Legionella pneumonia

Vignette says a 65 year old male with a history of chronic obstructive pulmonary disease presents to the pulmonology clinic with chief complaints of fever, cough and shortness of breath over the past few days; He also reports of fatigue, malaise, myalgias, headache and diarrhea over the past few days; He had recently completed his cruise ship travel prior to the appearance of above mentioned complaints; Vital signs show blood pressure of 110/70 mm of Hg, pulse rate of 58 bpm, respiratory rate of 18 breaths/min, oxygen saturation of 92% in RA and temperature of 101.2 F; CBC shows leukocytosis, RFT shows hyponatremia and LFT shows elevated AST & ALT; Urinary legionella antigen test is positive; Chest x-ray shows diffuse infiltrates; Diagnosis?

Diagnosis is Legionella pneumonia.

Presents with fever, cough, shortness of breath, myalgias, headache, and diarrhea; Classically acquired via aerosols.

Risk factors include older age, smoking, chronic lung disease and immunocompromised states.

Etiologies:-
1. Recent travel (e.g. hotels, cruise ships).
2. Exposure to contaminated water sources (air conditioning, hot tubs and fountains).

Diagnosis:-
1. Urine antigen test for the detection of Legionella antigen.
2. Sputum culture with BCYE agar shows Legionella growth.
3. CBC shows leukocytosis, RFT shows hyponatremia and LFT shows elevated AST & ALT.
4. Chest x-ray shows unilateral or bilateral patchy or diffuse infiltrates.

Management:-
1. Outpatient management is azithromycin or respiratory fluoroquinolone (i.e. levofloxacin).
2. Inpatient management is ceftriaxone and azithromycin.

Pseudomembranous colitis

Vignette says a 55 year old female presents to the emergency department with chief complaints of abdominal cramping, watery diarrhea, and a low-grade fever for the past 5 days; She was recently diagnosed with cystitis and was treated with ciprofloxacin; She denies any recent travel or known exposures to contaminated food or water; Abdominal examination is soft, mild tenderness on palpation and hyperactive bowel sounds on auscultation; Vital signs show blood pressure of 120/80 mm of Hg, pulse rate of 108 bpm, respiratory rate of 18 breaths/min, oxygen saturation of 92% in RA and temperature of 100.2 F; CBC shows WBC count of 12,000 cells/mm3; PCR test for Clostridium difficile toxin A and B are positive; Diagnosis?

Diagnosis is Pseudomembranous colitis.

Pseudomembranous colitis is caused by Clostridium difficile; often secondary to antibiotic use, especially clindamycin, ampicillin/amoxicillin, cephalosporin, fluoroquinolones; These antibiotics alter the normal intestinal flora favoring the growth of the clostridium difficile.

Clostridium difficile produces toxins A and B that damages the enterocytes; Toxin A (enterotoxin) damages the brush border whereas Toxin B (cytotoxin) damages the cytoskeleton.

Presents with fever, abdominal cramping, watery diarrhea, leukocytosis and toxic megacolon.

Diagnosis:- 

1. PCR or antigen detection of one or both toxins in stool; Clostridium difficile produces toxins A and B that damages the enterocytes.

Treatment:-

1. Stop the offending drugs.

2. Supportive measures like intravenous fluids and probiotics.

3. Antibiotics (e.g. oral vancomycin or fidaxomicin).

4. Fecal microbiota transplant in refractory cases. 

5. Monitor for complications such as toxic megacolon, perforation.

Figure:- Antibiotic Associated Diarrhea

Liddle syndrome

Vignettes says a 16 year old male presents to the cardiology clinic with persistent high blood pressure noted during a school health check-up; He has no significant past medical history and no family history of hypertension; He reports occasional muscle cramps and weakness; Vital signs show blood pressure of 160/100 mm of Hg, pulse rate of 78 bpm, respiratory rate of 18 breaths/min, oxygen saturation of 92% in RA and temperature of 97.9 F; Laboratory studies show serum sodium of 135mEq/L, serum potassium of 2.8 mEq/L, low plasma aldosterone, low plasma renin activity; Genetic testing reveals a mutation in the β-subunit of the epithelial sodium channel (ENaC); USG (A+P) is normal; Diagnosis?

Diagnosis is Liddle syndrome. 

Liddle syndrome is an autosomal dominant disorder due to mutation of epithelial Na+ channels (i.e. ENaC); causes increased absorption of sodium in collecting tubules (due to increased activity of ENaC).

Pathogenesis:- Normally, ENaC are degraded by ubiquitin proteasome pathway; Nedd4-2 (i.e. ubiquitin-protein ligase) binds with ENaC and facilitates its degradation. ENaC is activated by aldosterone via the RAAS pathway (i.e. Aldosterone activates serum and glucocorticoid-regulated kinase (SGK)-1; SGK-1 phosphorylates and inactivates Nedd4-2 that cannot bind with ENaC preventing its degradation). However, in Liddle syndrome mutated epithelial Na+ channels cannot bind with Nedd4-2 preventing its degradation and causing its increased activation.

Presents with hypertension, hypokalemia, and metabolic alkalosis; Laboratory parameters show low plasma aldosterone and low renin activity.

Management:- Epithelial Na+ channel blockers i.e. ENaC blockers (e.g. Amiloride); Amiloride also is useful for lithium-induced nephrogenic diabetes insipidus as it blocks Li+ transport into collecting tubule cells. 

Iron deficiency anemia (IDA)

Vignette says a 35 year old woman presents to her primary care physician with a history of fatigue and generalized weakness over the past 6 months; She also complains of shortness of breath with mild physical exertion; Over the last few weeks, she has also developed cravings for ice and eats ice frequently; She is vegetarian by diet; Additionally, she has been experiencing rectal bleeding for the past several months and describes blood being present on the toilet paper after bowel movements and also on the surface of the stool; She denies any pain during bowel movements but has occasional anal itching and discomfort; She has a history of chronic constipation and has been straining during bowel movements for years; Per rectal examination (PRE) shows external hemorrhoids with mild rectal tenderness; Examination shows pallor in the skin and conjunctiva; There are no signs of lymphadenopathy or hepatosplenomegaly; CBC shows low hemoglobin and low MCV; Iron studies show ↓ferritin, ↑TIBC, ↓serum iron, ↓% saturation; Diagnosis?

Diagnosis is Iron deficiency anemia (IDA).

Iron deficiency anemia is defined as hemoglobin below two standard deviations of the mean for the age and gender of the patient.

Pathogenesis:- ↓iron →↓heme →↓hemoglobin → microcytic anemia

Etiologies are insufficient iron intake, decreased absorption, increased requirement or blood

loss.

Presents with features of anemia (i.e. pallor, fatigue, SOB, palpitations), koilonychia, and

pica; Associated with Plummer vinson triad (i.e. IDA, esophageal webs and dysphagia,

glossitis).

Diagnosis:-

1. CBC shows low hemoglobin, microcytic and hypochromic RBCs with ↑red cell distribution

width and MCV < 80.

2. Iron profiling shows ↓ferritin, ↑TIBC, ↓serum iron, ↓% saturation. ↑Soluble transferrin

receptor (STFR) is elevated in IDA as in IDA there is an increased number of transferrin

receptors as they try to acquire more iron to compensate for deficiency.

3. ↑ Free erythrocyte protoporphyrin.

4. Mentzer index >13 suggests IDA; Mentzer index is MCV/RBC (million/uL).

Management:-

1. Iron supplementation (e.g. oral, intravenous); oral iron (e.g. Ferrous sulfate) is given along

with vitamin C to facilitate iron absorption; Reticulocytes are the first of improvement in iron

deficiency anemia.

2. Treat the underlying cause.

Kawasaki disease

Vignette says a 5 year old female child presents to the emergency department with history of high grade fever and red eyes for 6 days; Examination shows red, cracked tongue, red lips, and a faint maculopapular rash initially on the trunk that has now spread to her limbs; Her palms and soles are red and swollen, and she has enlarged bilateral cervical lymph nodes; Laboratory studies show elevated inflammatory markers (i.e. elevated CRP and ESR); Echocardiography shows coronary artery aneurysms; Diagnosis?

Diagnosis is Kawasaki disease. 

Kawasaki disease (aka mucocutaneous lymph node syndrome) is an acute, self-limited medium vessel vasculitis of an unknown etiology commonly affecting children.

Fever for at least 5 days with any 4 out of the 5 “CRASH” features.
Conjunctivitis
Rash (polymorphous, non vesicular on trunk and extremities)
Adenopathy (i.e. bilateral non-suppurative cervical lymphadenopathy)
Strawberry tongue
Hands/Feet edema and erythema 

Diagnosis:-
1. CBC shows leukocytosis.
2. Inflammatory markers (e.g. CRP, ESR) are elevated.
3. Echocardiography shows coronary artery aneurysms.

Treatment:- Aspirin + IVIG is the mainstay of treatment and should be initiated within the first 10 days of fever onset; IVIG is given at 2 g/kg in a single infusion and high dose aspirin is given at 80–100 mg/kg/day during the acute phase of the disease; The dose is gradually reduced to 3–5 mg/kg/day when the patient has been afebrile for over 48-72 hours.

Complication:- Coronary artery aneurysms and Myocardial infarction.

Atrial fibrillation

Vignette says a 55 year old female presents to the emergency department with a sudden onset of palpitations that started 30 minutes ago; She describes the sensation as her "heart racing" and feels lightheaded and dizziness but denies chest pain, shortness of breath or syncope; She states that she had similar episodes in the past that resolved spontaneously; She has a history of coronary artery disease; Vital signs show pulse rate of 180 beats/min, blood pressure of 110/70 mm of Hg, respiratory rate of 16 breaths/min, oxygen saturation of 96% in RA and temperature of 98.2 F; Laboratory studies show CBC, serum electrolytes, BMP, TSH and HbA1C within normal limits; ECG shows absent P waves, irregularly irregular rhythm (i.e. irregular R-R interval) and narrow QRS complexes; Transesophageal echocardiography shows thrombus in the left atrium; Diagnosis?

Diagnosis is Atrial fibrillation. 

Atrial fibrillation

Types:- 
1. Paroxysmal AFib:- Episodes of AFib shorter than 7 days, either self terminated or cardioverted (usually self terminated within 48 hours, often triggered in pulmonary veins). 2. Persistent AFib:- Episodes of AFib longer than 7 days, either self terminated or cardioverted. 
3. Long standing persistent AFib:- AFib lasting more than 1 year and rhythm control strategy is being adopted. 
4. Permanent AFib:- Episodes of AFib where no more rhythm strategy is adopted (i.e. as the rhythm is unresponsive). 

Presents with palpitations, SOB, syncope, and features of underlying conditions (e.g. stroke, sepsis, thyrotoxicosis). 

Causes:- 
1. Ischemic heart disease 
2. HTN 
3. Thyrotoxicosis 
4. Mitral stenosis or mitral regurgitation 
5. Alcohol 
6. OSA 

Diagnosis:- 
1. ECG shows absent P waves, irregularly irregular rhythm (i.e. irregular R-R interval), narrow QRS complex and tachycardia. 
2. Echocardiography (TEE or TTE) is done prior to cardioversion to prevent embolic stroke. 
3. Cardiac Monitor
4. EPS

Management:- 
1. Rate control:- Beta blockers (e.g. metoprolol, carvedilol, atenolol), non-dihydropyridine CCBs (e.g. verapamil, diltiazem) and Digoxin (in patients with CHF).
2. Rhythm control:- Pharmacological cardioversion (e.g. ibutilide, amiodarone, flecainide) or electrical cardioversion (DC 200J biphasic); It helps to return to sinus rhythm; Immediate cardioversion is deployed if the AFib has been present for less than 48 hours or the patient are hemodynamically unstable whereas delayed cardioversion is deployed if the AFib has been present for more than 48 hours and the patient are hemodynamically stable. 

What are the options for cardioversion for new-onset atrial fibrillation or atrial fibrillation of uncertain duration? 
· TEE prior to cardioversion while on effective anticoagulation with at least 4 weeks of therapeutic anticoagulation to follow (continue indefinitely if suggested by stroke risk).
· Alternatively, may therapeutically anticoagulate for at least 3 weeks prior to cardioversion and continue for at least 4 weeks afterwards, in lieu of TEE.

3. Anticoagulation:- Warfarin, DOACs (e.g. apixaban, rivaroxaban); CHA2DS2VASc is a clinical tool for prescribing anticoagulants in patients with nonvalvular atrial fibrillation; Congestive heart failure (1), Hypertension (1), Age ≥75 years (2), Diabetes (1), Stroke/TIA (2), Vascular disease e.g. previous myocardial infarction or peripheral arterial disease (1), Age 65-74 years (1), Sex category female (1). In non-valvular AFib, warfarin or Novel oral anticoagulants (NOACs) is indicated when CHA2DS2-VASc score ≥2 in men and ≥3 in women and should be considered CHA2DS2-VASc score >1 and >2 in men and women respectively. In valvular AFib, warfarin should be considered and targeted INR should be 2-3. 

4. Percutaneous ablation of pulmonary veins (i.e. pulmonary vein isolation) is first line for symptomatic paroxysmal atrial fibrillation. Catheter ablation for atrial fibrillation in patients with heart failure was associated with a significantly lower rate of a composite end point of death from any cause or hospitalization for worsening heart failure than was medical therapy (i.e. CASTLE HTx TRIAL).

5. Percutaneous left atrial appendage occlusion (if patients are contraindicated for long term anticoagulation therapy) i.e. Watchman, Watchman-FLX and Amlet devices. Percutaneous left atrial appendage occlusion is recommended in AF patients with a risk of stroke who have contraindications to long term anticoagulation. For high bleeding risk (HAS-BLED is greater than or equal to 3 if DOAC contraindicated.

6. Surgical ablation in patients with concomitant plan for cardiac surgery (e.g.maze procedure).
HAS-BLED score monitors a patient’s risk of major bleeding whilst on anticoagulation (i.e. Bleeding risk associated with anticoagulation); H - Hypertension, A - Abnormal renal and liver function, S - Stroke, B - Bleeding, L - Labile INRs (whilst on warfarin), E - Elderly, D - Drugs or alcohol; HAS-BLED score ≥ 3 (indicates high risk of bleeding).

Figure:- Management Guidelines of Atrial Fibrillation

Heart failure with reduced ejection fraction (HFrEF)

Vignette says a 68 year old male with a history of hypertension, diabetes mellitus and coronary artery disease presents to the emergency department with progressive onset of shortness of breath over the past 2 weeks; He also reports increasing fatigue, orthopnea (i.e. difficulty breathing when lying flat), paroxysmal nocturnal dyspnea (i.e. waking up at night feeling short of breath) and bilateral leg swelling up to the knee; He also reports of unintentional weight gain of 2 kg in the past 4 weeks; He has a history of hypertension, diabetes mellitus and coronary artery disease and takes medications for hypertension, diabetes and dyslipidemia; Examination shows jugular venous distension, 2 + pitting edema; On auscultation bilateral crackles/rales along with S3 heart sound are heard; CXR shows cardiomegaly with bilateral pleural effusions; Laboratory studies show elevated BNP & NT pro BNP, elevated BUN & creatinine and hyponatremia; Echocardiogram shows dilated left ventricle, left ventricular ejection fraction (LVEF) of 35%, and enlarged left atrium; Diagnosis?

Diagnosis is Heart failure with reduced ejection fraction (HFrEF).

The American College of Cardiology (ACC) defines Heart Failure with Reduced Ejection Fraction (HFrEF) as a clinical syndrome characterized by:- 

1. Symptoms and/or signs of heart failure. 

2. Reduced left ventricular ejection fraction (LVEF) ≤ 40%. 

3. Elevated natriuretic peptides (e.g. BNP or NT-proBNP).

Diagnosis:­-

1. CBC, Serum electrolytes, Troponins, BNP/NT pro BNP, RFT, and LFT; (BNP>400 pg/mL, NT pro BNP> 450mg/dL if < 50 years of age, NT pro BNP> 900mg/dL if 50-74 years of age and NT pro BNP> 1800mg/dL if > 75 years of age indicates acute heart failure).

2. Chest x ray shows pulmonary edema, cardiomegaly, Kerley B lines and pleural effusion. 

3. ECG shows LVH, atrial enlargement, condition abnormalities (e.g. LBBB, RBBB), ischemic changes, and arrhythmias (e.g. atrial fibrillation, sinus tachycardia, premature ventricular ectopic, ventricular tachycardia).

4. Echocardiography shows reduced left ventricular ejection fraction, regional wall motion abnormalities, dilated LV & LA and valvular dysfunction.

5. Radionuclide ventriculography.

6. Cardiac MRI.

7. Coronary angiography.

Management of chronic HFrEF:-

1. ACE-i (e.g. Enalapril, Lisinopril) /ARBs (e.g. losartan, valsartan, telmisartan)/ ARNI (e.g. sacubitril-valsartan); The PARADIGM- HF showed that Sacubitril/valsartan is superior to enalapril in reducing mortality and HF hospitalizations.

2. Beta blockers (e.g. Metoprolol, Carvedilol).

3. MRA (e.g. Spironolactone); The RALES trial (Randomized Aldactone Evaluation Study) showed that spironolactone significantly reduced mortality and hospitalizations in patients with severe HFrEF (LVEF ≤ 35%), particularly those with symptomatic heart failure.

4. SGLT2i (e.g. empagliflozin. Dapagliflozin); The DAPA-HF trial showed that Dapagliflozin significantly improved outcomes in HFrEF patients (i.e. reduced CV death and HF hospitalization), even in those without diabetes.

5. Diuretics (e.g. Furosemide, Torsemide).

6. Hydralazine and Nitrates (decreases mortality and morbidity in HFrEF among African Americans, with NYHA class III-IV HF receiving optimal medical therapy (OMT) with ACEi and beta-blockers). 

7. Adjunctive therapies:- Anticoagulation (patients with AFib); ivabradine (HR >70 bpm on maximally tolerated beta blocker therapy); Iron therapy (serum ferritin <100, TSAT<20%), and Digoxin (decrease hospitalization of HFrEF).

8. Inotropes (e.g. Dobutamine, Milrinone) as a bridge therapy for cardiac transplantation or Ventricular Assist Devices (e.g. IABP, impella, tandem heart and ECMO) in patients with stage D HF refractory to Guideline Directed Medical Therapy (GDMT). 

9. CRT (EF< 35% and QRS > 130 ms). 

10. ICD (EF< 35% and QRS < 130 ms). 

11. Ventricular assist device (VAD). 

12. Heart transplantation.

Figure:- Tretament algorithm of HFrEF (ACC/AHA 2022 Guideline)

Admit to hospital for management of acute decompensated heart failure and includes oxygen therapy via noninvasive ventilation (i.e. CPAP/BiPAP), diuretics (e.g. furosemide), vasodilators (e.g. nitroglycerin) and inotropes (e.g. dobutamine, milrinone).

Acute pericarditis

Vignette says 30 year old male presents to the emergency department with central chest pain, which is aggravated by cough, inspiration and relieved by leaning forward, since the past few days; He also had fever, myalgia, sore throat for which he took analgesics from local pharmacy 2 weeks back and was gradually resolved; On auscultation pericardial friction rub is heard over the left parasternal region; Laboratory studies show increased CRP and ESR with normal cardiac troponins; ECG shows diffuse ST elevation and PR depression; Diagnosis? 

Diagnosis is acute viral pericarditis. 

Etiologies:-
1. Viral/idiopathic (80-90%): Coxsackievirus, influenza
2. Autoimmune: SLE, RA, post-MI (Dressler's syndrome)
3. Bacterial: TB (fibrinous), purulent (staph/strep)
4. Malignancy:-Lung/breast cancer metastases

Clinical Features:-
1. Severe retrosternal chest pain, pleuritic (aggravated by inspiration and cough), positional (worse when supine & relieved by sitting or leaning forward) that radiates to back, left ridge of trapezius, and neck. 
2. Pericardial friction rub (produced by the movement of the inflamed pericardial layers against one another).
3. Dyspnea.
4. Mild grade fever and myalgias (if viral etiology).

Diagnosis:-
1. ECG shows diffuse ST elevation and PR depression. 
2. Echocardiogram is used to assess for complications of acute pericarditis (effusion or tamponade); Isolated pericarditis shows normal in echocardiography. 
3. CT/MRI.
4. Inflammatory biomarkers (e.g. CRP, ESR) are elevated and Cardiac Biomarkers (usually negative, positive indicates concurrent myocarditis).

Management:-
1. First-line Therapy: NSAIDs (e.g. ibuprofen) + Colchicine along with PPI's cover. 
2. Refractory Cases: Corticosteroids (prednisone 0.5 mg/kg/day, taper over 4 weeks): Reserve for autoimmune pericarditis. Avoid in viral cases (↑ recurrence risk).

Deep venous thrombosis

Vignette says a 50 year old male presents to the emergency department with chief complaints of right calf pain and selling on the 3rd postoperative day; He recently underwent open cholecystectomy for acute cholecystitis 3 days back; He has a history of hypertension for which he takes amlodipine; Examination shows right calf tenderness on palpation; Vital signs show blood pressure of 120/80 mm of Hg, pulse rate of 88 bpm, respiratory rate of 18 breaths/min, oxygen saturation of 92% in RA and temperature of 97.9 F; D-dimer is positive; Duplex ultrasound of the right lower extremity shows thrombus, filling defects and lack of compressibility; Diagnosis?

Diagnosis is Deep venous thrombosis (DVT).

Presents with calf pain, tenderness and swelling; The patient might develop low grade fever, acute onset SOB, tachycardia, tachypnea and pleuritic chest pain if pulmonary embolism occurs secondary to deep venous thrombosis; Homans's sign is positive (i.e. calf pain at dorsiflexion of the foot).

Risk factors:-
1. Stasis
2. Endothelial injury
3. Hypercoagulability

Wells Score for DVT (used to stratify the likelihood of DVT):- A score of 3 or more suggests a high likelihood of DVT, whereas a score of 1 or 2 indicates moderate probability and a score of 0 suggests low likelihood.

Diagnosis:-
1. D-dimer is positive.
2. Duplex ultrasound of the lower extremity shows filling defects, lack of compressibility, thrombus and dilated veins.

Management:-
1. Anticoagulation (e.g. LMWH) followed by warfarin or direct oral anticoagulants (e.g. apixaban, rivaroxaban).
2. Compression stockings to prevent post-thrombotic syndrome and reduce swelling.
3. Thrombolytics (Symptomatic iliofemoral DVT).
4. IVC filters are indicated if anticoagulation is contraindicated or if emboli are occurring despite adequate anticoagulation.
5. Evaluate for underlying risk factors (e.g. malignancy, thrombophilia).
6. Prevention strategies of DVT includes:-
a. Pharmacologic: Prophylactic LMWH or fondaparinux. 
b. Mechanical: Sequential compression devices (SCDs) and graduated compression stockings. 
c. Early ambulation post-surgery is also an important strategy to reduce stasis.

Giant cell arteritis (GCA)

Vignette says a 55 year old female presented to the neurology clinic with a history of headache in the right temporal region for 7 days; This morning, she experienced sudden episode of blurry vision in her right eye with spontaneous improvement in 15-20 minutes ; She also reports of pain and stiffness in the bilateral shoulders, scalp tenderness while combing hair, jaw claudication with chewing, fatigue, weight loss and mild fever over the past 6 months; Vital signs show blood pressure of 130/80 mm of Hg, pulse rate of 88 bpm, respiratory rate of 18 breaths/min, oxygen saturation of 98% in RA and temperature of 99.9 F; Examination shows tender, thickened right temporal artery with weak pulsation on palpation; Neurological examination is normal; Laboratory studies show ESR of 100 mm/hr, CRP of 75 mg/L; Temporal artery biopsy shows granulomatous inflammation with giant cells and intimal fibrosis; CT angiography shows arterial wall thickening and luminal narrowing of the right carotid artery; Diagnosis?

Diagnosis is Giant cell arteritis (GCA). 

Giant cell arteritis (GCA) is a large vessel vasculitis characterized by the granulomatous inflammation commonly affecting branches of the carotid artery; It is also known as temporal arteritis.

Presents with fever, fatigue, weight loss, unilateral temporal region headache, scalp tenderness, jaw claudication and vision problems; Associated with polymyalgia rheumatica.

The American College of Rheumatology (ACR) criteria for diagnosing temporal arteritis; three of the five criteria must be present to make the diagnosis which includes:-
1. Age greater than or equal to 50 at the onset of symptoms.
2. New onset headache.
3. Temporal artery abnormalities such as tenderness of the superficial artery or decreased pulsation.
4. ESR greater than or equal to 50 mm/hr.
5. Abnormal artery biopsy, including vasculitis (i.e. predominance of mononuclear cell infiltration or granulomatous inflammation, or multinucleated giant cells).

Diagnosis:-
1. CBC shows anemia of chronic disease.
2. Inflammatory markers (i.e. ESR and CRP) are elevated; ESR >100 mm/hr.
3. Creatine kinase is normal.
4. Duplex sonography of the temporal artery shows a "halo sign" (i.e. a circumferential hypoechoic area around the artery).
5. Biopsy shows granulomatous inflammation with giant cells and intimal fibrosis.
6. CTA or MRA shows arterial wall thickening, luminal narrowing and stenosis, contrast enhancement of the vessel wall of the carotid artery.

Management:-
1. Aspirin is given to reduce ischemic complications.
2. Steroids (i.e. IV methylprednisolone is given prior to temporal artery biopsy in order to prevent blindness as giant cell arteritis can lead to irreversible blindness from ophthalmic artery occlusion (AION)); IV methylprednisolone 1g/day is given for 3 days, then switch to oral prednisone 40- 60 mg/day and gradually taper the prednisone.
3. Tocilizumab (monoclonal antibody against IL-6 receptor) is used in patients with relapsing or refractory disease or those needing to reduce corticosteroid use. 
4. Calcium, Vitamin D and Bisphophonates (for osteoporosis prevention).

Graves disease

Vignette says a 38 year old female presents to her primary care physician with a 3 month history of weight loss despite good appetite, palpitations, and difficulty sleeping; She also reports of feeling increasingly anxious and has noticed a tremor in her hands; Vital signs shows heart rate of 110 beats per minute, and blood pressure of 140/80 mmHg; Examination shows exophthalmos (bulging eyes), a diffusely enlarged, non-tender thyroid, and a fine tremor in her hands; Thyroid function tests show low TSH and high free T4 and free T3 levels; Serology shows positive thyroid-stimulating immunoglobulin (TSI); Radioactive iodine uptake shows diffuse uptake; Diagnosis? 

Diagnosis is Graves disease. 

Graves disease is an autoimmune disease that occurs due to autoantibodies against TSH receptors of the thyroid gland, causing overproduction of thyroid hormone. It is the most common cause of hyperthyroidism in the United States.

Clinical features:-

1. Diffuse, enlarged thyroid glands; thyroid bruit is heard on auscultation.

2. Features of hyperthyroidism (i.e. anxiety, tremor, tachycardia, AFib, systolic HTN, weight loss

despite good appetite, hyperdefecation, heat intolerance, increased sweating, onycholysis, moist skin and fine hair).

3. Graves ophthalmopathy; It is characterized by upper eyelid retraction, lid lag, periorbital swelling, conjunctivitis, and bulging eyes (exophthalmos or proptosis).

4. Pretibial myxedema.

Diagnosis:-

1. Thyroid function test (TFT) shows low TSH and high fT3/fT4.

2. Anti thyroid receptor antibodies is positive (i.e. Thyroid stimulating immunoglobulins is positive).

3. Radioactive iodine uptake (RAIU) shows diffuse uptake.

4. Thyroid ultrasonography shows diffuse enlarged thyroid gland.

5. Histology shows follicular hyperplasia, intracellular colloid droplets, cell scalloping, a reduction in follicular colloid, and a patchy lymphocytic infiltration.

6. MRI of orbit for evaluating ophthalmopathy.

Management:-

1. Beta blockers are used (e.g. propranolol) for symptoms due to sympathetic overactivity.

2. Anti thyroid drugs are used  (e.g. methimazole, propylthiouracil) to block thyroid hormone synthesis and release; The recommended starting dose is 0.5–1.0 mg/kg/day for methimazole and 5–10 mg/kg/day for propylthiouracil. 

3. Radioactive iodine (RAI) ablation therapy.

4. Total or subtotal thyroidectomy.