Henry Ford Hospital Medical Journal

Volume 18 | Number 1 Article 10

3-1970 Intestinal Lymphagiectasia with Normal Immunological Function: A Case Report T. Madhavan

C. E. Rupe

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Recommended Citation Madhavan, T. and Rupe, C. E. (1970) "Intestinal Lymphagiectasia with Normal Immunological Function: A Case Report," Henry Ford Hospital Medical Journal : Vol. 18 : No. 1 , 65-72. Available at: https://scholarlycommons.henryford.com/hfhmedjournal/vol18/iss1/10

This Article is brought to you for free and open access by Henry Ford Health System Scholarly Commons. It has been accepted for inclusion in Henry Ford Hospital Medical Journal by an authorized editor of Henry Ford Health System Scholarly Commons. Henry Ford Hosp. Med. Journal Vol. 18, No. 1, 1970

Intestinal Lymphagiectasia with Normal Immunological Function

A Case Report

T. Madhavan, M.D.* and C. E. Rupe, M.D.**

A patient is reported with histologically proven intestinal lymphangiectasia and protein losing enteropathy. The gastrointestinal protein loss and the effect of low diet have been demonstrated. The morphological abnormalities with radio­ logical and lymphangiographic findings are discussed. Immunological studies are analyzed. These patients may have normal function both humoral and cellular, in spite of fairly advanced disease. Also the new hereto unreported association of Graves' Disease arid intestinal lymphangiectasia has been brought out.

The syndrome of lymphangiectasia ization at that time (June, 1966), all the with hypercatabolic protein loss was pertinent laboratory findings were normal except for a total protein of 6.2 gm/100 cc; first described in 1961 by Waldmann an albumin of 3.68 gm/100 cc; aiglobulin et al, who reported a group of 12 pa­ 0.39 gm/lOOcc; a^globuUn 0.67 gm/100 tients with and exuda­ cc, and gamma 0.84 gm/100 cc. A diagnosis of hyperthyroidism was made tion of proteins into the gastrointestinal on the basis of clinical symptoms, presence tract. 1 The pathologic findings in the of diffuse goiter, protein-bound iodine of 10.9 /ig/100 cc and 24-hour radioiodine up­ showed pronounced di­ take of 71%. Following treatment with latation of the lymphatics of the mu­ Tapazole 10 mg q.i.d. for eight months, cosa and submucosa, 1 and chylous ef- there was remission of the disease. fusions.2'^ Introduction of newer tech­ The patient was readmitted in May 1967 with involving axillary, nics (including Cr^^ labelled albumin, posterior cervical, supratrochlear and in­ 1131 labelled Polyvinyl pyrrolidone and guinal nodes which were discrete, hard and 1181 labelled serum proteins )i has en­ slightly tender. He also had a palpable liver about 9 cms below the right costal margin. abled the detection and quantitation of Laboratory findings were negative. of this protein loss.*-^ Immunological in­ the right axillary node was reported as "re­ vestigations have also thrown light on active hyperplasia." The serum protein pat­ tern was essentially unchanged from that of the immunological aspects of this dis­ previous admission. A chest x-ray revealed ease. a small, left . Over the en­ suing months the became more fre­ Report of a Case quent and severe gradually involving the A 36-year-old white male was admitted to thoracic and abdominal serous cavities with Henry Ford Hospital for the third time on attendant symptoms of dyspnea, abdominal April 20, 1969, with an illness dating back distension and pedal edema. The patient three years when transient, intermittent pedal formerly smoked one pack of cigarettes a edema had first appeared. During hospital- day. He had never been jaundiced; bowel habits were regular, although stools were occasionally frothy and floating. There was *Department of Medicine no family history of chronic and debilitating ''•Fourth Medical Division disorders.

65 Madhavan and Rupe

Physical examination revealed a well- tolerance test for intestinal developed, thin white male, not in acute revealed no defect in pentose absorption. distress but slightly dyspneic. The blood Lupus erythematosus preparations and anti­ nuclear factors were negative. The electro­ pressure was 136/86 mm Hg, pulse 90/min cardiogram revealed low voltage and poor and temperature was normal Integumental progression of R-waves in Vi-.-,. changes consisted of thickening and ridging of fingernails. Small lymph nodes were pal- A biopsy of the right inguinal node Table I performed on April 24, 1969, showed Serum Protein Determinations chronic lymphadenitis. On June 5, T. P. Albumin - 1 - 2 Betascites with no hepatospleno­ megaly. Deep pitting edema of the feet, of Furosemide daily and subsequently ankles and pretibial areas was present. All discharged. other findings were normal. X-ray films of On June 1. 1969, he was readmitted the chest showed moderate pleural effusions on both sides. An esophagram revealed mini­ mal motor abnormality with a small hiatal hernia. Barium studies of the upper gastro­ intestinal tract revealed a retroperitoneal mass, probably lymph nodes, pressing on the duodenal loop, possibly with some invasion and infiltration. A small bowel series was compatible with a diffuse infiltrative process, such as lymphoma. The hemoglobin was 15.6 gm/100 cc. There was mild ranging from 10200-16900/cu mm with per­ sistent lymphopenia ranging from 2% to 13%, but on one occasion were 28%. Peripheral smear was normal. Bone morrow studies showed an increased myeloid: erythroid ratio (4.8 to 1). PDD and cocci­ dioidomycosis skin tests were negative. Skin tests for monilia (12 mm), mumps (18 mm) and (14 mm) were positive. The pleural fluid analysis revealed protein of 3.8 gm/100 cc and specific gravity of 1025. Cultures were negative. The serum al­ bumin concentration was 3.6 gm/100 cc with a total protein of 6.2 gm/100 cc on admis­ sion but became progressively lower, drop­ ping to 1.77 gm/100 cc with a total protein Figure 1 of 4.3 gm/100 cc on 6/12/69 (Table I). Serum carotene was 59 mcg%. A xylose Hypoplastic lymphatic vessels below the knee.

66 Intestinal Lymphangiectasia with Normal Immunological Function

Figure 2 Lymphangiogram demonstrating the dermal backflow.

for laparotomy. Pleural effusions re­ quired repeated aspirations before the operation. The fluid was clear and straw colored. On June 16, 1969, laparotomy was performed under gen­ eral anesthesia. In the peritoneal cavity 2200 cc of thick chylous ascites was encountered. The upper jejunum was grossly edematous with dilated lym­ phatic channels. There was milky staining of the mesenteric border of the upper jejunum with visible oozing of the milky fluid at this level (Fig 4). There were numerous tiny elevations which appeared to be lymphatic telan­ giectasia in the upper two feet of the jejunum but not in the upper ileum. The anterior mesentery of the small bowel, particularly the upper jejunum, was grossly thickened and rubbery with dilated lymphatics. Histopathological studies of the appendix, a mesenteric and a segment of liver were normal. A yellowish-tan segment Figure 3 of small intestine which included mu­ cosa and submucosa from two levels of The femoral and inguinal lymph nodes en­ larged with less uptake of the dye the ileum exuded a milky fluid when

67 Madhavan and Rupe

tained with oil red O and osmic acid on unfixed frozen sections. No stain­ ing was observed with periodic acid Schiff or alcian blue stains. Several groups of large mononuclear cells with finely vacuolated cytoplasm containing oil red O positive lipid were found in the submucosa and mu- Table III

Enteric Virus Neut. Antibody Tilers: I IqG Quality and Quantity) (Norinai: 1:16) Polio Coxsackie Echo (1) 111) (111) IA9) IBU IBZ) 163) IB4) (B5) 161 19) (W)

S'l Sb 6/23/69 16 32 32 < 8 256 NS 128 - 16 -16 16 Sc 7/01/69 32 6« 64 8 256 32 ? 256 - 32 8 16 Herpes Group H. Simplex H. Zoster Cytomeqaio Heteroohile CRP Sa 4/26/69 - Neg. Sa, 6/0718) Sb 6/23/69 Neg. 0.3 mg% Sc 7/01/69 64 Neg. 0.6 lttg% cosa and sometime within lymphatics (Fig 6). Only scattered smafl lympho­ Figure 4 cytes and plasma cells were seen in Small bowel showing the grossly edematous anterior jejunum with dilated lymphatic the mucosa, with no lymphoid nodules channels and milky staining of the mesen­ observed in the sections studied. Treat­ teric border. ment with Furosemide was continued postoperatively. A low fat diet yielded transected. Numerous single and some improvement in the serum al­ grouped dilated, sometimes coalescing, bumin which rose from 1.77 gm/100 endothelial lined spaces were found in cc to 2.82 gm/100 cc. A dose of 50 the broad folds of the mucosa and to a microcuries of Cr^'^ was injected intra­ lesser extent in the submucosa (Fig 5). venously on June 23 and stools col­ These were interpreted as lymphatics. lected for the next 92 hours showed the Some of the lumens contained a homo­ Cr'i level to be 9.3%. Normal Cr" geneous, lightly eosin-stained material, level is less than 1 %. The patient was a few mononuclear cells and vacuoles discharged on June 27. of varying size. Weak to moderate Both humoral and cytological im­ staining of the luminal material was ob- mune responses were studied pre- and Table IT post-operatively. Serum immunoglobu­ lins were determined quantitatively by Serum Immunoglobulins micro-double diffusion in agar technic IgG IgA IgM and found to be normal or low normal. (600-1400) (30-135) (40-120) Results are shown in Table II. Serum 4/26/69 554 97 4^ complement was within the normal 6/23/69 544 147 52 range, as was the beta Ic/IA globulin 7/01/69 776 177 31 on two different occasions. Heterophile

6K Intestinal Lymphangiectasia with Normal Immunological Function

Figure 5 Numerous empty and filled dilated lymphatics are present principally in the mucosa producing widened blunted muscosal folds. H and E X35 titers were negative and CRP was frequently asymmetrical edema, mild normal. Enteric virus neutralizing anti­ gastrointestinal symptoms and general­ body titers were also normal (Table ized disorders of lymphatic channels III). Skin windows using Dr. Rebuck's including dilated telangiectatic lympha­ technic and diphtheria toxoid^" re­ tic vessels of the submucosa of the vealed an early neutrophilic response small bowel. The immunologic phe­ (3 hrs), followed by a moderate num­ nomena associated with this syn­ ber of monocytes (6 hrs and 9 hrs) drome include hypogammaglobuline­ and later a small number of lympho­ mia, lymphocytopenia and impared cytes (12, 14 and 24 hrs). OveraU homograft rejection. The 9.3% fecal inflammatory response was below nor­ loss of intravenously injected Cr^^ es­ mal limits. tablishes that our patient had loss of Ten cultures utilizing serum proteins thru the gastrointestinal the patient's lymphocytes were studied. tract. There was slight increase in the Peripheral lymphocytes stimulated by amount of after dietary pokeweed mitogen in tissue culture fat restriction as noted in previous produced a 34-fold increase in tritiated studies.**"^ thymide uptake, compared to control Roentgenograms of the small bowel cultures. revealed coarsening of the folds, most Discussion pronounced in the jejunal area, separa­ Intestinal lymphangiectasia is the tion of the loops with suggestion of most common and most recently recog­ bowel wall thickening, compatible with nized protein-losing enteropathy char­ diffuse infiltrative process. These find­ acterized by early onset of massive, ings are consistent with previously re-

69 Madhavan and Rupe

A.

Figure 6 Details of the lymphatics, some of which contain vacuolated macrophages (A), and mucosal distortion are noted here. H and E X115

ported cases of intestinal lymphangiec­ as well as several large supraclavicular tasia.'* lymph nodes. Pomerantz and Waldmann reported Another case reported by McGuigan the lower extremity lymphangiograms et al demonstrated dilatation of the on four patients with this syndrome.® lacteals with normal appearance of the Three patients exhibited hypoplasia of retroperitoneal .^" It the lower extremity lymphatics. The was assumed that there was accom­ fourth patient had agenesis of the in­ panying congenital atresia of the guinal, pelvic and retroperitoneal lymphatic vessels draining the hands lymph nodes. This patient also demon­ and wrists. Our patient showed similar strated a tortuous double thoracic duct peripheral lymphatic findings: hypop-

70 Intestinal Lymphangiectasia with Normal Immunological Function lastic lower lymph vessels with obstruc­ IgG) were found to be normal or low tion and dermal backflow below the normal. These patients also exhibit knee. Also he had significant enlarge­ slightly impaired circulating antibody ments of groups of lymph nodes with response. Here again our patient's viral no specific histologic pattern. This sup­ neutralizing antibody titers were within ports the view that this is part of a normal range. The isolated elevation of generalized disorder of the lymphatic herpes simplex titer of 64 could rep­ system." resent subclinical viral infection during A laparotomy was required to dem­ the postoperative period. onstrate the hallmark lesion of this Lymphocytopenia is consistent with disease: edematous jejunum with di­ the previously reported cases. Anergy lated lymphatic channels and milky and impaired homograft rejection in staining of the intestine. This was later patients with intestinal lymphangie­ substantiated by histopathology. ctasia have suggested a deficiency of The occurrence of intestinal lymph­ lymphocyte-mediated immune respon­ angiectasia in four of seven cases of siveness. Our patient exhibited a posi­ nephrotic syndrome was reported re­ tive response to monilia and mimips cendy from Portugal. 12 Also a malab­ antigens. The delayed hypersensitivity sorption syndrome has been reported was also subsequently demonstrated in by Dobbins consisting of congenital the skin windows but with lesser num­ beta lipoprotein deficiency and intes­ ber of lymphocytes. Lymphocytes from tinal lymphangiectasia.The associa­ our patient's blood, though reduced in tion of hyperthyroidism and intestinal number, were capable of responding to lymphangiectasia in our patient is un­ mitogenic stimulation. There appears usual and the relationship between the to be no demonstrable cellular defect two is yet to be evaluated. of lymphocyte function. This correlates In a review of immunological func­ very well with McGuigan's observa­ tions of 18 patients with this disease, tions. Strober et al clearly demonstrated that these patients have gready reduced Acknowledgement serum concentration and total body Authors wish to thank Drs. John W. pool of each immunoglobulin, i* Rebuck, Lawrence C. Sweet, Gerald Surprisingly in our patient aU the Fine and Gerald Lo Grippo for their three immunoglobulins (IgA, IgM, and help and guidance in preparing this report.

REFERENCES

1. Waldmann, T. A., et al: The role of the gastrointestinal system in "idiopathic hypo­ proteinemia." Gastroenterology 41:197-207, Sept 1961. 2. Stoelinga, G. B. A.; Van Munster, P. J. J., and Slooff, J. P.: Chylous effusions into the intestine in a patient with protein-losing gastroenteropathy. Pediatrics 31:1011-8, Jun 1963. 3. Fadell, J. E.; Dame, R. W., and Wolford, J. L.: Chronic hypoalbuminemia and edema associated with intestinal lymphangiectasia. JAMA 194:917-8, 22 Nov 1965.

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4. Waldmann, T. A.: Protein4osing enteropathy. Gastroenterology 50:422-43, Mar 1966. 5. Waldmann, T. A.: Gastrointestinal protein loss demonstrated by ^'Cr-labelled albumin. Lancet 2:121-3, 15 Jul 1961. 6. Yissing, M.; Jensen, H., and Jarnum, S.: Dietary treatment of protein-losing enteropathy. Acta Paediat Scand 56:173-81, Mar 1967. 7. Holt, P. R.: Dietary treatment of protein loss in intestinal lymphangiectasia. Pediatrics 34:629-35, Nov 1964. 8. Jeffries, G. H.; Chapman, A., and Sleisenger, M. H.: Low-fat diet in intestinal lymph­ angiectasia. Its effect on albumin metabolism. New Eng J Med 270:761-6, 9 Apr 1964. 9. Pomerantz, M., and Waldmann, T. A.: Systemic lymphatic abnormaUties associated with gastrointestinal protein loss secondary to intestinal lymphangiectasia. Gastroenter­ ology 45:703-11, Dec 1963. 10. McGuigan, J. E., et al: Studies of the immunologic defects associated with intestinal lymphangiectasia. Ann Intern Med 68:398-404, Feb 1968. 11. Bookstein, J. J.; French, A. B., and Pollard, H. M.: Protein-losing gastroenteropathy: Concepts derived from lymphangiography. Amer J Dig Dis 10:573-81, Jul 1965. 12. De Sousa, J. S., et al: Association of nephrotic syndrome with intestinal lymphangiectasia. Arch Dis Child 43:245-8, Apr 1968. 13. Dobbins, W. O. 3d.: Hypo-beta-lipoproteinemia and intestinal lymphangiectasia: A new syndrome of malabsorption and protein-losing enteropathy. Arch Intern Med 111: 31-8, Jul 1968. 14. Strober, W., et al: Intestinal lymphangiectasia: A protein-losing enteropathy with hypogammaglobulinemia, lymphocytopenia and impaired homograft rejection. J Clin Invest 46:1643-56, Oct 1967. 15. Rebuck, J. W.; Boyd, C. B., and Riddle, J. M.: Skin windows and the action of the reticuloendothelial system in man. Ann NY Acad Sci 88:30-42, 1960.

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