Sandbox:Riad

Historical perspective

Primary intestinal lymphangiectasia (Waldmann's disease) was first discovered by Waldmann T.A. in 1961 when he reported 18 cases of patients having edema with low serum albumin and gammaglobulin and proteins levels ''idiopathic hypercatabolic hypoproteinemia". Assessment using radio-labeled ¹³¹I-albumin resulted in low levels in those patients. In addition, small intestinal biopsies were examined under microscope revealing different degrees of lymphatic vessel dilatation.

Pathophysiology

Pathology

PIL develops as a result of dilatation of intestinal lymphatic vessels (lacteals) with leakage of their contents into the bowel lumen leading to hypoalbuminemia, hypogammaglobulinemia and lymphopenia. Hypoproteinemia leads to edema. It is a form of protein losing enteropathy.

Genetics

Genes involved in the pathogenesis of PIL includes VEGFR3, LYVE-1, PROX1 and FOXC2 that are abnormally expressed in patients with PIL.

Associated conditions

There are five syndromes that have been reported to be associated with PIL. These syndromes include: 

Turner syndrome

Noonan syndrome

von Recklinghausen disease

Klippel-Trenaunay syndrome

Hennekam syndrome

Gross pathology

The jejunal villi appear creamy yellowish or whitish due to the dilated lymphatics in the intestinal mucosa.

Microscopic Pathology

The most important histopathological characteristics of PIL are dilated intestinal lymphatic vessels and lacteal juice in the biopsies from duodenum, jejunum and ileum.

Differential diagnosis

PIL must be differentiated from the secondary causes that lead to intestinal lymphangiectasia such as intestinal tuberculosis, inflammatory bowel disease, intestinal lymphoma, constrictive pericarditis, sarcoidosis, systemic sclerosis, whipple disease, radiation and/or chemotherapy with retroperitoneal fibrosis , HIV-related enteropathyand celiac disease.

Signs and symptoms

The hallmark of PIL is pitting edema which usually affects lower limbs in moderate cases and face and external genitalia in severe cases. In some cases, it can extend to serous membranes causing pericardial effusion, pleural effusion and chylous ascitis. Rarely, it can cause anasarca.

Other symptoms include: - Diarrhea, steatorrhea and malabsorption syndrome

- Fatigue

- Abdominal pain

- Abdominal mass

- Immunodeficiency

- Vitamin D deficiency Leading to osteomalacia and convulsion

- Iron deficiency anemia

- Mechanical ileus

- Chylous reflux into skin

- Recurrent GI bleeding

- Children have growth retardation

Diagnosis

PIL is diagnosed by biopsy revealing dilated intestinal lymphatics.

Other laboratory findings in PIL include:

- Low albumin level

- Low immunoglobulin IgM, IgA and IgG levels

- CBC shows lymphopenia

- Elevated 24-hour α1-antitrypsin clearance in stool, which is an indication of degree of protein loss and disease severity Contrast lymphangiography

Treatment

There is no definitive treatment for PIL; the mainstay of therapy is a low fat high protein diet with medium-chain triglyceride oral supplementation and supplemental calcium and vitamins.

Other reported therapeutic options include:

- Tranexamic acid is used to increase immunoglobulins and lymphocyte count

- Surgery (segmental small bowel resection) for localized lesions

Some controversial therapeutic options include: steroids and octreotide

Complications

Complications that can develop in PIL as a result of immunodeficiency are:

- Malignant transformation (lymphoma)

- Skin warts

- Infections

Prognosis

PIL is is associated with significant morbidity and requires adherence to the dietary modification and oral supplements; otherwise. it would be associated with poor outcome and low quality of life. It can be fatal in some cases if anasarca or malignancy develop.