Cases from the Clinic Maryland ACP Meeting January 30, 2016
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1 Cases from the Clinic Maryland ACP Meeting January 30, 2016 Bimal Ashar, MD, FACP D. William Schlott, MD Associate Professor of Medicine Johns Hopkins University School of Medicine 1
2 CASE 1: GK 46-year-old gentleman who presents to establish care Complained of a 5-year history (started at age 41) of intermittent abdominal pain and bloating: Diffuse around the epigastrium Associated with fevers, chills, and nausea at times Not typically related to eating Experiences diarrhea and constipation at times (not consistent) No distinct periodicity to the attacks 2
3 GK History PMH: Intermittent low back pain, Right inguinal hernia PSH: Lasik surgery, tonsillectomy MEDS: None SH: Never smoked, drinks 1-2 drinks per week, no history of drug use Employment: Environmental engineer works in an office. No known occupational exposures FH: Mother was a diabetic who died at 84 of stroke; Father died at 70 of CHF 3
4 GK Chart review Comprehensive metabolic panel normal Amylase and lipase normal Complete blood count normal CT scan and ultrasound of abdomen revealed gallstones with no evidence of ductal dilatation or gallbladder wall thickening 4
5 GK Continued Underwent cholecystectomy but pain recurred Subsequently had colonoscopy, upper endoscopy, and upper GI series that were all unremarkable Ultimately treated with anti-spasmodics for irritable bowel but did not seem to help What now?? 5
6 Differential Diagnosis Irritable bowel Inflammatory bowel disease Pancreatitis Renal colic Intermittent intestinal obstruction (intussusception, hernia) Peptic ulcer disease Abdominal migraine Mesenteric ischemia Behcet s disease Diverticulitis Acute intermittent porphyria Hereditary periodic fever syndrome (e.g., Familial Mediterranean fever) 6
7 GK During an attack HPI: Left-sided abdominal pain for about 24 hours. No nausea, vomiting, diarrhea, constipation, melena, or hematochezia Physical exam VS: T 37.4 C (99.4 F), P 100, BP 140/80 GA: No acute distress Abdomen: Soft, non-distended, left-sided to epigastric tenderness. No rebound/guarding 7
8 GK--Labs Initial Visit During Attack ESR (mm/hr) WBC (per mm 3) 5.9K 12.2K Urine red cells/white cells None None LFT s Normal Normal Amylase/lipase -- Normal Abdominal CT -- Unremarkable 8
9 Differential Diagnosis Irritable bowel Inflammatory bowel disease Pancreatitis Renal colic Intermittent intestinal obstruction (intussusception, hernia) Peptic ulcer disease Abdominal migraine Mesenteric ischemia Behcet s disease Diverticulitis Acute intermittent porphyria Hereditary periodic fever syndrome (e.g., Familial Mediterranean fever) 9 9
10 GK--Labs 24-hour urine for porphobilinogen and δ- aminolevulinic acid was normal Presumptive diagnosis: Familial Mediterranean Fever (FMF) 10
11 FMF Overview Autosomal recessive genetic disorder Primarily affects populations surrounding the Mediterranean basin Characterized by recurrent attacks of fever, peritonitis, pleuritis, arthritis, or erysipelas-like skin disease 11
12 FMF Historical Perspective 1 st case probably described by Theodore Janeway in 1908 Described as a distinct disease Benign Paroxysmal Peritonitis in 1945 FMF gene (MEFV) cloned in
13 MEFV Gene Maps to the short arm of chromosome 16 Predominantly expressed in neutrophils More than 50 mutations have been identified Most reported cases result from 5 mutations Encodes a protein called pyrin (marenostrin) that is thought to repress a pro-inflammatory molecule and/or up-regulate an antiinflammatory protein 13
14 Structure of the Gene for Familial Mediterranean Fever (MEFV ) Drenth, J. P. H. et al. N Engl J Med 2001;345:
15 Epidemiology Primarily affects Armenian, Arab, North African, Turkish, and Jewish populations Prevalence may be as high as 1:200 in certain populations Cases now seen throughout the world 15
16 Clinical Presentation 90% of patients present before age 20 Attacks usually last 1-3 days and recur within weeks to months Severity of attacks can vary Labs: Increased acute phase reactants 16
17 Diagnosis Usually based upon clinical presentation Tel Hashomer criteria: (Livneh, et al. Arthritis Rheum 1997;40: ) Major criteria: recurrent febrile episodes with serositis, amyloidosis type AA without predisoposing disease, favorable response to colchicine Minor criteria: Recurrent febrile episodes, erysipelas-like erythema, FMF in a 1 st degree relative Definitive Dx: 2 major or 1 major and 2 minor Role of genetic testing? 17
18 Treatment Colchicine is the mainstay of therapy based on observations in the 1970 s Observational studies show that it can decrease the number and intensity of attacks and prevent the development of amyloidosis Mechanism is unclear but probably acts in a number of ways to inhibit the inflammatory response and prevent assembly of amyloid fibrils Dose in adults is 1-2 mg/day 18
19 Back to GK Started on a trial of colchicine at 0.6 mg BID Genetic test obtained revealing that he is homozygous for the V726A mutation Has not had an attack in 15 years 19
20 Learning Points 1. FMF can be seen in patients of virtually all ethnic backgrounds 2. Attacks do not need to be severe 3. Genetic testing can play a role in diagnosis 4. Colchicine is very effective for prevention of attacks and development of amyloidosis 20
21 Case 2: DC 66-year-old gentleman with a history of GERD who presents for consultation regarding cough and fatigue Reports a history of recurrent bronchitis (4 long bouts over 2 years) Most recently was diagnosed with bronchitis in 6 months prior to presentation but symptoms did not improve with antibiotics Cough described as non-productive fits of coughing throughout the day. He is typically able to sleep at night. SH: 15 pack-year history of cigarettes quit 30 years ago MEDS: Ranitidine plus numerous supplements 21
22 DC Chronic cough Common causes Post-nasal drip Asthma GERD Post-infectious cough syndrome Medications: ACE inhibitors Less common causes Bronchiectasis Chronic bronchitis Nonasthmatic eosinophilic bronchitis Bronchogenic carcinoma Interstitial lung disease Occult heart failure Occult aspiration 22
23 DC-Review of records ESR WBC and Hgb Plt AST ALT Alkaline phosphatase Blood work 90 mm/hr Normal 357K/cu mm Normal 44 U/L 197 U/L Other tests Chest x-ray and CT of chest unremarkable FEV1/FVC 112% predicted with normal flow volume loops RUQ ultrasound no abnormalities 23
24 DC More history Patient reported that in addition to antibiotics, he had been put on varying doses of prednisone over the previous 6 months, during which time his symptoms do improve Denied fevers, chills, nausea, vomiting, hearing or vision changes, or weight loss Upon questioning, developed frontal headaches that radiate to the top and back of his skull about 2 months ago Eyeballs feel heavy MRI of head done 3 weeks prior to presentation showed only mild periventricular white matter changes 24
25 DC Physical exam VS: Temperature 97.2, pulse 90, respiratory rate 20, blood pressure 150/84, weight of 157 lbs GA: Pleasant gentleman in no acute distress HEENT: No papilledema. No sinus tenderness. No temporal artery prominence or tenderness Neck: No JVD, lymphadenopathy, or thyromegaly Chest: Clear, no wheezing or egophony. Good air movement Heart: No murmurs Neuro: No focal deficits 25
26 DC Case summary 66-year-old man with 6 month history of cough and fatigue and 2 month history of frontal headaches which improve with prednisone Labs reveal elevation of inflammatory markers and alkaline phosphatase A diagnostic procedure was done 26
27 DC Temporal artery biopsy From: 27
28 Temporal arteritis Classic presentations Finding Frequency, % ESR > 40 mm/hr 94 Headache 77 Abnormal temporal artery 53 Jaw claudication 51 Constitutional symptoms 48 Polymyalgia rheumatica 34 Visual symptoms 29 Fever 26 From Hellmann, DB. JAMA 2002; Original data from Machado EBV, et al. Arthritis Rheum 1988;31:747 28
29 Temporal arteritis Laboratory abnormalities Lab Frequency, % Anemia (Hgb < 12 g/dl) 55 Thrombocytosis (>400K/cu mm) 49 Leukocytosis (>11K/cu mm) 28 Hypoalbuminemia (<3 g/dl) 28 Elevated alkaline phosphatase (>2x normal) 25 From: Gonzalez-Gay MA, et al. Medicine 2005; 84:
30 Temporal arteritis: Respiratory symptoms Include cough, sore throat, hoarseness, choking sensation, sore tongue, chest pain Estimated 9% of patients with TA have respiratory symptoms 4% have respiratory symptoms as their chief complaint Larson TS, et al. Ann Int Med 1984;101:
31 Back to DC Treated with 60 mg of prednisone Followed up with local rheumatologist and did well 31
32 Learning points 1. Cough and respiratory symptoms can be manifestations of temporal arteritis and can rarely be the presenting symptom 2. Alkaline phosphatase is frequently elevated in cases of TA 32
33 THANK YOU 33
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