CT of abdomen: jejunal thickening and extensive lymphadenopathy

. Small bowel enteroscopy: areas of normal mucosa with patches of violaceous, fleshy, nodular, and friable mucosa

Hematoxylin and eosin stain of jejunal biopsy: spindle cell proliferation, extravasated red blood cells, plasma cell and lymphocyte infiltration

Immunohistochemical staining of jejunal biopsy: brown areas indicate immunoreactivity to HHV-8 antibody

Protein Losing Enteropathies

Morning ReportDeva Sharma, MD, MS

PGY32-25-2014

Pathogenesis of Protein-Losing Enteropathies:

• The GI tract normally does not contribute significantly to the catabolism of plasma proteins, accounting for only ~ 10% of the normal turnover of albumin and gamma globulin

• Mechanisms for increased intestinal leakage of plasma proteins:

• a.) Mucosal injury +/- erosions/ulcerations (ex- IBD & celiac disease)

• b.) Increased lymphatic pressure in the gut due to granulomatous or neoplastic involvement of the lymphatic system or after dilated lymph vessels leak protein via the surface epithelium into the gut

Pathogenesis of Protein-Losing Enteropathies:

• Unlike protein loss in glomerulopathies, leakage of serum proteins in enteropathies is independent of molecular weight

• Proteins with slower catabolic rates tend to be lost in the GI tract (albumin, IgA, IgM and IgG)

• Little change in concentration of serum proteins with a rapid turnover rate (insulin, IgE)

Causes of Protein Losing Enteropathy:

Inflammatory exudation due to mucosal erosions or ulcerations: a.) IBD b.) GI malignancy: - Gastric cancer- Lymphoma- Kaposi sarcoma- Alpha chain diseasec.) Clostridium difficile colitisd.) Erosive gastirits + ulceratione.) NSAID enteropathyf.) Post-chemotherapyg.) Cap polyposish.) Graft-vs-Host Disease

Intestinal loss of lymphatic fluid due to lymphatic obstruction: a.) 1° intestinal lymphangiectasiab.) R-sided heart failure- Constrictive pericarditis- Congenital heart

diseasec.) RP lymph node enlargementd.) Cirrhosis/portal hypertensive gastropathye.) Hepatic venous outflow obstructionf.) Enteric-lymphatic fistula

Increased permeability due to mucosal disease without erosions or ulcerations: a.) Celiac diseaseb.) Tropical spruec.) Giant hypertrophic gastritis (Menetrier’s dz)d.) Lymphocytic gastritise.) 2° hypertrophic gastropathyf.) Amyloidosisg.) Bacterial overgrowthh.) Acute viral infectioni.) Parasitic infectionj.) Whipple dieasek.) Rheum diseases (SLE, MCTD, RA)l.) Collagenous colitis

Protein Losing Enteropathies in the Immunocompromised Host:

CMV Enteritis

MAC

Lymphoma

Kaposi sarcoma

Clinical Manifestations and Lab Abnormalities in Patients with Protein Losing Enteropathies:

I. Clinical Manifestations: - Edema- Ascites- Pleural & pericardial effusions

II. Laboratory abnormalities: - Hypoalbuminemia without proteinuria, decreased

protein synthesis or malnutrition- Lymphopenia- Malabsorption of fat and fat soluble vitamins- Reduced plasma concentrations of:

- Gamma globulins- Cholesterol- Alpha-1 antitrypsin- Fibrinogen- Ceruloplasmin

III. Diagnosis using stool alpha-1 antitrypsin: -Can help to quantitate enteric protein loss-Has a higher molecular weight than albumin-Excreted intact in the stool (resistant to degradation in the intestinal lumen)-Does NOT distinguish b/w gastric and intestinal protein loss-Intestinal bleeding and diarrhea can also increase levels of stool alpha-1 antitrypsin

- Cl > 24 ml/day: pts w/o diarrhea- Cl 56 ml/day: pts with diarrhea

Kaposi Sarcoma Involving the GI Tract:

• Low-grade vascular tumor associated with HHV-8 infection• Most common GI malignancy seen in AIDS • Prior to the widespread introduction of HAART, the GI tract was

involved in 40% of patients with KS at initial diagnosis and up to 80% at atuopsy

• Often asymptomatic, but presenting symptoms can include: – GI bleeding– Abdominal pain– Weight loss– Nausea, vomiting– Malabsorption – Diarrhea

• Visceral involvement of KS can occur in the absence of cutaneous lesions, and is often associated with a poorer prognosis

• Treatment:– HAART (decreases formation of new lesions, improves survival)– Radiation therapy– Systemic chemo for disseminated disease (lisposomal doxorubicin is

first line)

A 29 year-old man is evaluated for newly diagnosed HIV infection. He has no symptoms and is willing to start combination antiretroviral therapy if necessary. He has no other medical problems and takes no medications. Physical exam is normal.

The CBC, serum chemistries and liver enzymes are normal. CD4 cell count is 424 / ul. HIV RNA viral load is 21,317 copies/ml. HIV resistance testing is negative for mutations. A hepatitis B virus surface antibody assay, serologic testing for syphilis, and a hepatitis C virus antibody assay are negative.

In addition to periodic follow-up monitoring, which of the following is the most appropriate management of this patient’s HIV infection?

(A) Begin combination antiretroviral therapy now(B) Withhold treatment until CD4 cell count falls below 350 / ul(C) Withhold treatment until HIV RNA viral load exceeds 55,000 copies /

ml(D) Withhold treatment until symptoms develop

A 29 year-old man is evaluated for newly diagnosed HIV infection. He has no symptoms and is willing to start combination antiretroviral therapy if necessary. He has no other medical problems and takes no medications. Physical exam is normal.

The CBC, serum chemistries and liver enzymes are normal. CD4 cell count is 424 / ul. HIV RNA viral load is 21,317 copies/ml. HIV resistance testing is negative for mutations. A hepatitis B virus surface antibody assay, serologic testing for syphilis, and a hepatitis C virus antibody assay are negative.

In addition to periodic follow-up monitoring, which of the following is the most appropriate management of this patient’s HIV infection?

(A)Begin combination antiretroviral therapy now(B) Withhold treatment until CD4 cell count falls below 350 / ul(C) Withhold treatment until HIV RNA viral load exceeds 55,000 copies /

ml(D) Withhold treatment until symptoms develop

Initiation of Antiretroviral Therapy:

• Department of Health and Human Services Guidelines / International AIDS Society U.S.A Panel:

• History of AIDS-defining opportunistic infection or malignancy

• Symptomatic HIV infection• CD4 cell count < 500/ul• Presence of HIV-associated nephropathy• Active co-infection with hepatitis B or C virus• Pregnancy, to prevent perinatal transmission• Pts at high risk for or already having cardiovascular disease,

regardless of CD4 cell count

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1:1353.• 4.Dansinger ML, Johnson S, Jansen PC, et al. Protein-losing enteropathy is associated with Clostridium difficile diarrhea but not

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• 9.Hendriksz CJ, McClean P, Henderson MJ, et al. Successful treatment of carbohydrate deficient glycoprotein syndrome type 1b with oral mannose. Arch Dis Child 2001; 85:339.

• 10.Kelly DG, Miller LJ, Malagelada JR, et al. Giant hypertrophic gastropathy (Ménétrier's disease): pharmacologic effects on protein leakage and mucosal ultrastructure. Gastroenterology 1982; 83:581.

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