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Cryptococcal Meningitis Infections in Lupus often Misdiagnosed

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Cryptococcal Meningitis Infections in Lupus often Misdiagnosed

Researchers writing in the journal Emerging Microbes & Infections find that 38 percent of patients with lupus-related cryptococcal meningitis are misdiagnosed.

The study, which appears in the Sept. 7 online issue of the journal, is based on a systematic review of data from two hospitals in China and nine literature databases. The final analysis included 38 articles involving 55 cases of cryptococcal meningitis in SLE patients.

The researchers found that the prevalence of cryptococcal meningitis in systemic lupus erythematosus patients was 0.5% primarily affecting adult women. A prednisone equivalent of more than 30 mg/day before infection was associated with higher mortality (odds ratio (OR)=9.69 (1.54, 60.73)). In all, 36.8–38.9% patients showed low lupus activity when they developed the crytococcal infection.

Microbial infections are one the most important causes of morbidity and mortality in systemic lupus erythematosus patients leading to death in 20–40% of cases, the Chinese researchers wrote.

The Risk of Life-Threatening Infections

The increased risk of developing life-threatening infections like cryptococcal meningitis is multifactorial. SLE patients using high dose steroids, frequent antibiotics or suffering from high SLE activity are at greater risk for infections in general, the researchers wrote. Inherent disorders of cell-mediated immunity and the high percentage of SLE patients that develop central nervous system (CNS) damage due to autoimmune attack render the blood brain barrier susceptible to invasion from the cryptococcal microbe. 

Cryptococcal meningitis is deadly and is caused by the fungus cryptococcus neoformans/cryptococcus gattii complex. Cryptococcus is an opportunistic infection that takes advantage of the immune compromised patient. Cryptococcal meningitis is the number one cause of invasive fungal death in patients with systemic lupus erythematosus. The researchers stressed that it is of vital importance that rheumatologists familiarize themselves with CM presentation, severity and treatment while not underestimating its prevalence.

Cryptococcal meningitis is ranked as the most important central nervous system infection for SLE patients. It appears that lack of understanding about presentation, prevalence, diagnosis and prevention may be contributing factors that signal a need for a broader dissemination of information about cryptococcal meningitis and lupus. 

While cryptococcal meningitis in the general population typically strikes males, SLE patients are more often females in their 30s, the review found. It was also discovered that cryptococcal meningitis appeared rather early in the course of SLE progression. This underscores the need for rheumatologists to be on the look out for this infection in young, newly diagnosed patients. 

The authors review uncovered an important relationship between higher mortality and high dose steroid therapy. Higher doses of corticosteroids are known to increase the risk of infection and now possibly mortality in patients with SLE and cryptococcal meningitis infections.  Misdiagnosis also hampers efforts to reduce the incidence of cryptococcal meningitis in SLE patients.  More than one third of patients were misdiagnosed largely as a result of failing to sample and test cerebrospinal fluid for fungal pathogens.

Defining the Scope of the Problem

The first step towards diagnosing, treating and preventing CM in SLE patients is defining the scope of the problem. This is a prevalent and deadly infection that is misdiagnosed in a high percentage of cases. Paying close attention to patient complaints and judicious use of corticosteroids coupled with prophylaxis for high risk patients may help reduce mortality related to CM. Utilizing low cost high yield diagnostic tools like india ink microscopy with a high index of suspicion may increase early diagnosis, especially in developing countries. Ultimately these advances must be accompanied by better access to affordable anti-fungals and clinicians on the front lines armed with the facts.

“More emphasis should be placed to further understand lupus-related cryptococcal meningitis and to develop better prophylaxis and management strategies to combat this condition,” researchers wrote.

Takeaways

  • Cryptococcal meningitis is the leading cause of invasive fungal infections in patients with SLE.
  • Cryptococcal meningitis is misdiagnosed over one third of the time as a bacterial infection leading to improper treatment.
  • Nearly one-fourth of in systemic lupus erythematosus patients who contracted cryptococcal meningitis died.
  • Symptoms of cryptococcal meningitis in reviewed patients in order from most to least common:  Headache, fever, nausea, vomiting and neck rigidity.
  • High dose corticosteroid therapy increases the likelihood of death among those with cryptococcal meningitis and systemic lupus erythematosus.

 

References

Fang W, Chen M, Liu J, et al. "Cryptococcal meningitis in systemic lupus erythematosus patients: pooled analysis and systematic review,"  Emerging Microbes & Infections. Sept. 7, 2016. DOI:10.1038/emi.2016.93

http://www.rheumatologynetwork.com/news/cryptococcal-meningitis-infections-lupus-often-misdiagnosed?GUID=&XGUID=&rememberme=1&ts=13102016

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