6/24/2009. Representative photo

Transcription

1 Advances in Internal Medicine UCSF CME June 24 th, 2009 Discussant: Dr. Harry Hollander A 62 year old woman presents with dyspnea on exertion and abdominal swelling. HPI Previously unlimited exercise tolerance, progressive dyspnea over 1 year For the past month, able to walk <1 block before getting SOB and stopping No CP, orthopnea, PND, palpitations Chronic non-productive cough No fevers/chills, no night sweats 1

2 HPI ~2-3 month ago: diffuse, migrating abdominal pain Pain persisted for 1 month, then resolved ~1 month ago: abdominal girth increased rapidly Swelling also in both legs Normal appetite, normal BM, no early satiety No nausea/vomiting ROS Denies weight loss, but family members note that she seems much thinner in her face and arms. Fingers turn blue, especially in the cold; worsening over the last year without associated pain. L ankle pain w/ movement Additional History PMHx: HTN well controlled, L eye blindness after an infection 1 year ago Medications: None Originally from China, immigrated to US 5 years ago. Lives alone. No cigarettes, alcohol, or drugs Father: HTN and renal failure Mother: cancer and Parkinson s 2

3 Physical Exam / %RA Gen: Cachectic, NAD HEENT: anicteric, L pupil clouded, OP clear, no LAD CV: JVP <7cm, regular, normal S1/S2, no murmurs or rubs Lungs: R: CTA; breath sounds & dullness to percussion at left base Abdomen: distended, soft, normal bowel sounds, dull to percussion over flanks, no HSM, liver edge not palpable, no caput medusae Ext: 2+ bilateral pitting edema to knees, dependent edema over buttocks; 2+ distal pulses Physical Exam MSK: Ankle: bilateral edema, no synovitis, pain w/ L ankle movement All other joints normal L hand: acral cyanosis all digits, no ulcerations or necrosis, normal nail beds w/o dilated capillary loops Skin: Telangiectasias on both cheeks; none on trunk, no spider angiomata acral discoloration as noted; slight blanching erythema anterior ankles bilaterally no other rashes or lesions, no petechiae, pupura, or ulcerations; no skin thickening Neuro: normal exam Representative photo Skin exam 3

4 Data Diff: PMN 70% L 26% M 3% E 1% MCV: INR 1.3, Albumin 2.7, TP 8.2, LDH 244 UA: trace protein EKG: NSR 4

5 Abdominal U/S Liver diffusely heterogeneous and shrunken, with evidence of contour nodularity No focal liver masses Patent vessels, normal flow by doppler Extensive gallbladder wall thickening; without stones, pericholecystic fluid, or ductal dilatation Spleen 10.6cm (slightly large for pt size) Mild to moderate ascites Similar findings on CT Other Studies TTE: normal except for non-hemodynamically significant myxomatous valvular changes. Blood cultures negative. 5

6 RBC 560 Paracentesis fluid WBC 107 PMN 0%, Lymph 40%, Mono 60% Total protein undetectable Albumin undetectable Gram stain, AFB smear, fungal stains: negative Cytology: negative RBC 3440 Thoracentesis fluid WBC 269 PMN 2%, Lymph 52%, Mono 46% Glucose 90 Total protein 2.2 (serum 8.2) LDH 80 (serum 244) Gram stain, AFB smear, fungal stains: negative Cytology: negative Additional lab workup Hep A: IgM (-), total Ab (+) Hep B sag (-), BcAb (+), core IgM (-) Hep Bs Ab (+) HCV Ab (-) TSH 1.86, FT4 normal Iron 29, Ferritin 38, Transferrin 183, % Sat 13 Ceruloplasmin 29 (WNL) AFP 2.6, CEA 1.7, CA (normal <35) 6

7 Hospital Course Edema, ascites, and exercise tolerance improved with furosemide and spironolactone. Additional workup was sent. Additional lab workup Additional lab workup Hep B and C viral load: negative UPEP negative SPEP: polyclonal IgG Mycobacterial culture: negative Fungal culture: negative ESR 93 ANA +1:640 dsdna +1:320 RF 48 Cryoglobulins: negative C3 and C4: normal SSA and SSB: negative Scl-70: negative Anti LKM: negative Anti smooth muscle: 21 (weakly positive) Anti Mitochondrial Ab: negative ANCA: negative Anti RNP: 87 (strongly positive) Serum IgG: 4500 mg/dl (ULN=1760) 7

8 A diagnostic procedure was performed Which of the following best explains her current presentation? 1. SLE 2. Tuberculosis 3. Metastatic cancer 4. Autoimmune hepatitis 5. Lymphoma 6. Clonorchis sinensis infection 8% 0% 4% 63% 2% 24%

9 Representative photo Liver biopsy : A23 Diagnosis: Autoimmune hepatitis Cirrhosis, but also areas of inflammation with interface activity and increased numbers of plasma cells Autoimmune Hepatitis (AIH) Relatively rare Point prevalence of 16.9/100,000 people 3:1 women to men predominance Wide age distribution Older patients are more likely to present with cirrhosis Pathophysiology is not well understood Overlap common with PBC, PSC, HCV, as well as multiple other autoimmune conditions Autoimmune Hepatitis: Clinical features Predominant transaminase elevation Cholestasis, if present, suggests overlap syndrome Elevated levels of IgG (usually >1.5 x ULN) Circulating Ab: ANA, Anti Smooth Muscle, or other Liver histology: inflammation interface hepatitis, lymphoplasmocytic necrosis, fibrosis plasma cell infiltrate 9

10 Slide 34 A23 change this slide to de-emphasize (even further) a "second" diagnosis - HH will likely get that concept but maybe not state dx #2 exactly like this; simpler to delete "with features of..." That makes it easier for him to be "right"...you could say how they are characterizing her overlap syndrome w/ the passage of time in the follow up slides...people will want to know that. Administrator, 6/5/2009

11 Autoimmune Hepatitis (AIH) Often divided into two subtypes. Type 1 or Classic Type 2 Type 1 AIH (most common) Positive ANA or SMA (anti-actin actin ab) Occurs at wide range of ages Frequently associated with other autoimmune diseases Other antibodies seen: Anti-mitochondrial (also seen in PBC) Anti-dsDNA (assoc with HLA DR4) p-anca (also assoc with PSC, UC) Anti-soluble liver antigen (anti-sla/lp) Type 2 AIH Positive anti-lkm antibody ANA and SMA usually negative Other antibodies: Anti-liver cytosol -1 (ALC1) Usually younger patients AIH Treatment Corticosteroids (usually with azathioprine) Treatment: symptoms or labs/histology Treatment in advanced disease is more controversial, though may be some benefit 75% patients achieve remission in 18 months but relapse is common Many patients require long term treatment 10

12 Follow-up This patient was presented at advanced age and late in the disease course. Some features of SLE and scleroderma were present liver abnormalities are seen in these diseases. Ongoing evaluation is underway to determine if she has an overlap syndrome (i.e. SLE or scleroderma as well as AIH) Follow-up Received standard therapy for cirrhosis and ascites with symptomatic improvement. Debate re: if treatment (steroids) would be beneficial with advanced cirrhosis She has not yet been treated with steroids, though with active inflammation on liver biopsy, she may benefit. Acknowledgements Charles Everett, MD and Alejandra Casillas, MD Mike Burgess, MD PhD and John Newman, MD PhD Brad Sharpe, MD Gurpreet Dhaliwal, MD And a special thank you to our discussant! Harry Hollander, M.D. 11