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Indian Journal of Dermatology, Venereology and Leprology
Medknow Publications on behalf of The Indian Association of Dermatologists, Venereologists and Leprologists (IADVL)
ISSN: 0378-6323 EISSN: 0973-3922
Vol. 71, Num. 2, 2005, pp. 119-121
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Indian Journal of Dermatology, Venereology, Leprology, Vol. 71, No. 2, March-April, 2005, pp. 119-121
Case Report
Alagille syndrome with prominent skin manifestations
Sengupta Sujata, Das Jayanta Kumar, Gangopadhyay
Asok
Department of Dermatology, RKM Seva Pratisthan and Vivekananda Institute of Medical Sciences, Kolkata
Correspondence Address: UV-24/3C, Udayan, 1050/1, Survey Park,
Kolkata - 700075, West Bengal
senguptasujata@yahoo.co.in
Code Number: dv05037
ABSTRACT
Alagille syndrome, a rare genetic disorder with autosomal dominant transmission,
manifests 5 major features: paucity of interlobular bile ducts, characteristic
facies, posterior embryotoxon, vertebral defects and peripheral pulmonic
stenosis. We report a 6-year-old male child who presented with a history
of progressive jaundice since infancy, generalized pruritus and widespread
cutaneous xanthomata. He was also found to have obstructive jaundice,
pulmonary stenosis with ventricular septal defect and paucity of bile
ducts in liver biopsy. Histopathology confirmed skin lesions as xanthomata.
The child was diagnosed as a case of Alagille syndrome. This particular
syndrome with prominent cutaneous manifestations has been rarely reported
in the Indian literature.
INTRODUCTION
Genetic diseases affecting the skin sometimes pose a diagnostic dilemma for the treating physician. We report a child presenting with jaundice, pruritus and widespread xanthomata who was finally diagnosed as a case of Alagille syndrome (AS). AS or the syndromic paucity of bile ducts, consists of 5 major features comprising paucity of interlobular bile ducts, characteristic facies, posterior embryotoxon, vertebral defects and peripheral pulmonic stenosis.[1],[2] It is a rare genetic disorder with autosomal dominant transmission. The mutant gene has been localized to chromosome 20p.[3] This case is reported for the rarity of this entity; particularly in the Indian literature,[2] and to highlight the fact that early recognition of the skin lesions may play a role in the diagnosis of this disease.
CASE REPORT
A 6-year-old male child born of a non-consanguineous marriage presented
for evaluation of asymptomatic lesions over the face, hands and body
folds for the last 4 years. The child had been well till one month of
age after which he developed progressive jaundice. At the age of one-and-a-half,
he developed multiple raised non-itchy lesions over the knuckles, followed
by similar lesions on the eyelids, hands, and the body folds. The early
lesions were slowly growing and yellowish, but later they coalesced and
became skin-colored. There was associated pruritus that was generalized,
moderate to severe in intensity with no diurnal variation and not relieved
by treatment with oral antihistamines and topical calamine lotion and
steroids. The child′s developmental milestones were delayed. His
social smile had appeared at the age of 4 months and he was not able
to walk or talk till he was one-and-a-half years old. No sibling or any
other family member was similarly affected.
Cutaneous examination revealed asymptomatic well-defined painless, indurated
papules and plaques on the skin over the metacarpophalangeal and interphalangeal
joints of the hands, eyelids, and the axillary, antecubital, inguinal
and popliteal folds of both sides [Figure
- 1], [Figure
- 2] and [Figure
- 3]. Individual lesions tended to coalesce. Newer lesions were softer
and yellowish in color but older ones were mostly fibrotic and skin-colored.
The mucous membranes, palms and soles, hair, nails and teeth were normal.
On general examination, the child was stunted with a height of 101 cm
and weighing 14 kg. The face showed a broad forehead, deep-set eyes with
hypertelorism, and a pointed chin. Mild pallor and moderate icterus were
present and the vital signs were normal. A firm, non-tender hepatomegaly
was present. A pan-systolic murmur was audible over the precordium. The
rest of the systemic examination was normal.
On investigation, anemia, conjugated hyperbilirubinemia, raised SGPT,
alkaline phosphatase and GGT were detected. Serum cholesterol level was
413 mg/dl and triglyceride 257 mg/dl. HBsAg and anti-HCV antibody were
negative; chest X-ray was normal and abdominal ultrasound showed a heterogeneous
parenchymal echo pattern in the liver; echocardiography revealed a sub-aortic
VSD and severe pulmonary stenosis. Liver biopsy showed paucity of bile
ducts with the ratio of bile duct to portal triad, 0.66 (N=0.8). Ophthalmologic
and skeletal survey was normal. Skin biopsy of a new lesion showed small
and large aggregates of foam-cells [Figure
- 4]; another biopsy from a long-standing lesion revealed fibroblasts
and collagen bundles in large numbers. The child was diagnosed as a case
of Alagille syndrome.
DISCUSSION
Alagille syndrome (arteriohepatic dysplasia) is the syndrome of paucity
of intrahepatic bile ducts. It is probably inherited in an autosomal dominant
fashion with variable expression,[3] the
incidence being 1 in 100,000 live births.[4] The
disease is characterized by a peculiar facies, with abnormalities of the
liver, heart, eye, skeleton and kidney. Mild to moderate mental retardation
may be present. Subjects commonly present before 6 months of age for either
neonatal jaundice or cardiac murmurs; later they may present with poor
linear growth, with a broad forehead, pointed chin, deep-set eyes and elongated
nose with a bulbous tip. Hepatic disease is the key factor in AS and the
long-standing cholestasis and the resultant hypercholesterolemia cause
cutaneous manifestations of jaundice, pruritus, and widespread xanthomata.[3] Generalized
ecchymoses has also been reported as first clinical presentation.[1]
A study of 92 patients of AS showed paucity of interlobular bile ducts
in 85%, cholestasis in 96%, cardiac murmurs in 97%,
butterfly vertebra in 51%, posterior embryotoxon in the eye in 78% and
characteristic facies in 96%.[5] Our
case had three of the five major features of the syndrome with no vertebral
or ophthalmologic defects. This form of ′partial′ or ′incomplete′AS
has also been reported in the Indian literature by Shendge et al.[2] Bilateral
corneal opacity was found in an Indian girl with AS who also had mental
retardation, typical facies, cardiac murmur, xanthomatosis and cholestatic
jaundice.[7]
The long-term prognosis is uncertain with congenital heart disease, hepatic
cirrhosis, intracranial bleeding and renal abnormalities being the commonest
factors affecting mortality.[6] Pruritus,
often recalcitrant to medical therapy, has been reported to improve with
cholestyramine (12-15 g/day).[4] Hepatic
transplant is the surgical treatment of choice. The estimated 20-year survival
rates are 80% for those not requiring liver transplant and 60% for
those requiring it.[5] Rapid
resolution of widespread xanthomata has been reported in AS following orthotopic
liver transplant.[3]
Thus Alagille syndrome is a rare and grave systemic disorder that may be
diagnosed following the clues offered by methodical cutaneous examination.
REFERENCES
1. | Ukarapol N, Wongsawasdi L, Sittiwangkul R. A case report: Alagille syndrome. J Med Assoc Thai 2000;83:451-4. Back to cited text no. 1 |
2. | Shendge H, Tullu MS, Shenoy A, Chaturvedi R, Kamat JR, Khare M, et al. Alagille syndrome. Indian J Pediatr 2002;69:825-7. Back to cited text no. 2 |
3. | Buckley DA, Higgins EM, du Vivier AW. Resolution of xanthomas in Alagille syndrome after liver transplantation. Pediatr Dermatol 1998;15:199-202. Back to cited text no. 3 |
4. | Scheimann A. Alagille Syndrome, Emedicine. URL:http:// www.emedicine.com/ped/topic60.htm. Accessed on 13th August 2004. Back to cited text no. 4 |
5. | Emerick KM, Rand EB, Goldmuntz E, Krantz ID, Spinner NB, Piccoli DA. Features of Alagille syndrome in 92 patients: Frequency and relation to prognosis. Hepatology 1999;29:822-9. Back to cited text no. 5 |
6. | Hadchouel M. Alagille syndrome. Indian J Pediatr 2002;69;815-8. Back to cited text no. 6 |
7. | Nigale V, Trasi SS, Khopkar US, Wadhwa SL, Nadkarni NJ. Alagille Syndrome. A case report. Acta Derm Venereol 1990;70:521-3. Back to cited text no. 7 |
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