CASE PRESENTATIONDR ALOK DHUNGEL

PGR (WMW)

PATIENT PROFILE

• Name: Zubaida Rafique

• Age: 48 years

• Sex: Female

• Marital status: married, house wife

• Address: Samnabad, Lahore

• History obtained from patient daughter

• Admitted from emergency department

CHIEF COMPLAINTS

• Yellowish discoloration of skin and sclera for last four months

• Abdominal distension for last 1 months

• Constipation for last 4 days

• Per rectal bleeding for last 3 days

• Altered sensorium for last 1 day

HISTORY OF PRESENTING ILLNESS

• My patient was usual state of health 4 month back whenshe noticed yellowish discoloration of sclera which wasgradual in onset, first appeared in sclera and thenprogessed to face and then to whole body.

• Patient took medication from the local hospital after whichher yellow discoloration of body improved over next onemonth but didn’t completely disappeared.Patient also tookhakeem medications for 2 weeks but wasn’t improved andshe quited hakeem medication

HOPI• Jaundice was associated with anorexia, nausea,

malaise, lethargy and generalized body weakness.Patient also complains of dark color urine and palestool .

• There is no history of fever, weight loss,lumps andbumps in the body chronic abdominal pain,arthalgia ,rash, pigmentation, bluish discolation ofhands ,recurrent abortions, acne, photosensitivity,amenorrhea,early morning dark color urine or DVT,drug/alcohol intake, or pruritis preceding orfollowing jaundice,blood transfusion or travelabroad.

CONTD

• She also complained of abdominal distension for lastone month which was of gradual onset and progressivein nature. Initially there was fullness of flank whichgradually progressed to whole abdomen and then tothe lower limbs. It was not associated with abdominalpain, steatorhhea ,diarrhoea alternating withconstipation or fever.

• There is no history of orthopnea, PND, breathlessnesson exertion, arthralgias, rash or easybruisibility,frothing of urine,pluirisy.

•

• There is no history of dyspepsia.

CONTD

• She then developed constipation 4 days prior to presentation but there is no history of hemetemesisand malena.

• There is history of painless bleeding per rectum which was fresh, 50-60 ml in amount, 3-4 episodes per day for last three day.

• She developed altered state of consciousness which was gradual. Patient initially became confuse, drowsy and was not easily arousable.

SYSTEMIC INQUIRY

• No history of chronic headache,migraine, fits, visual disturbances, blackouts, abnormal behavior, psychosis, numbness or tingling sensations.

• No history of exertional dyspnoea, chest pain, body swelling, orthopnea, PND, peripheral vascular disease.

• No history of cough ,dyspnoea, orthodexia, pleurisy, wheezing or nasal discharge

• There is no history of dysuria, urgency, hesitancy and no history of polyuria or hematuria or renal colic or genitourinary ulcers

PAST HISTORY

• She is a known hypertensive for last 5 years and was non compliant to medicaton.

• She had prior history of IHD(ACS) 2 yrs back and left medication by herself after taking it for just 6 months.

• Diabetic for last 1 year and was taking sulphonylurea (Diamicron).

• s/p cholecystectomy 1 yrs back• There is no history of Tuberculosis

MENSTRUATION HISTORY

• Patient had regular menstrual cycle…

• She had menopause 2 yrs back

TREATMENT HISTORY

• She was under treatment for hypertension ,ischemic heart disease and diabetes but she was not taking her medications regularly

• She was taking treatment for jaundice for last 3-4 mth (vitamins ,hepamerz and risek)

FAMILY HISTORY

• No history of similar illness in her family

• Her father had ischemic heart disease ..he died of stroke at the age of sixty.

PERSONAL HISTORY

• Widow with three children (one son and two daughter)

• House wife

Drug history

• No known allergy to any drugs

Summary of hx

• 48 years female • Jaundice for last 4 mth• Abdominal distension for last 1 mth• Constipation for 4-5 days • Lower GI bleeding 3-4 days• Asoc for one day• History of lethargy,fatigue,malaise ,nausea, anorexia

and generalized body weakness• Weight loss• No history of orthopnea,PND,frothing of

urine,hematuria or any chronic chest illness

• history of Diabetes ,HTN ,ACS

Differential diagnosis after History

• Acute on chronic Decompensated Liver disease with portal hypertension

• Primary biliary cirrhosis

• Venoocclusive disease(budd-chiari syndrome)

• abdominal malignancy(CA head of pancreas ,lymphoma,HCC)

• Non alcohalic fatty liver disease progressing to cirrhosis

• Hemochromatosis

• Primary sclerosing cholangitis

Clinical examinations

General physical examination

• A middle aged lady lying on bed having branula on left arm ,nasogastric tube and foleysin situ and not oriented to TPP with following vitals:

• Pulse-68/minute regular• BP-100/60• T-Afebrile• RR-20/min

• Pallor+• Icterus+++• Pedal Edema+• Lymhadenopathy -• Cyanosis-• Bruises –• palmer erythema -• Spider naevi -• Duputyen’s contracture-• Parotid enlargement• Loss of body hair –• JVP not raised• Rash –• Xanthalesma and xanthomas-• Pigmentations-• Shiny nails-• Scratch marks -

Systemic examination

• Abdominal Examination-• Inspection- abdomen was distended, moving with

repiration, peristalsis is not visible, umbilicus central and horizontally slit, no scar, stria or prominent veins. Hernial orifices intact.

• Palpation- No rigidity or tenderness. Spleen is palpable 1 finger below the left costal margin. Liver not palpable

• Percussion- Shifting dullness present but fluidthrill abscent

• Ausultation- Bowel sounds 3 per minute of normal intensity,no audible bruits or rubs

Systemic examination

• CHEST- Abdomino thoracic respiration, equal expansion, trachea central. Normo vesicular breath sounds bilaterally with no added sounds heard

• CVS: Apex beat in fifth intercostal space in mid clavicularline

• 1st and 2nd heart sound heard with normal intensity and character.

• No added sounds or murmur heard

• CNS EXAMINATION:GCS E3V3M4 10/15……..No motor n sensory abnormality

Per rectal Examination, proctoscopy

• 2° Haemorrhoids were present at 3,9,11 O clock position

HISTORY IN SHORT

ON HISTORY ON EXAMINATIONS

• 48 years female • Jaundice for last 4 mth• Abdominal distension for last 1 mth• Constipation for 4-5 days • Lower GI bleeding 3-4 days• Asoc for one day• Nasal bleeding for last 2-3 days• History of lethargy malaise fatigue

and generalized body weakness ,nausea, anorexia

• Weight loss• Cholecystectomy

• history of Diabetes ,HTN ,IHD

• Pallor

• Icterus

• Edema

• Ascites

• Hemorrhoids

• Splenomegaly

Differentials after HX and PE

• Acute on chronic Decompensated Liver disease with portal hypertension

• Primary biliary cirrhosis

• Venoocclusive disease(budd-chiari syndrome)

• Hemochromatosis

• NAFLD progressing to cirrhosis

• Primary sclerosing cholangitis

Investigations

Cbc lfts

• WBC-5.5-- 5.7

• HB- 6.9--12

• Hct- 18--36.5

• MCV- 74-- 82

• MCH- 27--27

• MCHC-37--33

• Plt- 114—101

• ESR-120(outside)

• Bil- 3.6—15.2

• Conjugated 9.3

• Uncon- 5.9

• ALT- 111-155

• AST-92-122

• ALP-487-280

• Prot- 6.4

• Alb- 3.3

Rfts PT /APTT

• Urea-20--26

• Cret-1.0– 0.5

• Na-136--136

• K-4—3.5

• PT /CONTROL-12/13

• APTT/CONTROL-32/33

ECG Chest xray

• NORMAL • NORMAL

Urine RME Hepatitis profile

• COLOR- pale yellow

• Sp Gravity- 1.025

• Ph- 6.0

• Protein- +

• Blood +++

• Pus Cell 15-20

• Red Cell- 25-30

• Epithelial Cell 2-3

• Hepatitis B- Neg

• Hep C- Neg

• Hep A- Neg

• Hep E- Neg

Usg abdomen and pelvis AFP

• Liver 14 cm

• Texure slightly Coarse

• Portal Vein 17 cm

• CBD Normal

• GB- Absent

• Spleen 15 Cm

• Splenic Varices seen

• Ascites present (moderate )

• 13 ng/ml (Normal upto 15)

Antibody tests send Fundoscopy

• ANA-

• ASMA-

• AMA-

• GAMMA GT- IU/ml

• No papilloedema

Final diagnosis

• Acute on chronic Decompensated Liver disease with portal hypertension with portosystemicencephalopathy grade III ( child pugh-C)

??cause

Common cause of CLD

• Chronic viral infections(B and C)• Chronic alcoh0lism• Non alcoh0lic fatty liver disease• Immunological(autoimmune liver disease and

primary sclerosing cholangitis)• Biliary(PBC and cystic fibrosis)• Genetic(wilson,hemochromatosis,alpha

antitrypsin deficiency)• Budd chiari syndrome• cryptogenic

Further work up

• Ascites fluid analysis• CT abdomen with contrast/biphasic CT scan• Usg doppler• MRI • Iron studies(serum iron ,TIBC and ferritin)• Serum ceruloplasmin level,s copper level and urinary copper• Alpha 1 antitrypsin level • Immunoglobulin levels• Anti thyroid antibodies level• ENA profile• Dexa scan • Calcium phosphate ,vit d levels• Fat soluble vitamins level• Opthalmologic examinations• Lipid profile

Primary biliary cirrhosis

• autoimmune disease

• antimitochondrial antibody (a highly disease-specific autoantibody found in 90%-95%)

• Fewer than 5% of patients with PBC are AMA-negative.

• Present in 4th to 6th decades

• Involvement of the small intrahepatic bile ducts

• Female male ratio=9:1

pathophysiology

• The exact mechanism of the liver damage is unknown, although evidence indicates that it can be of autoimmune origin.

• The data supporting this hypothesis are as follows:

• (1) abnormalities of the humoral and cellular immune systems (ie, elevated serum levels of immunoglobulins, mainly immunoglobulin M [IgM]),

• (2) multiple circulating autoantibodies,

• (3) granulomas in the liver and regional lymph nodes,

Contd..

• (4) impaired regulation of both B and T lymphocytes, and

• (5) the association of this disease with a variety of autoimmune-mediated diseases (eg, autoimmune thyroiditis; keratoconjunctivitis sicca; scleroderma; calcinosis cutis, Raynaud phenomenon, esophageal motility disorder, sclerodactyly, and telangiectasia [CREST] syndrome).

Clinical presentations

• Of patients with primary biliary cirrhosis, 25% are incidentally diagnosed during a routine blood evaluation.

• Fatigue (65%) Fatigue is the first reported symptom. It can cause disability in some patients and has been associated with depression and obsessive-compulsive behavior. The etiology is unknown; however, a sleep abnormality, particularly excessive daytime somnolence, has been identified in a significant proportion of patients and has been associated with the degree of fatigue.

• Pruritus (55%)According to estimates, 10% of patients experience severe pruritus.

• The cause of this symptom is not known.• Pruritus appears unrelated to the deposition of bile acids

in the skin.• Increased opioidergic tone (ie, increased production of

endogenous opioid peptides, up-regulation of endogenous opioid receptors) appears to be the major mechanism. The height of the bilirubin level is proportionally related to the production of these peptides.

• Right upper quadrant discomfort occurs in 8-17% of patients.

Physical findings

• Physical examination findings depend on the stage of the disease. In the early stages, examination findings are normal. As the disease advances, excoriations of the skin, xanthelasmata, or findings of cirrhosis may be present.

• Hepatomegaly (25%)• Hyperpigmentation (25%)• Splenomegaly (15%)• Jaundice (10%)• Xanthelasmata (10%) - In late stages of the disease• Sicca syndrome (50-75%) - Xerophthalmia (ie, dry eyes), xerostomia

(ie, dry mouth)• Kayser-Fleischer rings (extremely rare)• Stigmata of advanced liver disease (ie, cirrhosis), such as spider

nevi, palmar erythema, ascites, temporal and proximal muscle wasting, and peripheral edema

Criteria for diagnosis

1. The diagnosis of PBC can be established when

two of the following three criteria are met:

• ● Biochemical evidence of cholestasis based mainly on alkaline phosphatase elevation.

• ● Presence of AMA.

• ● Histologic evidence of nonsuppurativedestructive cholangitis and destruction of interlobular bile ducts

ddx

• Autoimmune Hepatitis

• Biliary Obstruction

• Graft Versus Host Disease

• Primary Sclerosing Cholangitis

• Sarcoidosis

Antimitochondrial antibodies

• The hallmark of this disease is the presence of antimitochondrial antibodies (AMAs) in the sera.AMAs can be found in 90-95% of patients with primary biliary cirrhosis, and they have a specificity of 98% for this disease.

• These antibodies target different components, mainly enzymes, in the mitochondria.

• The presence of anti-M2, anti-M4, anti-M8, and anti-M9 has been associated with the severity of primary biliary cirrhosis.

Lab investigations

• Lfts-cholestatic picture .increase gamma –GT,alkalinephosphatase ,AST and ALT

• Lipid profile –high cholesterol ,TG and HDL

• Auto antibody profile- A)AMA type -2 ,most specific and sensitive present in 90-95 %

• B)ANA-present in 15 -20 percent of the cases

• C)ASMA-present in 50%

• CBC- thrombocytopenia(indicates portal HTN)

Labs

• ESR- raised

• Calcium and vit-d levels-low

• PT/APTT – high in advanced disease

• Serum albumin-low

• Immunoglobulins-high esp IgM

• Serum bile acid level and ceruloplasmin level -high

imaging

• Abdominal ultrasonography, computed tomography (CT) scanning, or magnetic resonance imaging (MRI) are important to exclude biliary obstruction.

• Once patients are cirrhotic, findings compatible with portal hypertension (eg, nodular appearance of the liver, splenomegaly, intra-abdominal varices, ascites) can be observed.

• At this stage, follow-up imaging every 6 months with abdominal ultrasonography is suggested for early detection of hepatic malignancy.

treatment

• The goals of treatment are to slow the progression rate of the disease and to alleviate the symptoms (eg, pruritus, osteoporosis, sicca syndrome). Liver transplantation appears to be the only life-saving procedure.

• A.Ursodeoxycholic acid (UDCA) (13-15 mg per kg per day) is the major medication used to slow the progression of the disease. Patients with early disease have clinical, biochemical, and histologic improvement. Reports suggest that UDCA delays the need for transplantation or delays death. The efficacy of this medication in late stages (ie, cirrhosis) is questionable..

Treatment continued

• B.Immunosuppressive agents inhibit immune reactions that mediate the progression of the disease.

• Methotrexate: Results of various trials suggest improvement in biochemical and histologic findings after treatment.

• Corticosteroids may alleviate symptoms and improve biochemical and histologic findings. Corticosteroid-induced osteoporosis is of great concern. The dangers of using bisphosphonates requires further study.[11]

• Cyclosporine has some therapeutic potential.• Colchicine has been used to limited effect.

Treatment continued

• C.Antipruritic treatment• Antihistamines are first-line agents to relieve

pruritus in early stages and are the first line of medication for patients with mild-to-moderate pruritus. Use caution in patients with cirrhosis and signs of encephalopathy because antihistamines can further depress brain function.

• Cholestyramine (8-16 gm per day)and colestipolare effective in sequestering bile salts in the enteric lumen. A 1- to 4-day delay is expected before the itching remits.

• Rifampin (150-300mg bd)can also be used, but the precise mechanism of action is unclear . Rifampin is used in patients whose conditions are not responding to cholestyramine.

• Some evidence suggests that dronabinol(Marinol) can be used to good effect.

• Ondansetron- 8mg tds• Sertraline-25 mg -50mg hs• Plasmapheresis has also been implemented for

patients with severe pruritus intractable to medical treatment. Results have been good.

Surgical tx

• Liver transplantation

Follow up

• ● Liver tests every 3-6 months

• ● Thyroid status (TSH) annually

• ● Bone mineral densitometry every 2-4 years

• ● Vitamins A, D, K annually if bilirubin greater than 2.0

• ● Upper endoscopy every 1-3 years if cirrhotic

• ● Ultrasound and alpha fetoprotein in patients with known or suspected cirrhosis†

Associated autoimmune diseases

• Sicca syndromes 80%

• Systemic sclerosis 20%

• Coeliac disease

• Thyroid disease 20%

• Addison disease less than 5%

• Raynaud syndrome less than 5%

• SLE

• Mysthenia gravis

• vitiligo