanguineous parents affected with this disorder [7, 8]. Skin diseases in parents have also been stated as a possible risk factor. A case of a father with psoriasis has been reported [4]. In our case the father of the baby was suffering from eczema. Genetic predisposition to eczema is associated with mutation in epidermal protein filaggrin on chromosome 1 [9]. This mutation is associated with defective epidermal barrier. The protein filaggrin is also vital in maintaining effective skin barrier. Mutations in the filaggrin gene are also associated with an autosomal dominant genetic disorder and a milder form of ichthyosis, hereditary ichthyosis vulgaris [10]. Ichthyosis vulgaris is associated with xerosis, scaling, hyperkeratosis and a relationship to atopic disorders. Oral retinoids also have a role in the treatment of chronic hand eczema [11]. As per our knowledge, there has been no reported case of a child with harlequin ichthyosis born to parents suffering from eczema. The similarities in the pathogenesis in the form of a defective epidermal barrier and the common gene mutation of filaggrin in a milder form of ichthyosis and eczema may imply a possible relationship between these two conditions. Eczema can emerge as a risk factor in parents for harlequin babies.
CASE REPORT
Harlequin Ichthyosis in an Infant Born to a Father with Eczema 1
Department of Pediatrics, Civil Hospital Karachi, Karachi, Pakistan, 74200 Department of Dermatology, Civil Hospital Karachi, Karachi, Pakistan, 74200 Correspondence: Zain Majid, 147-B/1, Khe-e-Bahria, Phase-VII, D.H.A, Karachi, Pakistan, 75500. E-mail: 2
SU M MAR Y Harlequin ichthyosis is characterized by thickening of the layer of the skin which contains keratin. Eczema is a chronic relapsing skin disorder which is also associated with disrupted epidermal barrier. We report the case of a 6-hour-old male patient who was brought to the neonatal intensive care unit of our hospital with crusting skin lesions all over the body, presence of a severe ectropion and deranged electrolytes. A diagnosis of harlequin ichthyosis was made, and the neonate was managed accordingly. However, the infant eventually expired on the seventh day of life. The infant’s father was a patient of eczema with a chronic relapsing course and was on oral steroid therapy. As per our knowledge, this is the first reported case of an infant with harlequin ichthyosis born to a father suffering from eczema. The similarities in the pathogenesis of the two diseases and the genetic mutation of filaggrin might suggest an association between the two conditions. Harlequin ichthyosis can hence be looked out for in infants born of parents with eczema. K E Y W O R D S : harlequin ichthyosis, eczema, pediatric dermatology, neonate.
INTRODUCTION Harlequin ichthyosis presents with a thick shell-like mass over the body, separated by erythematous fissures. It is also associated with severe ectropion, nasal hypoplasia, rudimentary ears, eclabium and circumferential constriction of the limbs [1]. Eczema is a chronic relapsing skin disorder which is also associated with disrupted epidermal barrier. Its pathogenesis is associated with both genetics and environment [2]. It is characterized by pruritic papules and vesicles covered by exudates. In chronic disease, eczema presents with dry plaques due to excessive lichenification. It is associated with a Immunoglobulin E (IgE)-mediated response to food and allergens [3].
CASE REPORT A 6-hour-old male weighing 2.8 kg was brought to the neonatal intensive care unit with crusting skin lesions all over the body. He was the second child from a consanguineous marriage and was a booked case at the same hospital. Mother had three ultrasound scans done during pregnancy, and the one done in the third trimester demonstrated polyhydramnios. The mother reported a subjective feeling of decreased fetal movements during pregnancy. The baby was born full term at 37 weeks through emergency lower-segment caesarian section due to breech position. Baby cried immediately after birth and there was no history of central or peripheral
C The Author [2014]. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected] V
1
Downloaded from http://tropej.oxfordjournals.org/ at Warsaw University on January 16, 2015
by Saba Fatima,1 Ali Rafiq2 and Zain Majid1
2
Harlequin Ichthyosis in an Infant Born to a Father with Eczema
cyanosis. Apgar scores at 1 and 5 minutes were 8 and 10, respectively. On examination, heart rate was 125 bpm, respiratory rate 42 breaths per minute and temperature was 98.2 F. The skin revealed hard, thickened, yellow and crusting diamond-shaped plaques separated by erythematous fissures. Eyes showed severe ectropion, leaving no visualization of the cornea and sclera. Ears were crumpled and not well formed. Mouth showed severe eclabium. Nasal bridge was depressed with patent anterior nares. Limbs were edematous, firm and smooth, with no syndactyly or polydactyly. Limb motility was poor. Genitalia were male and underdeveloped, with peeling skin. Anus was patent with crusting lesions present. Systemic examination was unremarkable with no signs of respiratory distress. Primitive reflexes such as Moro could not be assessed due to stiffness of skin. Suck was poor. Laboratory examinations showed deranged electrolytes. Naþ, Kþ, Cl and Ca2þ were 113, 2.8, 106 and 6 meq/L, respectively. Remaining investigations were unremarkable. Eye examination revealed presence of the lens and eyeball and no internal abnormalities. Ultrasound abdomen revealed no fluid accumulation or visceromegaly. Patient was immediately managed by umbilical catheterization and fluid replacement. Incubator care was provided to avoid hypothermia. Intravenous antibiotics were started prophylactically to prevent infection. Liquid paraffin was applied over entire skin, and eyes were lubricated with ointment. Orogastric
DISCUSSION Harlequin ichthyosis is the most severe form of autosomal recessive congenital ichthyosis, with an incidence of 1 in 300 000 births [4]. It has no racial or ethnic predilection [5]. Infants with harlequin ichthyosis face difficulties maintaining electrolytes and water balance due to defective skin barrier. Hence, these infants are often dehydrated with deranged electrolytes. Electrolytes were seen to be initially deranged in the case we have reported as well. Respiratory compromise is also one of the complications faced by such patients due to restriction of the chest wall by the thick skin barrier. In patients who survive, the hyperkeratotic scale is shed in the initial few months, leaving erythematous skin covering the body [1]. Respiratory distress became the eventual cause of death in the case we hereby report. Studies have shown that mutations in the ABCA12 gene encoding a protein for lipid transport in the skin are involved in the pathogenesis of the disease. The ABCA12 gene encodes a protein involved in lipid transport across the epidermis of the skin. In harlequin ichthyosis, the transfer of lipid from the cytosol to the lamellar granules is absent [6]. The abnormality in the lamellar granules results in defective skin
Downloaded from http://tropej.oxfordjournals.org/ at Warsaw University on January 16, 2015
Fig. 1. A newborn showing the signs of Harlequin ichthyosis.
feeding was started on the second day of life and was tolerated well by the patient. Electrolytes returned to normal on the third day of life. Scales had started to shed off and erythematous skin was visible. A discharge was evident on some parts of the plaques on the skin. The patient expired on the seventh day of life due to respiratory distress. A postmortem study could not be conducted due to consent reasons. There was a history of death of a prior sibling with same condition on the third day of life. The father of the baby was a 35-year-old suffering from eczema that pursued a chronic relapsing course. He had first reported his skin ailment 12 years ago and had approached various general practitioners and dermatologists for its treatment. The eczematous lesions mostly surrounded his ankles, knees and elbows. Currently, he was on oral steroid therapy that had been prescribed to him by a general practitioner in his neighborhood. The father also reported that one of his siblings had a similar skin disease as himself.
Harlequin Ichthyosis in an Infant Born to a Father with Eczema
3
Moreover, harlequin ichthyosis can be expected in babies who are product of consanguineous marriage, have eczema in one of the parents and display polyhydramnios on ultrasound in the third trimester of pregnancy. This will enable the pediatric units to be better equipped to deal with such a condition.
CONCLUSION The similarities in the pathogenesis of harlequin ichthyosis and eczema and the genetic mutation of filaggrin might suggest an association between the two conditions. Harlequin ichthyosis can hence be looked out for in infants of parents with eczema, especially when accompanied with abnormal ultrasonographic findings in the third trimester of pregnancy.
REFERENCES 1. Harvey HB, Shaw MG, Morrell DS. Perinatal management of harlequin ichthyosis: a case report and literature review. J Perinatol 2010;30:66–72. 2. Sohn A, Frankel A, Patel RV, et al. Eczema. Mt Sinai J Med 2011;78:730–9. 3. Sabin BR, Peters N, Peters AT. Chapter 20: atopic dermatitis. Allergy Asthma Proc 2012;33(Suppl. 1):S67–9. 4. Gurses D, Kilic I, Baskan M. A case of harlequin fetus with psoriasis in his family. Internet J Hematol 2000;1:1. 5. Rajpopat S, Moss C, Mellerio J, et al. Harlequin ichthyosis: a review of clinical and molecular findings in 45 cases. Arch Dermatol 2011;147:681–6. 6. Kelsell DP, Norgett EE, Unsworth H, et al. Mutations in ABCA12 underlie the severe congenital skin disease harlequin ichthyosis. Am J Hum Genet 2005;76:794–803. 7. Omidi AA, Katebi M, Ghannad Kafi SH, et al. Harlequin ichthyosis: a report of two cases. Iranian J Dermatol 2005; 8:54–6. 8. Habib A, Pasha W, Raza N, et al. Harlequin ichthyosis in two siblings. J Coll Physicians Surg Pak 2011;21:503–5. 9. Ring J, Mo¨hrenschlager M, Weidinger S. Molecular genetics of atopic eczema. Chem Immunol Allergy 2012;96: 24–9. 10. Thyssen JP, Godoy-Gijon E, Elias PM. Ichthyosis vulgaris: the filaggrin mutation disease. Br J Dermatol 2013;168: 1155–66. 11. Lakshmi C, Srinivas CR. Hand eczema: an update. Indian J Dermatol Venereol Leprol 2012;78:569–82.
Downloaded from http://tropej.oxfordjournals.org/ at Warsaw University on January 16, 2015
permeability and the complications associated with harlequin ichthyosis. Harlequin ichthyosis is associated with high morbidity and mortality [5]. However, the use of oral retinoids which aid in the shedding of the hyperkeratotic scale has given a hope for its management. In a study conducted by Rajpot et al. [5] on 45 cases of harlequin babies, 20 of the 24 patients (83%) who were given oral retinoids survived. With good palliative care, the survival rate in the overall 45 cases was more than 50%. Supportive therapy for such babies includes fluid and electrolyte management, humidification, prevention of infection, lubrication and prevention of desiccation of the eyes. Considering the predominant inheritance pattern of this disease, which is autosomal recessive, consanguinity is an important risk factor of this condition. There have been reports of siblings of consanguineous parents affected with this disorder [7, 8]. Skin diseases in parents have also been stated as a possible risk factor. A case of a father with psoriasis has been reported [4]. In our case the father of the baby was suffering from eczema. Genetic predisposition to eczema is associated with mutation in epidermal protein filaggrin on chromosome 1 [9]. This mutation is associated with defective epidermal barrier. The protein filaggrin is also vital in maintaining effective skin barrier. Mutations in the filaggrin gene are also associated with an autosomal dominant genetic disorder and a milder form of ichthyosis, hereditary ichthyosis vulgaris [10]. Ichthyosis vulgaris is associated with xerosis, scaling, hyperkeratosis and a relationship to atopic disorders. Oral retinoids also have a role in the treatment of chronic hand eczema [11]. As per our knowledge, there has been no reported case of a child with harlequin ichthyosis born to parents suffering from eczema. The similarities in the pathogenesis in the form of a defective epidermal barrier and the common gene mutation of filaggrin in a milder form of ichthyosis and eczema may imply a possible relationship between these two conditions. Eczema can emerge as a risk factor in parents for harlequin babies.
