H & P PRESENTATION5TH SEMESTER

Northside Medical Center

October 31st, 2013

Gagandeep Singh Anand (ganand@uwaterloo.ca)

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PATIENT INFORMATION

Patient Name: Ms. J. P. Age: 77 Sex: Female Ethnicity: Caucasian

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CHIEF COMPLAINT(S)

“Persistent diarrhea and pruned skin”

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HISTORY OF PRESENTING ILLNESS – 1/2 Ms. J is a pleasant 77 year-old female who presents with persistent diarrhea for 3 weeks, at 4-5 times/day. It is of watery consistency, brown color, foul smell, with traces of blood – though the patient reports of internal hemorrhoids as a possible reason – no mucus, and of undigested food.

The patient reports increased urge to void after consuming a meal and a coinciding BM with micturition, in addition, she reports of a progressively worsening frequency. She does not report of any active pain, but of slight lower abdominal discomfort for 15-20mins after a BM.

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HISTORY OF PRESENTING ILLNESS – 2/2 Ms. J reports of having a previous episode (2010) with

similar symptoms which was diagnosed as pseudomembranous colitis; she reports of no nausea, vomiting, sick contact or recent travel. Ms. J also reports of acute stress due to a sickness in the family.

She was prescribed Flagyl (metronidazole) for 10 days, for which she is on her 10th day. She was advised by her PCP to consume bananas and cheese to help with the diarrhea but had no improvement.

Ms. J reports having a dental procedure one month ago in which amoxicillin (4 tabs) was used.

She also stopped taking her monthly Simponi (Golimumab) injections for her RA because she believed it was the cause.

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PAST MEDICAL HX

Pseudomembranous colitis (2010) Fibromyalgia for 25+ years Rheumatoid arthritis (Type III hypersensitivity, anti-CCP+, HLA-DR4)

Psoriatic arthritis (RA affecting fingers and toes, HLA-B27)

HTN Internal hemorrhoids

COPD ( FEV1/FVC ratio)

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PAST SURGICAL HX

Laproscopic Cholecystectomy Dilation and curettage Joint surgery of left shoulder / knees BL / hips BL for RA

Intraocular lens (IOL) implants for cataracts in eyes BL (1993)

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FAMILY HX

Her mother (at 93) & father (at 83) both died of strokes.

Her son (57) recently had a stroke (July) and has a pacemaker.

She has an older sister (86) who had uterine cancer.

She also mentioned Irritable Bowel Syndrome present in the family.

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SOCIAL HX

Divorced, lives by herself in an apartment building and is “quite active”.

Drives and attends bible meetings on a weekly basis.

No 1st hand smoking – only history of extensive 2nd hand smoke through family.

No alcohol. No illicit drugs.

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MEDICATIONS & ALLERGIES

Medications

Diovan (valsartan) – 160mg daily AT II inhibitor

Protonix (pantoprazole) – 40mg daily R/O

inhibit H+/K+ ATPase in parietal cells

Simponi (golimumab) – 2 IM per month monoclonal Ab for TNFα

Heparin – tid activates antithrombin, thrombin & Xa

Allergies

Latex

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REVIEW OF SYSTEMS – 1/2

General: Denies fever, chills, sweats

HEENT: Occ. forehead aches, h/o head trauma on ice (4-5 yrs ago); denies visual changes or pain; had ear wax removed, denies hearing loss / tinnitus / vertigo / ear pain / discharge; reports some nasal drip, sinusitis; denies teeth problems / abnormal taste / sore throat / speech difficulty

Cardiopulmonary: Denies cough / dyspnea / wheezing / hemoptysis / chestpain / palpitations / orthopnea / PND / syncope

Gastrointestinal: Normal appetite, persistent diarrhea (4x/d), lower abdominal pain after BM (for 15-20min), h/o internal hemorrhoids

Genitourinary: Denies dysuria / discharge / nocturia. Watery BM coincides with micturition.

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REVIEW OF SYSTEMS – 2/2

Musculoskeletal: h/o RA, stiffness of left shoulder, denies stiffness of knees or hips.

Dermatological: Reports chancre sore on top lip after dental appointment (< 1 mo ago) – antiviral was prescribed. Reports prior pruning of skin, denies pruritus / rash / changes in hair

Neurological: Some moving pain, “maybe associated with the fibromyalgia”, denies seizures / paralysis / muscle weakness / cognitive complaints

Psychiatric: Some acute stress due to a family sickness (son had a stroke 1 month ago and is unable to work). Denies suffering from depression or anxiety other then that.

Endocrine: No history of thyroid problems or DM.

Hematology: Denies bleeding or clotting / easy bruising

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VITAL SIGNS

BP sitting: 114 / 70 Pulse Rate: 65 Pulse Rhythm: Regular Respirations: 16 Temp: 98.0 °F Height: 62” Weight: 140 lbs Pain: no acute active pain

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PHYSICAL EXAM – 1/2

General: AAOx3, very pleasant, NAD

HEENT: NC, AT; PERRLA, EOMI; hearing grossly intact, ø ear inflammation / discharge; patent nares, ø discharge / inflammation; ø gland enlargement / erythema / exudates

Mouth: Lips dry, mucosa moist, ø angular cheilitis, dentition intact and normal, ø mucosal / tongue lesions

Neck: supple, ø JVD / lymphadenopathy, trachea midline

Chest Wall: Symmetrical bilaterally, ø tenderness upon palpation

Breasts: Not performed

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PHYSICAL EXAM – 2/2

Lungs: CTA B/L, ø rhonchi / wheezing

Heart: S1/S2 +, RRR, murmur -

Abdomen: LLQ surgical scar, soft, NT, ND, BS + (in 4 quadrants), ø organomegaly, ø pain to superficial/deep palpation

Genitourinary: Not performed

Musculoskeletal: 3/5 ROM on left shoulder, ø acute pain, ø edema / clubbing / cyanosis. Radial pulse full and equal

Neurologic: CN 2-12 grossly intact

Skin: Warm & moist, ø gross lesions

Psychiatric: Patient’s affect is congruent with mood

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LABS / TESTS WBC: 4.5 5.5 x 103 per μL

Hb: 10.8 12.1 g/dL

Hct: 33.2%

PLTs: 159 x 103 per μL

Na+: 141 mEq/L

K+: 4.2 2.8 mEq/L

Cl-: 108 mEq/L

HCO3-: 27 mEq/L

BUN: 10 mg/dL

CR: 0.7 mg/dL

Glucose: 96 mg/dL

Lactic acid: 2.3 1.7 mEq/L

Ca2+: 8.2 mg/dL

Phosphate: 1.9 mg/dL

Amylase: 16 U/L

Lipase: 59 U/L

Alk. Phos.: 60 U/L

Albumin: 3.6 g/dL

ALT: 40 U/L

AST: 36 U/L

Bilirubin: 0.8 mg/dL

Mg+: 1.7 mEq/L

C. difficile Cx: Negative

Urine Analysis: Leukocyte Esterase: Positive

(25) WBC: Positive (5-10) Bacteria: Moderate

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ASSESSMENT / PLAN – 1/2

1.Persistent diarrhea: complete Flagyl dosage, re-send stool for WBC, Cx, ova & parasites.Continue 100 cc/hr IVFs to rehydrate and replenish electrolytes. Consider vancomycin. Consider endoscopy.

2.Lactic Acid Elevation: 1.7 2.3 mEq/L. Continue IVF’s.

3.Asymptomatic Bacteriuria: elevated LE, WBC & moderate bacteria. Denied urinary Sx on admission.

4.H/o Psoriatic arthritis: continue to see rheumatologist on OP basis, presently no medications.

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ASSESSMENT / PLAN – 2/2

5.H/o Fibromyalgia: no acute issues

6.H/o RA: consider holding Simponi injections if RA asymptomatic. Consult with specialist.

7.HTN: continue valsartan 160mg daily

8.H/o COPD: no acute issues

9.DVT prophylaxis: heparin tid

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DIFFERENTIAL DIAGNOSIS – 1/3 Pseudomembranous colitis (C. difficile) 2o to

antibiotic use Gram-positive obligate rod. Toxins bind brush border, destroy

cytoskeletal structure of enterocytes. 2o to clindamycin/ampicillin. Watery diarrhea, abdominal pain, anorexia, malaise, fever.

Irritable Bowel Syndrome Recurrent abdominal pain with 2 or more: pain improves with

defecation, changing stool frequency, changing stool appearance. Middle-aged women, chronic, may have diarrhea/constipation.

Inflammatory Bowel Disease Crohn’s disease: rectal sparing, transmural, “string sign” on Ba

swallow, Th1 mediated. Ulcerative colitis: continuous until rectal, bloody diarrhea, “lead

pipe” appearance on imagining, Th2 mediated.

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DIFFERENTIAL DIAGNOSIS – 2/3 Infections (watery diarrhea):

Vibrio cholera: cAMP, Gs

C. perfringens: gas gangrene, lecithinase α toxin Protozoa: Giardia (foul-smelling, campers/hikers, fatty diarrhea,

trophozoites/cysts in stool), Cryptosporidium (AIDS pts) Strongyloids stercoralis: larvae in soil penetrate through skin Enterotoxigenic E.coli: traveler’s diarrhea, ST & LT toxins Viruses: Rotavirus (dsRNA), norovirus (ssRNA)

Endocrine disorders: hyperthyroidism, diabetic gastroparesis, niacin deficiency

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DIFFERENTIAL DIAGNOSIS – 3/3 Malabsorption syndromes:

Whipple’s: Tropheryma whipplei (gram+), PAS+, foamy macrophages, [CVS, arthralgias, neuro.] symptoms, older men.

Celiac spruce (autoantibodies to gluten): distal duodemum, proximal jejunum, loss of villi.

Disaccharidase deficiency (lactase): normal villi, lactase located at tips of villi, can occur following injury (e.g., viral diarrhea).

Pancreatic insufficiency: cystic fibrosis, cancer, chronic pancreatitis, fat in stool.

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PATHOPHYSIOLOGY

Bacterial flora of colon disturbed C. difficile colonize toxins released mucosal inflammation and damage

Antibiotics: ampicillin/amoxicillin, clindamycin, cephalosporins (esp. 2nd & 3rd gen.), and fluoroquinolones

ToxA (enterotoxin) or ToxB (cytotoxin) bind cell surface receptor endocytosis of toxin-receptor complex low endosome pH leads to pore-formation glucosyltransferase (GTF) & protease translocation into cytosol

cysteine protease domain activated by inositol hexakisphosphate (InsP6) cofactor, cleaves toxin, releases GTF domain into cytosol RHO-family gets glycosylated RHO GTPase inactivated

RHO proteins: assist in actin polymerization, cytoskeletal architecture, and cell movement Inflammation & damage

FOUR DOMAINS OF TOXA / TOXB (C. DIFFICILE)1. Domain B (green): carboxy-

terminal 'binding' domain binds to a cell surface receptor

2. Domain D (yellow): the 'delivery‘ domain is involved in translocation of the toxin into the cytosol

3. Domain C (blue): cysteine protease 'cutting' domain

4. Domain A (red): biologically active glucosyltransferase domain

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FINDINGS TO SUPPORT DIAGNOSIS – 1/3 Leukocytosis (15,000 μL)

Acute kidney injury: Elevated WBC and Creatinine (1.5x pre-morbid level)

Electrolyte imbalances, dehydration, hypoalbuminemia, anasarca

Stool Examination & Stool Assay’s: 1. Culture (gold-standard)2. Glutamate dehydrogenase (GDH) enzyme immunoassay

(EIA)3. Real-time PCR gene toxin4. Cell cytotoxic assay5. EIA for ToxA and ToxB6. Latex agglutination to detect GDH

Guidelines suggest: # 2 (detection) & # 4 (confirmation)

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FINDINGS TO SUPPORT DIAGNOSIS – 2/3 Endoscopy: raised, yellowish white, 2- to 10-mm

plaques overlying an erythematous, edematous mucosa

Histologic: biopsy reveals an inflammatory exudate composed of mucinous debris, fibrin, necrotic epithelial cells and polymorphonuclear cells

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FINDINGS TO SUPPORT DIAGNOSIS – 3/3 Computed Tomography Scanning: Marked colonic

wall thickening. Ascites, irregularity of bowel wall, pericolonic stranding, megacolon.

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TREATMENT OPTIONS – 1/2

Pharmacological: Mild-Moderate: metronidazole / vancomycin PO (10-14 d) Severe-complicated: empirical vancomycin PO (10-14 d) Relapse from mild-moderate:

1st relapse: metronidazole (forms free radical metabolites in bacteria) 2nd relapse: vancomycin (binds D-ala D-ala of cell wall precursors)

Probiotics may be useful for prevention

Fecal Microbiota Transplanation: transfer healthy donor stool to C. difficile infected patient reconstituting normal colonic flora Very promising results!

Surgical: fulminant colitis & toxic megacolon require surgical intervention

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TREATMENT OPTIONS – 2/2 – IDSA & SHEA GUIDELINES

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REFERENCES

1. http://radiographics.rsna.org/content/20/2/399/F39.expansion.html

2. http://www.uptodate.com/contents/chronic-diarrhea-in-adults-beyond-the-basics

3. http://emedicine.medscape.com/article/186458-overview#aw2aab6b2b2

4. http://www.nature.com/nrmicro/journal/v9/n7/box/nrmicro2592_BX1.html

5. http://emedicine.medscape.com/article/186458-workup#a0756

6. http://emedicine.medscape.com/article/186458-workup#aw2aab6b5b3

7. http://eguideline.guidelinecentral.com/i/53988#

8. http://us.123rf.com/400wm/400/400/mscates/mscates1201/mscates120100011/11870590-a-doctor-with-a-thumbs-up-sign-isolated-on-white.jpg

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THANK YOU FOR LISTENING…

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APPENDIX