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.