Should I consider acute acalculous cholecystitis in my elderly ambulatory patient admitted with right upper quadrant pain?

Short answer: Yes! Although we usually associate acute acalculous cholecystitis (AAC) with critically ill patients (eg, with sepsis, trauma, shock, major burns) in ICUs, AAC is not as rare as we might think in ambulatory patients. In fact, a 7 year study of AAC involving multiple centers reported that AAC among outpatients was increasing in prevalence and accounted for 77% of all cases (1)!

 
Although the pathophysiology of ACC is not fully understood, bile stasis and ischemia of the gallbladder either due to microvascular or macrovascular pathology have been implicated as potential causes (2). One study found that 72% of outpatients who developed ACC had atherosclerotic disease associated with hypertension, coronary, peripheral or cerebral vascular disease, diabetes or congestive heart failure (1). Interestingly, in contrast to calculous cholecystitis, “multiple arterial occlusions” have been observed on pathological examination of the gallbladder in at least some patients with ACC and accordingly a name change to “acute ischemic cholecystitis” has been proposed (3).

 
AAC can also complicate acute mesenteric ischemia and may herald critical ischemia and mesenteric infarction (3). The fact that cystic artery is a terminal branch artery probably doesn’t help and leaves the gallbladder more vulnerable to ischemia when arterial blood flow is compromised irrespective of the cause (4).

 
Of course, besides vascular ischemia there are numerous other causes of ACC, including infectious (eg, viral hepatitis, cytomegalovirus, Epstein-Barr virus, Salmonella, brucellosis, malaria, Rickettsia and enteroviruses), as well as many non-infectious causes such as vasculitides and, more recently, check-point inhibitor toxicity (1,5-8).

 
Bonus Pearl: Did you know that in contrast to cholecystitis associated with gallstones (where females and 4th and 5th decade age groups predominate), ACC in ambulatory patients is generally more common among males and older age groups (mean age 65 y) (1)?

 

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References
1. Savoca PE, Longo WE, Zucker KA, et al. The increasing prevalence of acalculous cholecystitis in outpatients: Result of a 7-year study. Ann Surg 1990;211: 433-37. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1358029/pdf/annsurg00170-0061.pdf
2. Huffman JL, Schenker S. Acute acalculous cholecystitis: A review. Clin Gastroenterol Hepatol 2010;8:15-22. https://www.cghjournal.org/article/S1542-3565(09)00880-5/pdf
3. Hakala T, Nuutinene PJO, Ruokonen ET, et al. Microangiopathy in acute acalculous cholecystitis Br J Surg 1997;84:1249-52. https://bjssjournals.onlinelibrary.wiley.com/doi/abs/10.1046/j.1365-2168.1997.02775.x?sid=nlm%3Apubmed
4. Melo R, Pedro LM, Silvestre L, et al. Acute acalculous cholecystitis as a rare manifestation of chronic mesenteric ischemia. A case report. Int J Surg Case Rep 2016;25:207-11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4941110/
5. Aguilera-Alonso D, Median EVL, Del Rosal T, et al. Acalculous cholecystitis in a pediatric patient with Plasmodium falciparum infection: A case report and literature review. Ped Infect Dis J 2018;37: e43-e45. https://journals.lww.com/pidj/pages/articleviewer.aspx?year=2018&issue=02000&article=00020&type=Fulltext  
6. Kaya S, Eskazan AE, Ay N, et al. Acute acalculous cholecystitis due to viral hepatitis A. Case Rep Infect Dis 2013;Article ID 407182. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3784234/pdf/CRIM.ID2013-407182.pdf
7. Simoes AS, Marinhas A, Coelho P, et al. Acalculous acute cholecystitis during the course of an enteroviral infection. BMJ Case Rep 2013;12. https://casereports.bmj.com/content/12/4/e228306
8. Abu-Sbeih H, Tran CN, Ge PS, et al. Case series of cancer patients who developed cholecystitis related to immune checkpoint inhibitor treatment. J ImmunoTherapy of Cancer 2019;7:118. https://jitc.biomedcentral.com/articles/10.1186/s40425-019-0604-2

 

 

Should I consider acute acalculous cholecystitis in my elderly ambulatory patient admitted with right upper quadrant pain?

My patient with sepsis and bacteremia has an extremely high serum Creatine kinase (CK) level. Can his infection be causing rhabdomyolysis?

 Absolutely! Although trauma, toxins, exertion, and medications are often listed as common causes of rhabdomyolysis, infectious etiologies should not be overlooked as they may account for 5% to 30% or more of rhabdomyolysis cases (1,2).

 

Rhabdomyolysis tends to be associated with a variety of infections, often severe, involving the respiratory tract, as well as urinary tract, heart and meninges, and may be caused by a long list of pathogens (1).  Among bacterial causes, Legionella sp. (“classic” pathogen associated with rhabdomyolysis), Streptococcus sp. (including S. pneumoniae), Salmonella sp, Staphylococcus aureus, Francisella tularensis have been cited frequently (3).  Some series have reported a preponderance of aerobic gram-negatives such as Klebsiella sp., Pseudomonas sp. and E. coli  (1,2).   Among viral etiologies, influenza virus, human immunodeficiency virus, and coxsackievirus are commonly cited (2,3).  Fungal and protozoal infections (eg, malaria) may also be associated with rhabdomyolysis (5).

 

So how might sepsis cause rhabdomyolysis? Several potential mechanisms have been implicated, including tissue hypoxemia due to sepsis, direct muscle invasion by pathogens (eg, S. aureus, streptococci, Salmonella sp.), toxin generation (eg, Legionella), cytokine-mediated muscle cell toxicity (eg, aerobic gram-negatives) as well as muscle ischemia due to shock (1,5).

 

Bonus Pearl: Did you know that among patients with HIV infection, infections are the most common cause (39%) of rhabdomyolysis (6)? 

 

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References

 

1. Kumar AA, Bhaskar E, Shantha GPS, et al. Rhabdomyolysis in community acquired bacterial sepsis—A retrospective cohort study. PLoS ONE 2009;e7182. Doi:10.1371/journa.pone.0007182. https://www.ncbi.nlm.nih.gov/pubmed/19787056.

2. Blanco JR, Zabaza M, Sacedo J, et al. Rhabdomyolysis of infectious and noninfectious causes. South Med J 2002;95:542-44. https://www.ncbi.nlm.nih.gov/pubmed/12005014

3. Singh U, Scheld WM. Infectious etiologies of rhabdomyolysis:three case reports and review. Clin Infect Dis 1996;22:642-9. https://www.ncbi.nlm.nih.gov/pubmed/8729203

4. Shih CC, Hii HP, Tsao CM, et al. Therapeutic effects of procainamide on endotoxin-induced rhabdomyolysis in rats. PLOS ONE 2016. Doi:10.1371/journal.pone.0150319. https://www.ncbi.nlm.nih.gov/pubmed/26918767

5. Khan FY. Rhabdomyolysis: a review of the literature. NJM 2009;67:272-83. http://www.njmonline.nl/getpdf.php?id=842

6. Koubar SH, Estrella MM, Warrier R, et al. Rhabdomyolysis in an HIV cohort: epidemiology, causes and outcomes. BMC Nephrology 2017;18:242. DOI 10.1186/s12882-017-0656-9. https://bmcnephrol.biomedcentral.com/track/pdf/10.1186/s12882-017-0656-9

My patient with sepsis and bacteremia has an extremely high serum Creatine kinase (CK) level. Can his infection be causing rhabdomyolysis?