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Monday, August 21, 2006

Hemihypertrophy and primary small intestinal lymphangiectasia

Hemihypertrophy and primary small intestinal lymphangiectasia in incontinentia pigmenti achromians

Riyaz A, Riyaz Najeeba, Anoop P, Chandni B, Noushad KDepartments of Pediatrics, Medical College, Calicut, Kerala, India

Correspondence Address:"ARAKKAL", Chalappuram, Calicut - 673 002, Kerala State,


A rare occurrence of primary small intestinal lymphangiectasia in an 8-year-old girl with incontinentia pigmenti achromians is reported. In addition, she had right sided hemihypertrophy. Though intestinal lymphangiectasia is known to have a few syndromic associations, its co-existence in a child with incontinentia pigmenti achromians has not yet been reported in the literature. Hemihypertrophy is also extremely rare in the latter and only very few instances of an association between the two have been documented previously.

Incontinentia pigmenti achromians (IPA), also known as hypomelanosis of Ito, is a neurocutaneous syndrome. It is characterized by skin lesions similar to a negative image of that present in the classical form of incontinentia pigmenti described by Bloch and Sulzberger. In addition to dermatologic and oral manifestations, the nervous and musculoskeletal systems are involved to a varying extent.[1] Primary small intestinal lymphangiectasia (PSIL) has not so far been described to be associated with IPA. A girl with the classical features of IPA along with hemihypertrophy and PSIL is reported. An association between hemihypertrophy and IPA has very rarely been reported in the literature.[2],[3]

Case Report

An 8-year-old girl born of a non-consanguineous marriage was evaluated for abdominal pain and ascites of subacute onset. She had mild mental retardation with a history of generalized tonic clonic convulsions since two years of age. Characteristic hypopigmented patches and streaks of IPA were present over the trunk and extremities [Figure - 1]. The whole of the right side of her body was hypertrophied. There were no dysmorphic features or congenital malformations. Cardiovascular and neurologic examinations were unremarkable. There was no hepatosplenomegaly.

She had lymphopenia; her total leukocyte count (TLC) was 5400/mm3 with 16% lymphocytes. There was no albuminuria. The total serum protein level was 4.8 gm/dl with an albumin fraction of 1.9 gm/dl. Her serum lipid profile revealed cholesterol of 104 mg/dl and a triglyceride level of 38 mg/dl. Tests of liver function showed a serum bilirubin of 1.1 mg/dl with a conjugated fraction of 0.2 mg/dl, alkaline phosphatase of 155 U/L and alanine aminotransferase (ALT) of 36 U/L. She had a blood urea of 18 mg/dl and a serum creatinine of 0.6 mg/dl. An ultrasonogram (USG) of abdomen detected free fluid within the peritoneal cavity, normal echotexture of liver and a normal portal vein.

Abdominal paracentesis revealed chylous ascites with 3.1 gm/dl proteins. The serum ascites albumin gradient (SAAG) was 0.9. Light microscopic examination of stool revealed the presence of 10-15 lymphocytes per high power field (HPF). A barium meal follow-through showed prominent valvulae conniventes and thickened nodular mucosal folds with the characteristic stacked coin configuration well known in PSIL [Figure - 2].

Gastroduodenoscopy revealed scattered white spots over the duodenal mucosa, having a snow-flake appearance [Figure - 3]. Biopsy from these sites demonstrated villus injury with dilated lymphatics and marked lymphocytic inflammatory changes [Figure - 4]. Based on these findings, she was diagnosed to have PSIL. Skin biopsy from one of her hypopigmented patches showed normal histology. A genetic analysis of blood and skin fibroblasts revealed a normal pattern of chromosomes.She was put on a diet rich in proteins and low in fat content. In addition, medium chain triglyceride (MCT) supplementation was provided. A repeat full blood count two months later revealed a TLC of 6900/mm3 with 28% lymphocytes. Stool microscopy showed 5-7 lymphocytes per HPF. Her total serum protein had increased to 5.3 gm/dl, with an albumin fraction of 2.4 gm/dl. Abdominal USG detected only minimal free fluid in the peritoneal cavity. However, serum cholesterol and triglyceride levels continue to remain low, at values of 122 and 44 mg/dl respectively.


IPA was first described by Ito in 1952. The hallmark of this heterogeneous group of inherited disorders is the marble cake-like whorls and streaks of hypopigmentation.[4] The skin lesions are similar to a negative image of that present in the X-linked dominant incontinentia pigmenti.[5] The palms, soles and mucous membranes are usually spared.[6] This girl had the typical dermatological pattern of this disorder. Skin biopsy usually reveals normal histology, as in her case.[4]

The pattern of inheritance in IPA is diverse. Previous reports have identified many cases to be associated with chromosomal mosaicism.[7],[8] In a study on 41 pediatric cases over a period of 20 years, chromosomal anomalies were encountered in 3 children.[7] Another report by Ohashi et al described chromosomal mosaics in lymphocytes and skin fibroblasts in 5 out of 9 individuals with pigmentary dysplasias of skin.[8] However, a genetic analysis of the present case showed a normal chromosomal pattern.

Apart from skin manifestations, ocular anomalies like strabismus, epicanthal folds and myopia are well known associations. Ophthalmologic evaluation of the present case did not reveal any of these abnormalities. Nervous system involvement in the form of seizures, electroencephalogram abnormalities and mental retardation are common.[7] Generalized tonic clonic seizures were encountered in this girl as well. In addition, she also had mild mental retardation. Musculoskeletal asymmetry is another common association - hemiatrophy has been reported in many patients. However this girl had hemihypertrophy of right side, which has very rarely been documented in IPA. A thorough search of the literature revealed only very rare reports of an association between the two.[2],[3]

The chylous ascitic fluid in the presence of a normal cardiac, hepatic and renal status pointed towards a possible lymphatic etiology. The diagnosis of PSIL seemed highly probable on barium contrast radiographs. An esophago-gastro-duodenoscopy with biopsy clinched the diagnosis.

Intestinal lymphangiectasia is a disorder that impairs lymphatic flow from the intestine, resulting in excessive enteric loss of plasma proteins.[9] Its symptoms and signs range from abdominal pain to hypoproteinemic edema and chylous ascites.[10] The presence of stool lymphocytes, lymphopenia, hypoalbuminemia and hypolipidemia are strong pointers towards a diagnosis of PSIL, as in the present case.

An endoscopy and histological study confirms the diagnosis. The duodenal mucosa may show scattered white spots having a snowflake-like appearance. Under a dissecting microscope, milky white substances are seen in the stroma of the villi. A high fat meal during the evening before endoscopic evaluation may make the diagnosis more apparent.[11] Small bowel contrast studies show thickened nodular mucosal folds that simulate the stacking of coins.[10] All these confirmatory tests showed the typical features of PSIL in this patient also.

An association between these two seemingly unrelated disorders could not be located in the literature. PSIL is known to occur in families.[12] De Sousa et al described intestinal lymphangiectasia in four out of seven intestinal biopsies performed on children with nephrotic syndrome.[13] A few genetic associations have also been recorded, the most striking being a patient with Noonan syndrome.[14] But whether PSIL actually was present remains a debatable point, as the same patient also had complex heart disease with right sided cardiac failure, which can very well result in secondary intestinal lymphangiectasia. Haddad and Wilkins found an association with a case of Turner syndrome.[15] In the present case, the association of various types of focal lesions, namely hemihypertrophy, pigmentary anomalies and lymphangiectasia strongly suggests the possibility of somatic mosaicism or a genetic mutation.

Dietary modification is the mainstay of management of such children. A high protein low fat diet with MCT supplementation (C 6:0 to C 12:0) is the standard recommendation.[16] The rationale is that MCT directly enters the portal venous system, bypassing the intestinal lymphatics. This modality of treatment was tried in our patient as well. Varying degrees of success have been described, ranging from partial reversal of lymphopenia to complete correction of the blood profile. The parameters which showed improvement with therapy in the present case were serum total protein, albumin and absolute lymphocyte count. A reduction in the volume of ascitic fluid and the number of stool lymphocytes were also noted.

The authors report this girl with the typical features of IPA and PSIL on account of the extreme rarity of such an association. The embryonic origin of epidermal and lymphatic tissues is diverse. The former arises from the ectoderm whereas the latter is mesodermal in origin. Hence a derangement in embryogenesis seems to be an unlikely etiology for the co-existence of IPA and PSIL in this girl. Her hemihypertrophy may well be an incidental finding, partially attributable to lymphedema. In any event, it may be of some benefit to strongly consider the rare entity of PSIL in the differential diagnosis of edema in a child with IPA. The report also re-emphasizes the benefits of dietary modification in such children and the limited role for drug therapy.


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Indian Journal of Pediatrics


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