A Common presentation of an uncommon disease

By

Dr. Muhammad Arshad

Specialist Internist

Fellow College of Physicians and Surgeons, Pakistan

KKH Tabuk, KSA

Does a Common presentation of an uncommon disease means ?

a) A common disease presenting in atypical way.

b) A rare disease presenting in atypical way.

c) A common disease presenting typically.

d) A rare disease presenting typically.

Personal Profile 38 years old lady, married last 10

years ,house wife, with out any issue, admitted via E.R with presenting complaints of

Abdominal distention - 6 months B/L leg oedema - 6 months Loose motions - 4 months

History of presenting complaints

• Abdominal distention gradual onset,

preceded by pedal oedema, worse in evening

• No history of cough, sputum ,fever, chest pain, orthopnea, PND, and urinary symptoms

• After 2 months of above symptoms diarrhea

started, watery, large volume, 5-6 episodes in day and 5-6 episodes in night, no blood or mucus with stools, no history of vomiting,

History Cont--

Personal History : Illiterate ,non smokerSocioeconomic History: Residing with

husband, Bedouin, average

livingFood and Drug History: No history of any

Food or drug allergy

Past History Three admissions in last 2 years First admission Symptoms at presentation were Backache Headache Dizziness and Fatigue

InvestigationsHb 5.8 G/dl

MCV 67.2

Albumin T Protein

29 G/L 61G/l

TLC 6×103 Calcium Corrected

2.02mmol2.22

Plts 392 ×103 Iron 2

ESR 20 TIBC 80Urea 6.4 AST

ALT2849

Creat 92 AlkPhos

158

Uric Acid 3.2 T Bil 15

Discharge diagnosis Iron deficieny anemia On Ferrous sulfate Folic acid

2nd admission

Symptoms at admission were Generalized weakness and symptoms of anemia Headache Dizziness and Fatigue

Investigations Hb 7.95 G/dl

MCV 57.2

Albumin T Protein

15 G/L 43G/l

TLC 5.8×103 Calcium Corrected

1.71mmol2.13

Plts 305 ×103 Iron 2

ESR 30 TIBC 16 ( 45-81)

Urea 5.3 AST ALT

6056

Creat 82 AlkPhos

258(136-145)

Uric Acid 3.2 T Bil 15

Ultrasound AbdomenLiver size 14cm,generalized increasedechogenisity (Fatty change)Portal vein 1.4 cmMild splenomegalyMinimal Ascites

?? Chronic liver disease Correlate clinically

Investigations PT 18.3/18.27 Calcium

Corrected 1.81mmol2.17

aPTT 40.6/40.57 Iron 2

INR 1.7 TIBC 16 ( 45-81)

TSH .005 ALT AST

23.758.9

FT4 11.66 AlkPhos

358(136-145)

Magnesium

o.77 T Bil 13

Investigations Endocrinologist opinion : Sick

euthyroid

Hepatitis B and C Serology = Negative

Transfused 2 units of Red Cell Concentrate

Discharge Diagnosis Iron deficiency anemia Hypothyriodism Liver cirrhosis

Advised to follow OPD

Patient visited OPD with fresh Biochem

Albumin = 21 G/dl , Total Protein= 42 G/dl Calcium = 1.71 mmol/L, Corrected = 2.06 Serum Ferritin= 26.30 RFTs and blood glucose = Normal ALT =148 and AST = 197, Alk Phos = 463 (136-145) T. Bil= 10.8, D.Bil = 3.3 PT=16.3/16.27, aPTT = 45.3/45.5, INR = 1.37 Repeat Hepatitis B and C serology

=Negative

3rd admission Symptoms written on refferal were Amenorrhea B/L pedal pitting oedema Diarrhea with weight loss, fatigue Dyspepsia H/o anemia and blood transfusion

Investigations Hb 6.95 G/dl

MCV 57.2

Albumin T Protein

19.3 G/L 38.8 G/l

TLC 7.8×103 PT 18.3/18.27

Plts 175 ×103 aPTT 40.6/40.57

Na 141 INR 1.3

K 2.93 AST ALT

6194.4

Creat 82 AlkPhos

230(136-145)

Urea 3.2 T Bil 15

Investigations Thyroid profile repeated FT4 =11.35 and FT4= 11.89

Ultrasound Abdomen Generalized increased echogenisity (Fatty change) Portal vein 1.5 cm Splenomegaly 16 cm Moderate Ascites

?? Chronic liver disease Correlate clinically

Plan:

Referral to higher centre for evaluation of cause of

Chronic liver disease but family refused

Patient discharged with diagnosis

Liver cirrhosis , cause ? Sub clinical hypothyroidism Iron deficiency anemia

On

Iron, Spironolactone , Lactulose, Multivitamin and frusemide

Summary A 38 yrs old Saudi female, marriedissueless , frequent admissions with symptoms of anemia, wt loss,

generalized oedema, presently admitted with H/O abdominal distention , B/L leg oedema

, loose motions 4-6 months

What is Differential Diagnosis ?

1) Chronic Liver Disease 2) Malabsorption syndrome Cause ? 3) Chronic infection of GUT Tuberculosis Giardiasis -etc 4) Cardiac cause Constrictive pericarditis

On ExaminationA thin slim wasted lady, average hight,conscious, orienated, lying comfortably on bed. Weight: 30Kg BP: 123/70, Pulse : 92/min, Temp: 37c, Spo2: 98% room air JVP: Not raisedPedal oedema: B/L Pitting +++No lymphadenopathyPallor: +++No peripheral signs of CLD

Systemic Examination Abdomen: Protuberant, flanks Full, No Scar or Abnormal vessel Liver Size 12-13 cm Spleen enlarged 2 fingers below costal

margin Fluid thrill and shifting dullness: ++

CVS : Unremarkable CNS : Unremarkable Chest : Unremarkable

What is Differential Diagnosis ?

1) Malabsorption syndrome Cause ? 2) Chronic infection of GUT Tuberculosis Giardiasis , etc 3) Cardiac cause Constrictive pericarditis 4) Ch. Liver Disease

Investigations Hb 9.7 G/dl

MCV 87.3Albumin T Protein

16 G/L 46G/l

TLC 5.07×103 Calcium Corrected

2.05mmol2.51

Plts 135 ×103 PT 16.4/16.3

ESR 30 aPTT 37.4/37.4

Urea 5.3 AST ALT

8453

Creat 82 AlkPhos

542(136-145)

INR 1.5 , 1.6 T Bil 11.9

Investigations Stool Examination: No ova or cysts No fecal

leukocytes No occult blood

noted

Ultrasound Abdomen Liver size 14cm with homogenous echo texture (Fatty change) Portal vein 1.4 cm Splenomegaly 14 cm Moderate Ascites Normal size kidneys Doppler for hepatic veins= Normal

flow, No sign of Budd Chiari syndrome

Chest X-Ray ECG

Echocardiography

All Normal study

CT scan abdomen with contrastNormal size liver, minimally dilated portal vein

and splenomegaly. Normal flow of blood in

hepatic veins and inferior vena cava.

Dilated small bowel loops with generalized

increased mucosal fold thickness

Impression= protein losing enteropathy vs Inflammatory bowel disease

C.T Abdomen

Thickening of mucosal wall

Findings of malabsorption at barium examination. • (a) Image shows duodenitis with nodularity in a fold-free duodenum. • (b) Image shows flocculation, dilution, and dilatation . • (c) Image shows moulage, which is a featureless bald appearance of the jejunum caused by atrophy of folds and wall edema.• (d) Image shows reversal of the fold pattern, with more prominent folds in the ileum than in the jejunum.

• CT Bests Barium in Adult Celiac Disease Diagnosis• By Todd Neff |July 22, 2011• Improvements in computed tomography (CT)

resolution of the small bowel, colon, and mesenteric lymph nodes have pushed CT scans ahead of traditional barium examinations in the diagnosis of celiac disease, according to a new study in the journal RadioGraphics.

• The study, led by Francis Scholz, MD, a radiologist in the Lahey Clinic in Burlington, Mass., reviewed CT findings from more than 200 cases of celiac disease from 1996 to 2009. The CT scans highlighted abnormal structural changes known to result from the disease, and in more detail than possible with a traditional barium examination, Scholz and colleagues said.

Ascitic Fluid WBC 75/cmm RBC 500/cmm Lymphocytes 95% No AFB seen TP 5G/L Albumin 3.8G/L SAAG >1.2 Glucose 5.6 Cytology No malignant cells

seen

Upper GIT Endoscopy Esophagus = normal, no varices Stomach = normal, except pale

mucosa Duodenum=Flattening of mucosal

folds and inflammatory exaudate was

noted D2 biopsy was taken

Histopathology report Total villous atrophy ,with

increased intraepithelial lymphocytes, crepts hyperplasia and infiltration of lamina propria with plasma cells and lymphocytes.

Consistent with Celiac disease (Gluten sensitive enteropathy)

Normal D2 Histology

Histology

After Treatment

Marsh Classificationstage 0: preinfiltrative mucosastage 1: infiltration of the lamina propria with lymphocytes stage 2: Crypt hyperplasiastage 3: villus atrophy with infiltration of lamina propria with lymphocytes ,plasma cellsstage 4: total mucosal atrophy, characterized by complete loss of villi, enhanced apoptosis,and crypt hyperplasia

Causes of Villous Atropy Giardiasis Zollinger-Ellison Syndrome Crohn,disease Tropical sprue Small Intestinal Lymphoma Graft-Verses host disease Hypogammaglobulinemia Eosinophilic gastroenteritis Severe malnutrition Radiation or cytotoxic chemotherapy

Investigations Conti---

Serology for anti-endomysial : Positive

Diagnosis

Celiac disease

Treatment Advised strict dietary measures

regarding Gluten free diet Nutritional Supplements -Calcium -Iron -Folic acid Patient responded to treatment -Weight gained -Edema settled -Anemia improving

Celiac Disease• T-cell mediated autoimmune inflammatory disorder of small bowel

• Intolerance to gluten protein (alcohol Soluble Prolamin ) found in Wheat, Rye , Barley and Oats

• Prevalence variable world wide, in UK 1 in 200, • 1 in 300-1500 in rest of world , more common in Irish

• 10% prevelance in 1st degree relatives

• 30% relative risk in siblings

• 50% individuals are asymptomatic

as Silent cases and latent celiac disease

Pathogenesis

Still unknown

Clinical Features Can present at any age Two peaks In infancy, In adults 3rd -5th decades of life In infancy: At weaning, infants and children present with diarrhea, symptoms of malabsorption, failure to thrive and short stature.So affected child had both growth and pubertal delay

Clinical features• In adults peak onset 3rd - 5th decade,

• Females affected more than males

• Presentation highly variable, depending on

• severity and extent of small bowel involvement

• Female may land in Gynae floor with primary

amenorrhea and infertility

• Patient may land in surgical floor with fracture

Clinical featuresMostly adults present with diarrhea ,

steatorrhea , abdominal pain, tiredness,

weight loss, Anemia, bone pains, osteomalacia oral ulceration (Apthus), angular

stomatitis Dyspepsia, and bloating - ( IBS ? )Many patients present with iron

deficiency anemia alone.

Clinical presentation can be:

Gliadan Shock: Massive watery diarrhea just like

acute cholera within hours of eating cereal containing gluten by a patient who was on treatment with gluten free diet

Acute Celiac Crises

Manifested by Severe diarrhea,

dehydration, weight loss, acidosis,

hypocalcemia, and hypoproteinemia

Refractory Celiac Symptomatic severe small

intestinal villus atrophy that does not

respond to at least 6 months of a strict gluten-free diet and this villus atrophy is not caused by any

other disease or overt intestinal

lymphoma

Causes of Villous AtropyGiardiasisZollinger-Ellison SyndromeCrohn,s diseaseTropical sprueSmall Intestinal LymphomaGraft-Verses host diseaseHypogammaglobulinemiaEosinophilic gastroenteritisSevere malnutritionRadiation or cytotoxic chemotherapy

Extra intestinal Manifestations Anemia, any type  Hemorrhage ThrombocytosisOsteopenia, Pathologic fractures , Osteoarthropathy Muscular AtrophyTetany   Weakness Generalized Elevated liver enzymes, NASH,NAFLD Peripheral neuropathy , Ataxia Cerebellar and posterior column damage, SeizuresSecondary hyperparathyroidism,  Amenorrhea, infertility, impotence, hypothalamic-pituitary dysfunction Follicular hyperkeratosis and dermatitis, Petechiae and

ecchymoses Edema HypoproteinemiaDermatitis herpetiformis

Definite Association Dermatitis herpetiformis Type 1 diabetes mellitus 2-8 % Hypothyroidism/hyperthyroidism 5%, IgA deficiency 2 % Epilepsy with cerebral calcification Inflammatory bowel disease, and Microscopic colitis Primary Billary Cirrhosis 3% IgA mesangial nephropathy Rheumatoid arthritis Down syndrome Fibrosing alveolitis, Bird-fancier's lung Recurrent pericarditis Idiopathic pulmonary hemosiderosis Sjogren,s Syndrome 3 % Sarcoidosis

Possible Association

Congenital heart disease, Cavitary lung disease Systemic and cutaneous vasculitis Systemic lupus erythematosus, Polymyositis Myasthenia gravis, Iridocyclitis or choroiditis Cystic fibrosis, Macroamylasemia Addison's disease Autoimmune thrombocytopenic purpura Autoimmune hemolytic anemia Schizophrenia, Autoimmune liver diseases

Diagnosis History - Symptoms of Anemia and malabsorption Examination Investigation CBC with peripheral film may show

target cells, spherocytes, and Howell-Jolly bodies

Biochem, esp Serum Calcium, iron, folate, B12, phosphate, magnesium, Vit D levels

ALT, AST, Alk Phos DEXA scan for metabolic bone disease

Upper GIT endoscopy with D2 Biopsy Anti-endomysial and Anti tTG antibodies 85-95 % sensitive and 99% specific

However need to check IgG antibodies in IgA

deficient individual

Become negative with successful treatment

Treatment

Key Elements in the Management of Celiac Sprue

• C onsultation with a skilled dietitian • E ducation about the disease   • L ifelong adherence to a gluten-free

diet   • I dentification and treatment of nutritional deficiencies    • A ccess to an advocacy group   • C ontinuous long-term follow-up

Gluten free diet No intake of products made of Wheat Barley Rye OatsCan take foods as Rice , Maize , potato

meat, fish, chicken, vegetables, fruits

Immunosuppressive drugsindicated

Gliadin Shock Acute Celiac crises Refractory Celiac disease

Complications Increased risk of enteropathy

associated T-cell lymphoma, Small bowel

carcinoma, Squamous carcinoma of oesophagus,

and Metabolic bone disease Ulcerative jejunoiletis Collagenous collitis and Sprue

PrognosisExcellent Prognosis: If early diagnosis and treatmentMalnutrition and even death(complications) if diagnosed late and no treatmentEarly treatment: restore normal absorptive functionsAdvanced complications may not be completely reversed such as neuropathy or ataxiaIts not always a life long condition10-20 % of children become Tolerant to glutenOther develop latent celiac sprue

Message

Celiac disease should be included in differential diagnosis of unexplained

Iron

deficiency anemia and malabsorption

Swat valley of Pakistan THANKS ALL