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.

Supraventricular tachycardia (SVT)

Vignette says a 28 year old female presents to the emergency department with a sudden onset of palpitations that started 30 minutes ago while she was studying for an exam; She describes the sensation as her "heart racing" and feels lightheaded but denies chest pain, shortness of breath, or syncope; She states that she had similar episodes in the past that resolved spontaneously; She has no significant past medical history and takes no medications; She drinks 2–3 cups of coffee daily; 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; The patient appears anxious but is alert and oriented; ECG shows a narrow QRS complex tachycardia at 180 bpm with absent visible P waves in lead II; Diagnosis?

Diagnosis is Supraventricular tachycardia (SVT). Supraventricular tachycardia (SVT) is a tachyarrhythmia originating at or above the atrioventricular node and is defined by a narrow complex (QRS < 120 milliseconds) at a rate > 100 beats per minute (bpm).

Types:-

1. AV nodal reentry tachycardia (AVNRT)

2. Atrioventricular reentry tachycardia (AVRT)

3. Atrial tachycardia (AT)

Presents with symptoms such as palpitations, chest discomfort, dyspnea, dizziness, light-headedness, presyncope, syncope, or anxiety.

Diagnosis:-

1. ECG

2. Cardiac monitoring

3. EP studies

Treatment of SVT:- 

1. If the patient is hemodynamically unstable, consider synchronized cardioversion. 

2. If the patient is hemodynamically stable:- 

• Apply vagal maneuvers (e.g. carotid massage, ice water immersion, modified valsalva maneuver i.e. the modified Valsalva maneuver (mVm) has been shown to have a higher success rate in converting hemodynamically stable SVT to normal sinus rhythm (NSR) when compared to sVm (REVERT trial)).
• Pharmacological therapy includes adenosine, beta blockers (metoprolol), calcium channel blockers (verapamil, diltiazem).

3. Radiofrequency ablation. When to refer to ablation?

• Recurrent episodes despite medications.
• Medication intolerance
• High-risk occupations (pilots, commercial drivers)
• WPW syndrome

ECG of AVNRT shows sinus tachycardia, normal QRS complex (<120ms) complex and P wave inversion in leads II, III and aVF.

Figure:- ECG showing AVNRT

Testicular torsion

Vignette says a 21 year old male presents to the emergency department with a sudden onset of severe testicular pain, that started 6 hours ago while playing basketball; The pain is sudden in onset, severe in intensity and localized to the right testicle; He also reports nausea but no vomiting; Genital examination shows swollen, erythematous and tender right sided scrotum; Cremasteric reflex is absent; Vital signs show blood pressure of 110/80 mm of Hg, pulse rate of 88 bpm, respiratory rate of 16 breaths/min, oxygen saturation of 98% in RA and temperature of 96.7F; He has no significant medical or surgical history; Doppler ultrasonography shows absence of testicular blood flow; Diagnosis?

Diagnosis is testicular torsion.

Presents with acute onset severe testicular pain along with swollen, erythematous scrotum; Associated with congenital inadequate fixation of testis to tunica vaginalis → horizontal positioning of testes (“bell clapper” deformity); Prehn sign is negative (i.e. failure to relieve pain upon lifting the scrotum) and cremasteric reflex is absent (i.e. failure of the scrotal skin to retract upon palpation of the medial thigh).

Diagnosis:-

1. Doppler ultrasonography shows absence of testicular blood flow.

Management:-

1. Surgical detorsion and fixation (orchiopexy) within 6 hours; Manual detorsion (if immediate surgery is not available.

2. Orchiectomy (if testis is not viable).

Osteopetrosis

Vignette says a 7 year old male child presents to pediatrician with chief complaints frequent bone fractures, recurrent infections and visual impairment; His mother also reports that he has had multiple fractures, even with minimal trauma over the past few years; His mother also reports that he has had several episodes of pneumonia and ear infections requiring hospitalizations in the past; Examination shows pale conjunctiva, macrocephaly with frontal bossing and hepatosplenomegaly; Neurological examination shows decreased visual acuity and decreased hearing; Complete blood count (CBC) shows pancytopenia; X-ray shows diffuse osteosclerosis; Bone marrow biopsy shows dense, sclerotic bone with little marrow space; Diagnosis?

Diagnosis is Osteopetrosis.

Osteopetrosis (also known as "marble bone disease"), is a genetic disorder characterized by defective osteoclast function leading to impaired bone resorption and the accumulation of abnormally dense bones.

Pathophysiology:- Deficiency of carbonic anhydrase → failure to resorb bone by osteoclasts (i.e. poor osteoclast function due to type II carbonic anhydrase deficiency). 

Clinical features:- 
1. Thick bones which fracture easily (i.e. pathologic fractures).
2. Vision and hearing impairment.
3. CN deficits and hydrocephalus (due to narrowing of foramen in the brain).
4. Type II RTA (i.e. proximal RTA).
5. Pancytopenia and hepatosplenomegaly (due to bone expansion leading to bone marrow narrowing and extramedullary hematopoiesis).

Diagnosis:- 
1. CBC shows pancytopenia.
2. X-ray shows diffuse osteosclerosis (aka “marble bone disease”). 
3. Elevated tartrate-resistant acid phosphatase (TRAP). 
4. Genetic testing shows mutation in the CLCN7 or TCIRG1 gene.
5. Bone marrow biopsy shows dense, sclerotic bone with little marrow space.

Management:- 
1. Supportive measures include pain management, physical therapy, and management of recurrent infections.
2. Calcium and vitamin D supplementation.
3. Erythropoietin or blood transfusions for anemia.
4. IFN-gamma (activates osteoclasts). 
5. Bone marrow transplantation is the only curative treatment.

Spontaneous bacterial peritonitis

Vignette says a 55 year old male with a history of cirrhosis and ascites due to chronic alcohol use presents to the emergency department with chief complaints of diffuse abdominal pain, vomiting, and a mild low grade fever over the past two days; He also reports of fatigue and increasing confusion; Vital signs show blood pressure of 100/60 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; Abdominal examination shows distended abdomen with shifting dullness, mild diffuse tenderness, and hypoactive bowel sounds on auscultation; CBC shows WBC count of 14,000 cells/mm3, serum creatinine of 1.8 mg/dL (normal range is 0.7mg/dL-1.3mg/dL), serum albumin of 2.1g/dL (normal range is 3.5-5.5 g/dL); Paracentesis with ascitic fluid absolute neutrophil count is 380 cells/mm3; Diagnosis?

Diagnosis is Spontaneous bacterial peritonitis (SBP).

Spontaneous bacterial peritonitis (SBP) is defined as the infection of the ascitic fluid.

Presents with fever, diffuse abdominal pain in patients with liver cirrhosis along with ascitic fluid absolute neutrophil count (ANC) > 250 cells/mm3.

Etiologic agents are Escherichia coli (most common), Klebsiella, Streptococcus pneumoniae.

Diagnosis:-

1. Paracentesis with ascitic fluid absolute neutrophil count (ANC) > 250 cells/mm3.

2. Gram staining and culture of the ascitic fluid.

Management:-

1. 3rd generation cephalosporins (e.g. cefotaxime, ceftriaxone).

2. Albumin infusion to prevent kidney failure.

3. Prophylactic ciprofloxacin or trimethoprim/sulfamethoxazole is used to prevent SBP if ascitic fluid albumin is low. 

Normal pressure hydrocephalus (NPH)

Vignette says a 75 year old male with a history of hypertension and diabetes presents to the neurology clinic with complaints of difficulty walking, memory problems and urinary incontinence over the past year; His wife notes that he has been more forgetful recently, often misplacing items and repeating conversations, although he still recognizes family members and can performs daily tasks; He wife also notes that recently, he started urinating on himself frequently before reaching the bathroom; The patient exhibits a slow, broad-based gait with difficulty initiating step movement, and a tendency to fall forward (also known as "magnetic gait"); There are no signs of increased intracranial pressure (e.g. headache, vomiting, papilledema); Examination shows normal deep tendon reflexes with no focal neurologic deficits; CT scan of head shows enlargement of the lateral ventricles without significant cortical atrophy.; Lumbar puncture shows normal opening pressure; Diagnosis?

Diagnosis is normal pressure hydrocephalus. 

Normal pressure hydrocephalus (NPH) is a chronic dilatation of the cerebral ventricles with a normal lumbar puncture opening pressure.

Pathophysiology:- Failure of reabsorption of CSF by the arachnoid granulations.

Presents with urinary incontinence, ataxia, dementia (i.e. "wet, wobbly, and wacky").

The patient shows significant improvement in symptoms after a CSF removal of about 30-50 mL.

Diagnosis:-
1. Lumbar puncture shows normal opening pressure with large volume lumbar tap. 
2. CT scan of head shows enlargement of the lateral ventricles without significant cortical atrophy.
3. MRI shows ventricular enlargement disproportionate to cortical atrophy.

Management:- Ventriculoperitoneal (VP) shunt.

Pneumocystis jirovecii

Vignette says a 33 year old male with a known history of HIV presents to the emergency department with a 7 days history of progressive shortness of breath, dry cough and fever; His CD4 count is 90 cells/μL despite being on antiretroviral therapy (ART); Vital signs show blood pressure of 110/70 mm of Hg, pulse rate of 108 bpm, respiratory rate of 22 breaths/min, oxygen saturation of 92% in RA and temperature of 100.9 F;  Lung auscultation reveals bilateral crackles; There is no evidence of peripheral edema or lymphadenopathy; CBC shows white blood cell count of 6,000 cells/mm3 with a mild lymphopenia; Chest X-ray shows bilateral diffuse reticulonodular infiltrates and CT scan of the chest shows ground-glass opacities, especially in the perihilar regions; ABG analysis shows pH of 7.48, PaCO2 of 30 mmHg, PaO2 of 50 mmHg and HCO3- of 22mEq/L; Microscopic examination of bronchoalveolar lavage (BAL) with silver stain shows disc shaped yeast; Diagnosis?

Diagnosis is Pneumocystis jirovecii.

Pneumocystis jirovecii pneumonia is caused by Pneumocystis jirovecii.

Etiologies:-

1. AIDS (i.e. CD4 < 200 cells/μL)

2. Immunosuppressive medications (e.g. chronic glucocorticoids, immunosuppressant agents)

Presents with fever, dyspnea and dry cough.

Diagnosis:-

1. Chest x-ray shows diffuse bilateral reticulonodular infiltrates.

2. LDH is elevated.

3. Microscopic examination of BAL with silver stain shows disc shaped yeast.

Management:-

1. Trimethoprim-sulfamethoxazole + Steroids; Indications for steroids in Pneumocystis

pneumonia is A-a gradient >35 mm Hg, or PaO2 <70, or SaO2 <92% in RA.

2. ART therapy.

Patients with AIDS (i.e. CD4 <200 cells/μL) and those on chronic glucocorticoid therapy

generally receive primary prophylaxis against Pneumocystis jirovecii pneumonia with

trimethoprim-sulfamethoxazole.

Guillain-Barré Syndrome (GBS)

Vignette says a 42 year old male presents to the emergency department with a progressive weakness in his both legs along with tingling sensation in his feet over the past 4 days; He also suggests that the weakness has gradually spread upwards in past 24 hours, now affecting his arms and causing difficulty in swallowing; He states that he had developed bloody diarrhea 2 weeks back after consumption of poultry products; On examination he has bilateral lower limb weakness with MRC grade of 3/5 in both limbs along with absent deep tendon reflexes in both knees and ankles; CSF shows elevated protein with normal cell count; Electrophysiologic studies show prolonged latency, decreased motor nerve conduction velocities and amplitude; MRI of the brain and spinal cord is normal; Serology shows Campylobacter jejuni infection; Diagnosis?

Diagnosis is GBS following campylobacter infection.

Guillain-Barré Syndrome (GBS) is an autoimmune demyelinating disorder of peripheral nervous system that usually following gastrointestinal or respiratory infections; Molecular mimicry between microbe and nerve antigens; Commonly associated with Campylobacter jejuni, Mycoplasma pneumoniae, cytomegalovirus, Epstein Barr, influenza A, Zika, HIV.

Presents with bilateral symmetric progressive, ascending flaccid paralysis or weakness of limbs, decreased deep tendon reflexes and distal numbness or dysesthesias (i.e. feeling of pins and needles) of extremities.

Diagnosis:-
1. CSF shows elevated protein with normal cell count (i.e. albuminocytologic dissociation).
2. Electrophysiologic studies (EMG/NCV) show demyelination in peripheral nerves (i.e. prolonged latency, decreased motor nerve conduction velocities and amplitude).
3. MRI of the brain and spinal cord is usually normal or shows enhancement of anterior nerve roots/cauda equina.
4. Spirometry (i.e. FVC) is used to assess pulmonary function. 

Treatment:-
1. Intravenous immunoglobulin (i.e. IVIG) or Plasmapheresis is the mainstay of treatment. 
2. Supportive measures like DVT prophylaxis, Respiratory monitoring and Physical therapy.

Figure:- Guillain-Barré Syndrome

Third degree heart block

Vignette says a 60 year old male presents to the emergency department with complaints of fatigue, dizziness, lightheadedness and occasional near syncopal episodes over the past few days; He also complains of intermittent chest pain and shortness of breath on exertion since the past few days; He has a history of hypertension and takes losartan daily; On examination JVP shows cannon a waves; Vital signs show pulse rate of 35 beats/min which is slow and regular in nature, blood pressure of 110/70 mm of Hg, respiratory rate of 16 breaths/min, oxygen saturation of 96% in RA and temperature of 97.2 F; ECG shows wide QRS complex with no relation between P waves and QRS complexes however R-R intervals and P-P intervals are constant; Diagnosis?

Diagnosis is Third degree heart block.

Third degree heart block is characterized by a complete loss of communication between atria and ventricles (i.e. no impulse from atria passes through the AV node to the ventricles); JVP shows cannon A waves; ECG shows a wide QRS complex (ventricular escape rhythm) or narrow QRS complex (junctional escape rhythm) with no relation between P waves and QRS complexes however R-R intervals & P-P intervals are constant.

Causes:-

1. Idiopathic fibrosis or degeneration of the conducting system (i.e. Lev's disease)

2. Autoimmune disorders (e.g. SLE, systemic sclerosis)

3. Inflammatory conditions (e.g. myocarditis, Lyme disease, acute rheumatic fever)

4. Infiltrative myocardial disease (e.g. hemochromatosis, sarcoidosis, amyloidosis)

5. Electrolyte imbalance (e.g. hyperkalemia)

6. AV nodal blocking agents (e.g. beta-blockers, non-dihydropyridine calcium channel blockers, digitalis, adenosine, or amiodarone)

7. Anterior wall MI (due to extensive necrosis of the septum and conduction tissue i.e. His-Purkinje system)

8. Inferior wall MI (since right coronary artery supplies the AV node (i.e. right coronary dominant))

Presents with generalized fatigue, tiredness, lightheadedness, dizziness, chest pain, shortness of breath, near syncope and syncope. 3rd degree heart block is associated with polyuria (AV dissociation occurs as there is complete loss of communication between atria and ventricles in 3rd degree heart loss; this causes huge stretch in atrium leading to release of ANP which subsequently causes diuresis and polyuria).

Diagnosis:- 

1. ECG shows a wide QRS complex (ventricular escape rhythm) or narrow QRS complex (junctional escape rhythm) with no relation between P waves and QRS complexes however R-R intervals & P-P intervals are constant.

2. Electrophysiology study.

Treatment:-

1. Temporary pacemakers (i.e. transcutaneous or transvenous pacing to increase the ventricular rate). 

2. Insertion of permanent pacemaker (PPM).

3. Treat the underlying cause and stop the offending agents.

Figure:- ECG showing 3rd degree heart block