PROF.DR. MAGESHKUMAR’S UNITDr.Aarthy.J

A CASE OF CHRONIC DIARRHEA

20 Year old young girl presented with,

• H/O loose stools- 4 weeks, watery, small volume, >10episodes/day, blood and mucus(+), associated with colicky, perumblical abdominal

pain present even on minimal food intake no tenesmus, malena no fecal incontinence

• H/O fever- 4 weeks, intermittent, low grade, no chills or rigor

• H/O weight loss (+)• H/O loss of appetite(+)

CHRONIC DIARRHEA Factitious ROME III Criteria(+) – IBS

Bloody diarrhea Watery diarrhea Steatorrhea

InflammatoryDiarrhea Osmotic Secretory diarrhea diarrhea

Causes of Chronic Diarrhea According to Predominant Pathophysiologic Mechanism

INFLAMMATORY CAUSES STEATORRHEAL CAUSES 1. Idiopathic inflammatory bowel disease 1. Intraluminal maldigestion (pancreatic exocrine

2. Infections insufficiency, bacterial overgrowth) 3. Radiation injury 2. Mucosal malabsorption (celiac sprue, Whipple's disease) 4. Gastrointestinal malignancies 5. Immune-related mucosal disease 3. Post-mucosal obstruction (1° or 2° lymphatic obstruction) ( primary and secondary immunodeficiency, food allergy)

SECRETORY CAUSES OSMOTIC CAUSES

1.Laxative abuse 1. Osmotic laxatives (Mg2+, PO4–3, SO4

–2) 2.Chronic ethanol ingestion 2. Lactase and other disaccharide deficiencies 3.Bowel resection, disease, or fistula 4.Partial bowel obstruction 5.Diabetic autonomic neuropathy DYSMOTILITY 6. Hormone-producing tumors 1.Irritable bowel syndrome (carcinoid, VIPoma, medullary cancer of thyroid, 2. Drugs (prokinetics) colorectal villous adenoma) 3.Hyperthyroidism 7.Addison's disease

• No H/O nausea, vomiting• No H/O hematemesis or malena• No H/O abdominal mass• No H/O steatorrhea• No H/O intermittent constipation• No H/O jaundice• No H/O skin rashes, pigmentation• No H/O joint pain• No H/O oral ulcers• No H/O wheezing, intermittent flushing• No H/O any neck swelling

• Past H/O: No H/O Diabetes mellitus, Tuberculosis, Thyroid disorders, Pelvic irradiation, Eating disordersNo H/O previous abdominal surgeries

• Drug H/O:No H/O chronic intake of laxatives, antacids, antibiotics, NSAIDS,

cardiac glycosidesNo H/O herbal therapy

• Family H/O: No H/O Tuberculosis No H/O similar illness

On examination, Patient conscious, oriented ill built emaciated dehydrated pale BP- 100/70 PR- 96/ min Temp- 98.4F

• CVS- S1 S2 (+), no murmur

• RS- B/L NVBS(+), no added sounds

• P/A- Scaphoid no scars, sinuses or dilated veins soft, no tenderness, no organomegaly no free fluid bowel sounds(+)P/R- no skin tags, ulcers, fissures or hemorrhoids

• PROBLEMS: 1.Chronic inflammatory diarrhea with

dehydration 2.Fever 3.Malnutrition 4.Anemia

Causes of Chronic Diarrhea According to Predominant Pathophysiologic Mechanism

INFLAMMATORY CAUSES STEATORRHEAL CAUSES Idiopathic inflammatory bowel disease Intraluminal maldigestion (pancreatic exocrine

Infections insufficiency, bacterial overgrowth) Radiation injury Mucosal malabsorption (celiac sprue, Whipple's disease) Gastrointestinal malignancies Immune-related mucosal disease Post-mucosal obstruction (1° or 2° lymphatic obstruction) ( primary and secondary immunodeficiency, food allergy)

SECRETORY CAUSES OSMOTIC CAUSES

Laxative abuse Osmotic laxatives (Mg2+, PO4–3, SO4

–2) Chronic ethanol ingestion Lactase and other disaccharide deficiencies Bowel resection, disease, or fistula Diabetic autonomic neuropathy Partial bowel obstruction DYSMOTILITY Hormone-producing tumors Irritable bowel ssyndrome (carcinoid, VIPoma, medullary cancer of thyroid, Drugs (prokinetics) colorectal villous adenoma) Hyperthyroidism Addison's disease

Differential diagnosis

• Immunodeficiency• Gastrointestinal infections Tuberculosis, Salmonella, Campylobacter Amoebiasis, Giardiasis, Strongylodosis, Cryptosporidiosis, Isospora• Inflammatory bowel disease• Gastrointestinal malignancy• Secretory diarrhea ( endocrinal origin)

APPROACH TO CHRONIC DIARRHEA

Bloody diarrhea Watery diarrhea Steatorrhea

Response to fasting Assess for SI/

Inflammatory Stool osmotic gap PancreaticDiarrhea Disease

Osmotic Secretory diarrhea diarrheaPathogen screen (-) Lactose breath test Pathogen screen (-) Endoscopy ColonoscopyColonoscopy Stool Mg2+/PO4 Sigmoidoscopy + biopsy Imaging n Hormonal assay

INVESTIGATIONS

• Hb- 12.9 RBS- 89mg%• TC- 6700 B. urea- 19mg%• DC- P57 L41 E3 Sr. creatinine- 0.7mg%• ESR- 5/12 Na- 131, K- 3.1, Cl- 104• PCV- 25 HCO3- 24• MCV- 73fl• MCH- 24pg CXR PA- normal• MCHC- 34g/dl ECG- NSR/ WNL• PLT- 1.3 lakhs/cumm

• LFT- normal range• TFT- normal range• HIV ELISA- non reactive• Stool ova cyst- nil• Stool occult blood- positive• USG abdomen and pelvis- Paraortic area obscured No other significant abnormality

TREATMENT

• IVF• Inj. Ciprofloxacin• Inj. Metronidazole• Inj.Ranitidine• C. Bifilac• T.Paracetamol

• Pt condition didn’t show any drastic improvement.

DIFFERENTIAL DIAGNOSIS

• Gastrointestinal infections 1.Tuberculosis, Campylobacter, Salmonella,

Aeromonas, Plesiomonas

• Inflammatory bowel disease• Gastrointestinal malignancy• Secretory diarrhea (endocrinal origin)

• MGE opinion obtained. Suggested: 1.Colonoscopy 2.CECT abdomen• Mantoux test- negative

• Colonoscopy- normal• Endoscopy-

Tender gastric erosions, deformed duodenal bulb and pylorus

D1- D3 – mucosa granulomatous, edema(+) with nodules and loss of mucosal folds

Biopsy done from D3

• CECT abdomen-Thickening and nodularity noted in third part of

duodenum with multiple paraortic and periduodenal nodes with few nodules in the greater omentum and body of stomach

DDUODENAL BIOPSY

• Duodenal biopsy- Showed duodenal mucosa with

superficial erosions. Lamina propria shows monotonous sheets of mononuclear cells with focal aggregates of large cells with vesicular chromatin and prominent nucleoli. Also seen are few congested vessels.

Features suggestive of Diffuse large B cell Lymphoma of duodenum

Medical oncologist opinion sought.Suggested

1.Immunohistochemistry- CD19, CD20 (+)

2.Serum LDH- 10703.Serum calcium- 9.2mg/dl

4.Serum uric acid- 4.5mg/dl5.CECT Chest- No significant abnormality6. Bone marrow aspiration- normal study

Patient was started on CHOP regimen

• FINAL DIAGNOSIS:Primary DIFFUSE LARGE B CELL LYMPHOMA OF

DUODENUM AND STOMACHAnatomical Ann Arbor stage :STAGE IIIPI staging : 2 risk factor present

( INTERMEDIATE RISK )

LYMPHOMA OF SMALL INTESTINE

• Small-bowel tumors comprise <3% of gastrointestinal neoplasms

• Lymphomas of the small intestine are the second most common malignancy of the small bowel

• Lymphoma in the small bowel may be primary or secondary

• Secondary lymphoma of the small bowel consists of involvement of the intestine by a lymphoid malignancy extending from involved retroperitoneal or mesenteric lymph nodes

PRIMARY INTESTINAL LYMPHOMA

• Primary intestinal lymphoma accounts for ~20% of malignancies of the small bowel.

• These neoplasms are non-Hodgkin's lymphomas; they usually have a diffuse, large-cell histology.

• Intestinal lymphoma involves the ileum, jejunum, and duodenum, in decreasing frequency.

• The risk of small-bowel lymphoma is increased in patients with a prior history of malabsorptive conditions (e.g., celiac sprue), regional enteritis, and depressed immune function

• Symptoms: Periumbilical pain (made worse by eating) as well

as weight loss, vomiting, and occasional intestinal obstruction.

• The diagnosis of small-bowel lymphoma may be suspected from the appearance on contrast radiographs of patterns such as infiltration and thickening of mucosal folds, mucosal nodules, areas of irregular ulceration, or stasis of contrast material.

• Confirmed by endoscopy and biopsy

ANN ARBOR STAGINGSTAGE FEATURE

I Involvement of a single lymph node region or lymphoid structure (e.g., spleen, thymus, Waldeyer's ring)

II Involvement of two or more lymph node regions on the same side of the diaphragm

III Involvement of lymph node regions or lymphoid structures on both sides of the diaphragm

IV Involvement of extranodal site(s) beyond that designated as "E“ More than one extranodal deposit at any location Any involvement of liver or bone marrow

A No symptoms

B -Unexplained weight loss of >10% of the body weight during the 6 months before staging investigation-Unexplained, persistent, or recurrent fever with temperatures >38°C during the previous month-Recurrent drenching night sweats during the previous month

E Localized, solitary involvement of extralymphatic tissue, excluding liver and bone marrow

INTERNATIONAL PROGNOSTIC INDEX FOR NHL

Five clinical risk factors:• Age 60 years• Serum lactate dehydrogenase levels elevated• Performance status >2 (ECOG) or <70

(Karnofsky)• Ann Arbor stage III or IV• >1 site of extranodal involvement

• 0-1: Low risk 2-3: intermediate 4-5: High risk

• Resection of the tumor constitutes the initial treatment modality.

• While postoperative radiation therapy has been given to some patients following a total resection, most authorities favor short-term (three cycles) systemic treatment with combination chemotherapy.

• The frequent presence of widespread intraabdominal disease at the time of diagnosis and the occasional multicentricity of the tumor often make a total resection impossible.

• The probability of sustained remission or cure is ~75% in patients with localized disease but is ~25% in individuals with unresectable lymphoma.

CHARACTERISTICS OF COMMON TYPES OF NHL INVOLVING GIT

TYPE OF NHL Extranodal marginal zone B cell of MALT type

Diffuse large B cell

Peripheral T cell Burkitt

Gastrointestinal involvement %

50 18 15 11

Median Age, years

60 64 61 34

Stage I/II vs III/Iv 67 vs 33 54 vs 46 20 vs 80 62 vs 38

B symptoms % 19 33 50 22

Bone marrow involvement %

14 16 36 33

Chemotherapyregimen

Chlorambucil CHOP/ R CHOP CHOP CHOP

% surviving 5 years

74 46 25 45

CHARACTERISTICS OF COMMON TYPES OF NHL INVOLVING GIT

TYPE OF NHL Extranodal marginal zone B cell of MALT type

Diffuse large B cell

Peripheral T cell Burkitt

Gastrointestinal involvement %

50 18 15 11

Median Age, years

60 64 61 34

Stage I/II vs III/Iv 67 vs 33 54 vs 46 20 vs 80 62 vs 38

B symptoms % 19 33 50 22

Bone marrow involvement %

14 16 36 33

Chemotherapyregimen

Chlorambucil CHOP/ R CHOP CHOP CHOP

% surviving 5 years

74 46 25 45

CHARACTERISTICS OF COMMON TYPES OF NHL INVOLVING GIT

TYPE OF NHL Extranodal marginal zone B cell of MALT type

Diffuse large B cell

Peripheral T cell Burkitt

Gastrointestinal involvement %

50 18 15 11

Median Age, years

60 64 61 34

Stage I/II vs III/Iv 67 vs 33 54 vs 46 20 vs 80 62 vs 38

B symptoms % 19 33 50 22

Bone marrow involvement %

14 16 36 33

Chemotherapyregimen

Chlorambucil CHOP/ R CHOP CHOP CHOP

% surviving 5 years

74 46 25 45

CHARACTERISTICS OF COMMON TYPES OF NHL INVOLVING GIT

TYPE OF NHL Extranodal marginal zone B cell of MALT type

Diffuse large B cell

Peripheral T cell Burkitt

Gastrointestinal involvement %

50 18 15 11

Median Age, years

60 64 61 34

Stage I/II vs III/Iv 67 vs 33 54 vs 46 20 vs 80 62 vs 38

B symptoms % 19 33 50 22

Bone marrow involvement %

14 16 36 33

Chemotherapyregimen

Chlorambucil CHOP/ R CHOP CHOP CHOP

% surviving 5 years

74 46 25 45

IMMUNOPROLIFERATIVE SMALL INTESTINAL DISEASE (IPSID)

• Small-bowel B cell lymphoma, diffusely involving the entire intestine

• Presents with chronic diarrhea and steatorrhea, vomiting and abdominal cramps; clubbing of the digits(+)

• Presence in the blood and intestinal secretions of an abnormal IgA that contains a shortened -heavy chain and is devoid of light chains

• Good clinical improvement when antibiotics and chemotherapy are combined.

REFERENCES:

• Harrison’s Principles of Internal Medicine, 17th edition

• Washington Manual of Medical Therapeutics, 32nd edition

• Web references from medscape