What’s the connection between lemon juice and disseminated candidiasis in my patient with illicit IV drug use?

Lemon juice is often used by IV drug users to help dissolve poorly water soluble street drugs, such as brown heroin or crack-cocaine, and may serve as a vehicle for Candida albicans infection. 1-3

Contamination of lemon juice (either from wild lemons or from the plastic containers) is thought to occur from either the skin and/or oropharynx of the user.1  Other fruit juices such as orange juice as well as raspberry syrup have been implicated as a source of disseminated candidiasis in IV drug users.4

Experimental inoculation of lemons with small numbers of C. albicans has demonstrated rapid growth of the organism at room temperature resulting in inadvertent injection of a large inoculum size. 2 Once inoculated directly into the blood stream, C. albicans disseminates and can present in many ways, including skin lesions, ocular lesions/endophthalmitis, and osteoarticular infections (eg, costochondral, hip joint, and vertebral infections).1  

So it is advisable to not only ask about what recreational drug is being injected but also what it is injected with!

Bonus Pearl: Did you know that although lemon juice is an excellent growth medium for C. albicans, it has bactericidal properties against Staphylococcus aureus and Pseudomonas aeruginosa? 1

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References

  1. Bisbe J, Miro JM, Latorre X, et al. Disseminated candidiasis in addicts who use brown heroin: report of 83 cases and review. Clin Infect Dis 1992;15:910-23. https://www.ncbi.nlm.nih.gov/pubmed/1457662
  2. Newton-John HGF, Wise K, Looke DFM. Role of the lemon in disseminated candidiasis of heroin abusers. Med j Aust 1984;140:780-81. https://onlinelibrary.wiley.com/doi/abs/10.5694/j.1326-5377.1984.tb132597.x?sid=nlm%3Apubmed
  3. Shankland GS, Richardson MD. Source of infection in candida endophthalmitis in drug addicts. Br J Ophthalmol 1986;292:1106-7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1954783/pdf/702.pdf
  4. Scheidegger C, Pietrzak J, Frei R. Methadone diluted with contaminated orange juice or raspberry syrup as a potential source of disseminated candidiasis in drug abusers. Eur J Clin Microbiol Infect Dis 1993;12:229-31. https://link.springer.com/article/10.1007/BF01967124
What’s the connection between lemon juice and disseminated candidiasis in my patient with illicit IV drug use?

Is my patient with gout at higher risk of cancer?

Although the association of gout with cardiovascular disease, chronic kidney disease, hypertension, diabetes mellitus or obesity is well known, increasingly number of epidemiologic studies support the association of gout with higher risk of malignancy. 1,2

A 2015 meta-analysis of 3 studies involving over 50,000 persons concluded that gout was an independent risk factor for cancer, particularly urological, gastrointestinal and lung cancers. 1

A population-based study of comorbidities in over 2 million persons in Sweden found that in addition to an increased risk of diabetes mellitus, hypertension, chronic heart failure, chronic kidney disease and alcohol abuse, gout was associated with increased risk of malignancy: odds ratio 1.3 (1.2-1.5) in men and 1.1 (1.1-1.2) in women. 2

Although serum uric acid has been considered to have anti-oxidant properties, a prospective study of over 28,000 women followed over a median of 15.2 years did not find high serum acid levels to be protective of cancer.3 In fact, uric acid levels > 5.4 mg/dL at the time of subject enrollment was independently associated with increased risk of total cancer mortality and deaths from a variety of malignant neoplasms, including those of breast, female genital organs, and nervous systems. 3 In a similar prospective study involving men, high uric acid levels (>6.7 mg/dL) were associated with increased risk of mortality from gastrointestinal, respiratory and intrathoracic organ malignancies. 4

Whether the observed association between gout and higher risk of malignancy is causal or due to the company that gout often keeps (eg, lifestyle) is unclear.

Fun fact: Did you know that among mammals, only humans, great apes and certain breeds of dogs (eg, Dalmation) produce elevated levels of uric acid in the urine and blood? 5

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References

  1. Wang W, Xu D, Wang B, et al. Increased risk of cancer in relation to gout: a review of three prospective cohort studies with 50,358 subjects. Mediators of Inflammation 2015, Article ID 680853, 6 pages. https://www.ncbi.nlm.nih.gov/pubmed/26504360
  2. Wandell P. Gout and its comorbidities in the total population of Stockholm. Preventive Medicine 2015; 81:387-91. ISSN 0091-7435. https://www.ncbi.nlm.nih.gov/pubmed/26500085
  3. Strasak AM, Rapp K, Hilbe W, et al. The role of serum uric acid as an antioxidant protecting against cancer: prospective study in more than 28000 older Austrian women. Ann Onc 2007;18:1893-97. https://www.ncbi.nlm.nih.gov/pubmed/17785768
  4. Strasak Am, Hilbe RK, Oberaingner W, et al. Serum uric acid and risk of cancer mortality in a large prospective male cohort. Cancer Causes Control 2007;18:1021-9. https://www.ncbi.nlm.nih.gov/pubmed/17665312
  5. Bannasch D, Safra N, Young A, et al. Mutations in the SLC2A9 gene cause hyperuriosuria and hyperuricemia in the dog. PLOS Genet 2008;4:e1000246. https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1000246&type=printable
Is my patient with gout at higher risk of cancer?

Why is my patient with systemic amyloidosis at higher risk of bleeding?

The major mechanism of bleeding tendency in primary systemic amyloidosis (AL) appears to revolve around amyloid deposit infiltration of the vasculature and musculature, leading to amyloid angiopathy, fragility, impaired vasoconstriction, tears and hemorrhage. 1,2 Other potential mechanisms include:

  • Presence of plasma inhibitors of fibrinogen conversion to fibrin
  • Deficiencies of factor X, IX and V due to their affinity for amyloid substance
  • Presence of circulating heparin-like anticoagulants
  • Uremic platelet dysfunction in the presence of renal involvement

In a study involving 36 patients with AL, ~30% had bleeding symptoms with alterations of 1 or more clotting tests found in ~85%: prolonged prothrombin time (PT) ratio (22%), activated partial thromboplastin time (aPTT) (65%) and thrombin time (85%).

Clinical manifestations of amyloidosis related to its bleeding diathesis include petechiae, ecchymoses, purpura (“raccoon eyes when periorbital), uncontrollable epistaxis, gingival bleeding, and gastrointestinal bleed or submucosal hematomas. 1-6

Due to its convenience and relative safety, a biopsy of abdominal fat or minor salivary glands is often initially performed for definitive diagnosis of amyloidosis, followed by biopsy of specific organs (eg, kidney, liver), if needed. 3,6

Due to the potential risk of bleeding complications, transjugular liver biopsy is preferred over percutaneous approach. This is because the liver capsule is not perforated with transjugular liver biopsy and if bleeding occurs, the blood returns directly into the venous system rather than into the peritoneum. 7-8 

Bonus Pearl: Did you know that AL amyloidosis is the most common type of systemic amyloidosis in western countries? This is because the incidence of the other major type of amyloidosis (AA), often related to chronic infections or inflammatory diseases, has been dropping in these countries.3

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References

  1. Gamba G, Montani N, Anesi E, et al. Clotting alterations in primary systemic amyloidosis. Haematologica 2000;85:289-92. https://moh-it.pure.elsevier.com/en/publications/clotting-alterations-in-primary-systemic-amyloidosis
  2. Marconcini LAL, Stewart FM, Sonntag L, et al. AL amyloidosis complicated by persistent oral bleeding. Case Reports in Hematology 2015, Article ID 981346. https://www.hindawi.com/journals/crihem/2015/981346/
  3. Desport E, Bridoux F, Sirac C, et al. AL Amyloidosis. Orphanet Journal of Rare Diseases 2012, 7:54. https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-7-54
  4. Yoshii S, Mabe K, Nosho K, et al. Submucosal hematoma is a highly suggestive finding for amyloid light-chain amyloidosis: Two case reports. W J Gastroenterol 2012;4:434-37. https://www.ncbi.nlm.nih.gov/pubmed/23125904
  5. Kon T, Nakagawa N, Yoshikawa F, et al. Systemic immunoglobulin light-chain amyloidosis presenting hematochezia as the initial symptoms. Clin J Gastroenterol 2016;9:243. http://europepmc.org/article/med/27318996
  6. Petre S, Shah IA, Gilani N. Review article:gastrointestinal amyloidosis-clinical features, diagnosis and therapy. Alim Pharmacol Ther 2008;27:1006-16. https://www.ncbi.nlm.nih.gov/pubmed/18363891
  7. Grant A, Neuberger J. Guidelines on the use of liver biopsy in clinical practice. Gut 1999;45(Suppl IV):IV1-IV11. https://www.ncbi.nlm.nih.gov/pubmed/10485854
  8. Dohan A, Guerrache Y, Boudiaf M, et al. Transjugular liver biopsy: Indications, technique and results. Diagnostic and Interventional Imaging 2014;95:11-15. https://www.ncbi.nlm.nih.gov/pubmed/24007769
Why is my patient with systemic amyloidosis at higher risk of bleeding?